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Supplemental Digital Content is Available in the Text. High-speed videography of hind paw withdrawal produced variable results across experimenters, did not consistently reflect intensity-dependent pain scores, and did not differentiate inflamed and naive animals. Few analgesics identified using preclinical models have successfully translated to clinical use. These translational limitations may be due to the unidimensional nature of behavioral response measures used to assess rodent nociception. Advances in high-speed videography for pain behavior allow for objective quantification of nuanced aspects of evoked paw withdrawal responses. However, whether videography-based assessments of mechanical hypersensitivity outperform traditional measurement reproducibility is unknown. First, we determined whether high-speed videography of paw withdrawal was reproducible across experimenters. Second, we examined whether this method distinguishes behavioral responses exhibited by naive mice and mice with complete Freund's adjuvant (CFA)-induced inflammation. Twelve experimenters stimulated naive C57BL/6 mice with varying mechanical stimuli. Paw withdrawal responses were recorded with high-speed videography and scored offline by one individual. Our group was unable to replicate the original findings produced by high-speed videography analysis. Surprisingly, ∼80% of variation was not accounted for by variables previously reported to distinguish between responses to innocuous and noxious stimuli (paw height, paw velocity, and pain score), or by additional variables (experimenter, time-of-day, and animal), but rather by unidentified factors. Similar high-speed videography assessments were performed in CFA- and vehicle-treated animals, and the cumulative data failed to reveal an effect of CFA injection on withdrawal as measured by high-speed videography. This study does not support using paw height, velocity, or pain score measurements from high-speed recordings to delineate behavioral responses to innocuous and noxious stimuli. Our group encourages the continued use of traditional mechanical withdrawal assessments until additional high-speed withdrawal measures are validated in established pain models. [ABSTRACT FROM AUTHOR]

Kenta Nakada,1,2 Kazuhiro Shimo,3 Satoshi Ohga,3 Takako Matsubara1,3 1Faculty of Rehabilitation, Kobe Gakuin University Graduate School, Kobe, Japan; 2Department of Rehabilitation, Ikeda Rehabilitation Hospital, Kurobe, Japan; 3Department of Physical Therapy, Faculty of Rehabilitation, Kobe Gakuin University, Kobe, JapanCorrespondence: Kazuhiro Shimo, Department of Physical Therapy, Faculty of Rehabilitation, Kobe Gakuin University, 518 Arise, Ikawadani-cho, Nishi-ku, Kobe, Hyogo, 651-2180, Japan, Tel/Fax +81-78-974-2461, Email shimo@reha.kobegakuin.ac.jpPurpose: This study assessed the pain associated with movement and exercise in older individuals with cognitive decline, using the Abbey Pain Scale (APS) to identify the sub-items that effectively reflect pain during such activities.Patients and Methods: A cross-sectional study was conducted in 225 older patients with musculoskeletal disorders and cognitive decline at the Ikeda Rehabilitation Hospital in Toyama, Japan. Pain during walking or transferring was assessed using the verbal rating scale (VRS) and the APS. Item response theory (IRT) was used to identify the APS sub-items that most accurately reflected the presence and degree of pain.Results: Pain associated with movement scored 1.3 ± 1.1 on the VRS and 2.5 ± 2.6 on the APS. The IRT analysis extracted “vocalization”, “facial expression”, and “change in body language” as the most reliable indicators of pain. These extracted items showed good internal consistency (Cronbach’s α = 0.72), were significantly positively related to changes in the VRS (rs = 0.370, p < 0.001), and showed significant differences between patients with and without subjective pain.Conclusion: Our study suggests that the APS sub-items “vocalization”, “facial expression”, and “change in body language” may be the most effective indicators of pain during movement and exercise in older individuals with cognitive decline. This approach may enhance the reliability of pain assessments and management during exercise therapy.Keywords: behavior observation assessments, pain assessment, pain behavior, item response theory

Abstract Osteoarthritis (OA) is one of the most prevalent chronic musculoskeletal diseases among the elderly population. In this study, macrophage-derived exosomes were isolated and identified. Exosomes were subjected to microRNA (miRNA) sequencing and bioinformatic analysis, and differentially expressed miRNAs were verified. miR-26b-5p target genes were confirmed through target-site mutation combined with a dual-luciferase reporter assay. The effects of miR-26b-5p on macrophage polarization and chondrocyte hypertrophy were assessed in vitro. miR-26b-5p agomir was applied to mice with OA induced by anterior cruciate ligament transection (ACLT). The therapeutic effects of miR-26b-5p were evaluated via pain behavior experiments and histological observations. In vitro, miR-26b-5p repolarized M1 macrophages to an anti-inflammatory M2 type by targeting the TLR3 signaling pathway. miR-26b-5p could target COL10A1, further inhibiting chondrocyte hypertrophy induced by M1 macrophage-conditioned medium (M1-CM). In vivo, miR-26b-5p agomir ameliorated gait abnormalities and mechanical allodynia in OA mice. miR-26b-5p treatment attenuated synovitis and cartilage degeneration, thereby delaying OA progression. In conclusion, M2 macrophage-derived exosomal miR-26b-5p could protect articular cartilage and ameliorate gait abnormalities in OA mice by targeting TLR3 and COL10A1. miR-26b-5p further affected macrophage polarization and chondrocyte hypertrophy. Thus, this exosomal miR-26b-5p-based strategy might be a potential method for OA treatment. Graphical Abstract

Transcutaneous electrical nerve stimulation (TENS) has been used to reduce pain or improve motor function in musculoskeletal and neurological disorders in the clinic. Although some studies have suggested electrotherapy as an intervention for edema, the effects and mechanisms of TENS on inflammation-induced edema remain unclear. Thus, we aimed to investigate the effects of TENS on arthritic pain with edema. 1% carrageenan was injected into the right tibiofemoral joint of 69 male Sprague--Dawley rats (200-250 g). After the development of arthritic pain, low-frequency (4-Hz, Low-TENS, n = 25) and high-frequency (100- Hz, High-TENS, n = 25) TENS with sub-motor threshold or placebo-TENS (n = 19) was applied for 20-min to medio-lateral part of the ipsilateral side. Weight bearing and knee-bend tests were used to assess painlike behaviors. Also, we examined the size of edema and measured tumor necrosis factor-alpha (TNF- α) and interleukin-1 beta (IL-1 β) levels in the synovium by western blot. Eight rats in each of the two TENS groups were injected with Naloxone. Edema was reduced in the low- and high-frequency TENS groups at 6-h. TENS-treated rats showed reduced pain in the knee-bend test at 6-h. We observed decreased weight load shifts on the ipsilateral side in TENS groups. Naloxone reduced these effects. TNF- α and IL-1 β expression decreased in the synovial membrane at 6-h. These results suggest that low- and high-frequency TENS have acutely positive effects on inflammatory edema, with the management of arthritic pain and reduction in pro-inflammatory mediators. Therefore, Low-TENS and High-TENS may be useful in treating acute inflammatory pain and edema. [ABSTRACT FROM AUTHOR]

There is an anecdotal impression that teenage patients report exaggerated postoperative pain scores that do not correlate with their actual level of pain. Nurse and parental perception of teenagers' pain can be complemented by knowledge of patient pain behavior, catastrophizing thoughts about pain, anxiety, and mood level. Two hundred and two patients completed the study—56.4% were female, 89.6% White, 5.4% Black, and 5% were of other races. Patient ages ranged from 11 to 17 years (mean = 13.8; SD = 1.9). The patient, the parent, and the nurse completed multiple questionnaires on day one after laparoscopic surgery to assess patient pain. Teenagers and parents (r = 0.56) have a high level of agreement, and teenagers and nurses (r = 0.47) have a moderate level of agreement on pain scores (p < 0.05). The correlation between patient APBQ (adolescent pain behavior questionnaire) and teenager VAS (visual analog scale) and between nurse APBQ and teenager VAS, while statistically significant (p < 0.05), is weaker (r range = 0.14–0.17). There is a moderate correlation between teenagers' pain scores and their psychological assessments of anxiety, catastrophic thoughts, and mood (r range = 0.26–0.39; p < 0.05). A multi-modal evaluation of postoperative pain can be more informative than only assessing self-reported pain scores. [ABSTRACT FROM AUTHOR]

Background: An experimental study was performed to improve the anterior approach model of intervertebral disc degeneration (IVDD). Objective: The aims of this study were to investigate the anterior approach model of IVDD for the cause of death, phenotypes, and underlying mechanisms of low back pain in mice. Method: In this study, we conducted an anterior puncture procedure on a cohort of 300 C57BL/6J mice that were 8 weeks old. Our investigation focused on exploring the causes of death in the study population (n = 300) and assessing the time‐course changes in various parameters, including radiographical, histological, immunofluorescence, and immunohistochemistry analyses (n = 10). Additionally, we conducted behavioral assessments on a subset of the animals (n = 30). Results: Transverse vertebral artery rupture is a major factor in surgical death. Radiographical analyses showed that the hydration of the nucleus pulposus began to decrease at 2 weeks after puncture and obviously disappeared over 4 weeks. 3D‐CT showed that disc height was significantly decreased at 4 weeks. Osteophyte at the anterior vertebral rims was observed at 2 weeks after the puncture. As the time course increased, histological analyses showed progressive disruption of the destruction of the extracellular matrix and increased secretion of inflammatory cytokines and apoptosis. Behavioral signs of low back pain were increased between the puncture and sham groups at 4 weeks. Conclusion: The improvement of anterior intervertebral disc approach model in mice will be useful to investigate underlying mechanisms and potential therapeutic strategies for behavior and phenotypes. Furthermore, the application of vibrational pre‐treatment can be used to increase the sensitivity of axial back pain in the model, thereby providing researchers with a reliable method for measuring this critical phenotype. [ABSTRACT FROM AUTHOR]

Getu Ataro Hanago,1 Matthias Siebeck,2 Samuel Jilo Dira,3 Tefera Tadesse,4 Dominik Irnich5 1Department of Anesthesia, Hawassa University, Hawassa, Ethiopia; 2Institute of Medical Education, LMU University Hospital, LMU Munich, Munich, Germany; 3Department of Anthropology, Hawassa University, Hawassa, Ethiopia; 4Institute of Educational Research, Addis Ababa University, Addis Ababa, Ethiopia; 5Multidiciplinary Pain Center, Department of Anesthesiology, LMU University Hospital LMU Munich, Munich, GermanyCorrespondence: Getu Ataro Hanago, Email getsha@yahoo.comBackground: Despite its universal nature; perception, coping, responses, treatment options, and overall experiences of pain are influenced by biopsychosocial factors to various extents. Pain perception, expression, and control are progressively learned behaviors among members of a society and are culture-specific. Effects of ethnicity-related culture (ethnoculture) on pain experience in a broader context have increasingly been reported. However, evidence from ethnoculturally diverse groups of a nation, particularly based on surgical patients, is limited. Therefore, as a qualitative research effort of a broader project aimed at assessing ethnocultural determinants of surgical pain management, this study explored the perception of ethnoculturally diverse patients and families about expressing surgical disease-related pain.Methods: This study follows subjectivist-interpretivist philosophical assumptions as an underpinning research paradigm. We purposively selected 11 patients for in-depth interviews and 12 patients’ family members for focus group discussions in three hospitals of ethnic-based regions of Ethiopia. In the phenomenological frame, thematic analysis was employed.Finding: Ethnocultural background influences how individuals express and respond to pain according to emergent themes of finding— Pain and overlooked cultural influence, Pain expressiveness in cultural context, Stereotypes of pain expressiveness, and Bravehood through stoic response. Pain feelings are commonly hidden where the domestic culture values stoic response to pain compared to ethnoculture where pain expressiveness is encouraged.Conclusion: Individuals can express and respond to pain differently due to ethnocultural diversity within a nation. Researchers and clinicians should consider cultural context while applying the prevailing one-size-fits-all pain assessment tools among surgical patients of a nation with ethnocultural diversity.Keywords: surgical pain, pain and culture, pain expression, pain behavior, pain response, stoic response

Introduction: The factors that mediate the expression of ocular pain and the mechanisms that promote chronic ocular pain symptoms are poorly understood. Central nervous system involvement has been postulated based on observations of pain out of proportion to nociceptive stimuli in some individuals. This investigation focused on understanding functional connectivity between brain regions implicated in chronic pain in persons reporting ocular pain symptoms. Methods: We recruited a total of 53 persons divided into two cohorts: persons who reported no ocular pain, and persons who reported chronic ocular pain, irrespective of ocular surface findings. We performed a resting state fMRI investigation that was focused on subcortical brain structures including the trigeminal nucleus and performed a brief battery of ophthalmological examinations. Results: Persons in the pain cohort reported higher levels of pain symptoms relating to neuropathic pain and ocular surface disease, as well as more abnormal tear metrics (stability and tear production). Functional connectivity analysis between groups evinced multiple connections exemplifying both increases and decreases in connectivity including regions such as the trigeminal nucleus, amygdala, and sub-regions of the thalamus. Exploratory analysis of the pain cohort integrating clinical and brain function metrics highlighted subpopulations that showed unique phenotypes providing insight into pain mechanisms. Discussion: Study findings support centralized involvement in those reporting ocular-based pain and allude to mechanisms through which pain treatment services may be directed in future research. [ABSTRACT FROM AUTHOR]

Abstract Background An experimental study was performed to improve the anterior approach model of intervertebral disc degeneration (IVDD). Objective The aims of this study were to investigate the anterior approach model of IVDD for the cause of death, phenotypes, and underlying mechanisms of low back pain in mice. Method In this study, we conducted an anterior puncture procedure on a cohort of 300 C57BL/6J mice that were 8 weeks old. Our investigation focused on exploring the causes of death in the study population (n = 300) and assessing the time‐course changes in various parameters, including radiographical, histological, immunofluorescence, and immunohistochemistry analyses (n = 10). Additionally, we conducted behavioral assessments on a subset of the animals (n = 30). Results Transverse vertebral artery rupture is a major factor in surgical death. Radiographical analyses showed that the hydration of the nucleus pulposus began to decrease at 2 weeks after puncture and obviously disappeared over 4 weeks. 3D‐CT showed that disc height was significantly decreased at 4 weeks. Osteophyte at the anterior vertebral rims was observed at 2 weeks after the puncture. As the time course increased, histological analyses showed progressive disruption of the destruction of the extracellular matrix and increased secretion of inflammatory cytokines and apoptosis. Behavioral signs of low back pain were increased between the puncture and sham groups at 4 weeks. Conclusion The improvement of anterior intervertebral disc approach model in mice will be useful to investigate underlying mechanisms and potential therapeutic strategies for behavior and phenotypes. Furthermore, the application of vibrational pre‐treatment can be used to increase the sensitivity of axial back pain in the model, thereby providing researchers with a reliable method for measuring this critical phenotype.

IntroductionThe factors that mediate the expression of ocular pain and the mechanisms that promote chronic ocular pain symptoms are poorly understood. Central nervous system involvement has been postulated based on observations of pain out of proportion to nociceptive stimuli in some individuals. This investigation focused on understanding functional connectivity between brain regions implicated in chronic pain in persons reporting ocular pain symptoms.MethodsWe recruited a total of 53 persons divided into two cohorts: persons who reported no ocular pain, and persons who reported chronic ocular pain, irrespective of ocular surface findings. We performed a resting state fMRI investigation that was focused on subcortical brain structures including the trigeminal nucleus and performed a brief battery of ophthalmological examinations.ResultsPersons in the pain cohort reported higher levels of pain symptoms relating to neuropathic pain and ocular surface disease, as well as more abnormal tear metrics (stability and tear production). Functional connectivity analysis between groups evinced multiple connections exemplifying both increases and decreases in connectivity including regions such as the trigeminal nucleus, amygdala, and sub-regions of the thalamus. Exploratory analysis of the pain cohort integrating clinical and brain function metrics highlighted subpopulations that showed unique phenotypes providing insight into pain mechanisms.DiscussionStudy findings support centralized involvement in those reporting ocular-based pain and allude to mechanisms through which pain treatment services may be directed in future research.

Objective: Acute pain is the most common type of pain. The aim of the present work was carried out to study the antinociceptive effect and pharmacological mechanisms of thiocyanoacetamide (Thm) in rats exposed to thermal pain stimulus. Materials and Methods: The anti‐nociceptive effect of the newly synthesized compound, Thm was studied in comparison to that of paracetamol (Para), dexamethasone (Dex), and morphine (Morph) at different doses using a hot plate test at a constant temperature of 48.0 ± 0.5°C. During this test, the latency time (LT) was measured when rats express pain behavior. Then, the pharmacological mechanisms were determined using receptor‐antagonist drugs. Results: Firstly, the obtained result showed pain modulation of the pretreated rats with Thm at 10 mg/kg dose proved by the delay of latency time during the thermal test. This significant antinociceptive activity of the thiocyanoacetamide was more effective than that of paracetamol or dexamethasone and less than that of morphine. Second, the pretreatment with acebutolol or risperidone antagonist drugs of, respectively, adrenergic and serotonin receptors demonstrated the elimination of pain modulation with Thm 10 mg/kg dose proved by a short latency time of rat's response in hot plate test. In this case, the pharmacological mechanism of Thm was characterized by the involvement of adrenergic and serotoninergic systems. Conclusions: It may be concluded that Thm constitutes a promising antinociceptive drug including beta‐adrenergic and serotoninergic targets. The present study warrants further investigation to determine the side effects of this compound. [ABSTRACT FROM AUTHOR]

Context: Low back pain ( LBP) is a serious health problem, both in the general population as well as in athletes. Research has shown that psychosocial aspects, such as dysfunctional pain responses, play a significant role in the chroni fication of LBP. Recent research supports the relevance of the multidisciplinary concept of body image in the interpretation of LBP. Objective: To examine the differences in 2 psychosocial aspects, body image and pain responses, between athletes and nonathletes with LBP. Design: Cross - sectional design. Setting: The questionnaires were distributed in the course of LBP treatment . Participants. Data from 163 athletes (mean age = 28 .69 [ 9 . 61 y ) and 75 nonathletes (mean age = 39 . 34 [ 12 . 631 y ) were collected. Interventions: Data were collected by questionnaires assessing body image, pain behavior, training activity, and LBP . Main Outcome Measures : To examine group differences between athletes and nonathletes regarding body image and pain behavion the authors performed 2-way analyses of variance with Bonferroni post hoc tests. Results: The results showed (1) a significant main effect regarding pain responses and body image, showing that participants with eustress endurance or adaptive pain behavior revealed a more positive body image in both groups compared with participants with distress endurance or fear-avoidance behavior. and (2) a significant main effect for the factor group in the body image dimension of physical efficacy, indicating a more positive body image for athletes. Conclusion: These results suggest that considering multiple risk factors for LBP, such as body image and dysfunctional pain behavior, as well as subgrouping, might be valuable for research and for broadening therapy options. [ABSTRACT FROM AUTHOR]

There is an anecdotal impression that teenage patients report exaggerated postoperative pain scores that do not correlate with their actual level of pain. Nurse and parental perception of teenagers’ pain can be complemented by knowledge of patient pain behavior, catastrophizing thoughts about pain, anxiety, and mood level. Two hundred and two patients completed the study—56.4% were female, 89.6% White, 5.4% Black, and 5% were of other races. Patient ages ranged from 11 to 17 years (mean = 13.8; SD = 1.9). The patient, the parent, and the nurse completed multiple questionnaires on day one after laparoscopic surgery to assess patient pain. Teenagers and parents (r = 0.56) have a high level of agreement, and teenagers and nurses (r = 0.47) have a moderate level of agreement on pain scores (p < 0.05). The correlation between patient APBQ (adolescent pain behavior questionnaire) and teenager VAS (visual analog scale) and between nurse APBQ and teenager VAS, while statistically significant (p < 0.05), is weaker (r range = 0.14–0.17). There is a moderate correlation between teenagers’ pain scores and their psychological assessments of anxiety, catastrophic thoughts, and mood (r range = 0.26–0.39; p < 0.05). A multi-modal evaluation of postoperative pain can be more informative than only assessing self-reported pain scores.

Arthritic disorders have become one of the main contributors to the global burden of disease. Today, they are one of the leading causes of chronic pain and disability worldwide. Current therapies are incapable of treating pain sufficiently and preventing disease progression. The lack of understanding basic mechanisms underlying the initiation, maintenance and progression of arthritic disorders and related symptoms represent the major obstacle in the search for adequate treatments. For a long time, histological evaluation of joint pathology was the predominant outcome parameter in preclinical arthritis models. Nevertheless, quantification of pain and functional limitations analogs to arthritis related symptoms in humans is essential to enable bench to bedside translation and to evaluate the effectiveness of new treatment strategies. As the experience of pain and functional deficits are often associated with altered gait behavior, in the last decades, automated gait analysis has become a well-established tool for the quantitative evaluation of the sequalae of arthritic disorders in animal models. The purpose of this review is to provide a detailed overview on the current literature on the use of the CatWalk gait analysis system in rodent models of arthritic disorders, e.g., Osteoarthritis, Monoarthritis and Rheumatoid Arthritis. Special focus is put on the assessment and monitoring of pain-related behavior during the course of the disease. The capability of evaluating the effect of distinct treatment strategies and the future potential for the application of the CatWalk in rodent models of arthritic disorders is also addressed in this review. Finally, we discuss important consideration and provide recommendations on the use of the CatWalk in preclinical models of arthritic diseases.

Background: The Pain Behavioral Scale (PaBS) measures the presence and severity of pain behavior. We examine the longitudinal construct validity of the PaBS using convergent and known-groups approaches on a population of 23 participants with chronic lower back pain (LBP) undergoing routine physiotherapy care and pain neuroscience education. Methods: Participants who satisfied study inclusion and exclusion criteria were recruited from patients who attended two testing sessions at physiotherapy clinics in Saudi Arabia. Participant pain behavior was initially measured using the PaBS scale; participants performed standardized physical tests (e.g., repeated trunk flexion) and provided baseline demographic, clinical data, and self-reported measurements using the Modified Roland and Morris disability questionnaire (MODI), fear-avoidance questionnaire (FABQ), and pain catastrophizing scale (PCS). In subsequent visits, a physiotherapist provided usual care to participants, and weekly sessions were established for online pain-neuroscience education. During week six, participants repeated the same questionnaires and physical performance tests with the PaBS. Paired t-tests are used to compare changes in health characteristics from baseline responses to those in week six. Correlations between changes in PaBS from baseline to week six, with changes in outcome measures (i.e., disability, pain intensity, fear-avoidance beliefs, catastrophizing), were determined. To assess known-group validity, we also used a general linear model. Results: A total of 23 participants completed the PNE and follow-up data collection. The mean change from baseline in the PaBS score was statistically significant, as were changes in MODI, FABQ, and PCS. Almost 70% of participants improved their PaBS scores over the six-week period, with PaBS scores of almost 40% of them improving by three units or more. The change in PaBS score correlated significantly with changes in the PCS-rumination subscale, supporting a proposed approach to estimate convergent validity (r = 0.44, 95% CI = 0.04–0.72, p = 0.035). Conclusions: The mean change from baseline in the PaBS score is statistically significant, as are changes in MODI, FABQ, and PCS, supporting its convergent validity. According to our STarT Back groups, the medium to low-risk group had a lower PaBS score, and high-risk group had a higher PaBS score, indicating that PaBS use in clinical assessment may identify people according to pain-behavior severity, or those at increased risk of developing disability. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Persistent idiopathic facial pain (PIFP) and attention‐deficit/hyperactivity disorder (ADHD) may coexist and can be improved with ADHD medications. Thus, clinicians should screen for ADHD by a multidisciplinary approach when treating PIFP and differentiate between other odontogenic disorders. We report a case of a woman with persistent idiopathic facial pain (PIFP) and attention‐deficit/hyperactivity disorder (ADHD) that markedly improved with the administration of a combination of aripiprazole (APZ) and methylphenidate (MP) treatment. Screening for ADHD and administration of APZ and/or MP may be considered in treating PIFP. [ABSTRACT FROM AUTHOR]

Serotonin (5-hydroxytryptamine, 5-HT) released by platelets, mast cells, and immunocytes is a potent inflammatory mediator which modulates pain and itch sensing in the peripheral nervous system. The serotonergic receptors expressed by primary afferent neurons involved in these sensory functions are not fully identified and appear to be to a large extent species dependent. Moreover, the mechanisms through which 5-HT receptor activation is coupled to changes in neuronal excitability have not been completely revealed. Using a combination of in vitro (calcium and voltage imaging and patch-clamp) and in vivo behavioral methods, we used both male and female Wistar rats to provide evidence for the involvement of two 5-HT receptor subtypes, 5-HT1A and 5-HT3, in mediating the sustained and transient effects, respectively, of 5-HT on rat primary afferent neurons involved in pain and itch processing. In addition, our results are consistent with a model in which sustained serotonergic responses triggered via the 5-HT1A receptor are due to closure of background potassium channels, followed by membrane depolarization and action potentials, during which the activation of voltage-gated calcium channels leads to calcium entry. Our results may provide a better understanding of mammalian serotonergic itch signaling.

ObjectiveTo establish a rat hyperalgesia model of acute pulpitis induced by lipopoly-saccharide (LPS) administration to the maxillary molars. In addition, to analyze and evaluate the acute pain and LPS-induced pulpitis, and to investigate the change of pain threshold in rats with acute pulpitis.MethodsForty-five adult male Sprague-Dawley (SD) rats were equally divided into LPS group, normal saline (NS) group, and blank control (SHAM) group, with 15 rats in each group. Under isoflurance anesthesia, the rats in the LPS group had their right upper molar teeth drilled and LPS was sealed temporarily with Caviton, while those in the NS group had their right upper molar teeth drilled and normal saline was sealed temporarily with Caviton. Rats in the SHAM group, serving as blank control group,were only anesthetized with isoflurane. Pain behavioral indexes, including spontaneous pain behavior scores, 50% paw withdrawal threshold (PWT), head withdrawal thresholds (HWT), paw withdrawal latency (PWL), and head withdrawal latency (HWL) were measured before and 2 h, 24 h, 48 h, and 72 h after surgery. After rats were anesthetized and sacrificed, the pathological status of pulp tissues was confirmed with hematoxylin-eosin staining and pathological examination and serum IL-1β and TNF-α were determined by ELISA.ResultsConcerning spontaneous pain behavior, the facial grooming time in the LPS group was significantly higher than that in the NS group postoperatively (P＜0.05), and increased gradually with time, although there was no significant difference in activity time. The HWT in the LPS group was significantly lower than that in the NS group at 2 h, 24 h, and 48 h postoperatively (P＜0.05). Additionally, 50% PWT in the LPS and NS groups were significantly lower than those in the SHAM group (P＜0.05). The LPS group had a significantly lower HWL than the NA group at 2 h and 48 h postoperatively (P＜0.05). Likewise, the PWL was significantly lower in the LPS group than the NS group (P＜0.05) at 72 h postoperatively. The IL-1β and TNF-α levels in the rats’ serum were significantly higher in the LPS group than in the NS group (P＜0.01 or P＜0.05). Moreover, the IL-1β and TNF-α levels in all groups began increasing 2 h after the model establishment, reaching a peak at 48 h. The pathological results of the LPS group showed a gradual expansion in the neutrophil infiltration area from the point of perforation to the crown pulp and upper root pulp, in 24-72 h after modeling. The rats in the NS group exhibited milder degree of inflammation than those in the LPS group.ConclusionBased on the observations regarding rat behavior, pathological changes of dental pulp, and detection of inflammatory factors in serum, the LPS induced acute pulpitis model causes pathological pain and pain threshold alterations in rats.

Inflammatory pain is part of the body's defense mechanism and plays an important role in the healing process. Although some drugs are efficient and intensively used for their potent anti-inflammatory properties, they present problematic side effects. The aim of this study was to evaluate the anti-nociceptive effect of the thiocyanoacetamide (Thm) compared to paracetamol (Para), dexamethasone (Dex) and morphine (Morph) and to study inflammatory mediators on models of acute inflammatory pain in rats using the formalin injection test in the hind paw of rats as chemical stimulus. The obtained results showed significant modulation of pain by Thm pretreatment with a maximum at an effective dose (10 mg/kg) proved by the absence of licking and biting of the affected paw during the early and late phases of inflammation. This effect was comparable to Dex at 10 mg/kg, Para at 400 mg/kg and less than Morph at 5 mg/kg pretreatment doses. The study of anti-inflammatory targets showed that Thm pretreatment maintained plasma serotonin release at normal level compared to the negative control group (T−) and corrected the decrease in the plasma level of prostaglandins after inflammatory induction with no variation in the level of histamine in different groups. The evaluation of inflammation mediators demonstrated that the pretreatment with Thm induced the decrease in the amount of both IL-1 Beta and TNF alpha in plasma and the increase in their amount in the tissue of the injection site. The Thm has been promoted as an anti-nociceptive drug that induces modulation of inflammatory mediators. [ABSTRACT FROM AUTHOR]

To investigate the effects of matrine on P2X3 receptor, pain behavior and pain threshold in neuropathic rat dorsal root ganglion. Thirty Sprague-Dawley male rats were randomly divided into 3 groups, including model group, experimental group and sham operation group. One day after successful modeling, the experimental group was given 30 mg/ (kgod) intraperitoneal injection of matrine solution, once a day; Sham operation group and model group were given intraperitoneal injection of 0.9% sodium chloride solution once a day for 14 days. Spontaneous pain behavioral score, mechanical pain threshold, thermal pain threshold, P2X2 and P2X3mRNA relative expression levels, P2X2 and P2X3 protein expression levels, and oxidative stress index levels were detected. The scores of spontaneous pain behavior in both the model group and the experimental group were higher than those in the sham operation group. Since the 5th day after surgery, the scores of spontaneous pain behavior in the experimental group were lower than those in the model group(P<0.05). Compared with the sham operation group, the mechanical pain threshold and thermal pain threshold in the model group were decreased from the 3rd day after surgery, while the mechanical pain threshold and thermal pain threshold in the experimental group were increased from the 5th day after surgery (all P<0.05). There were no differences in mechanical pain threshold and thermal pain threshold between experimental group and sham operation group on day 14 after surgery (P>0.05). P2X2 and P2X3 mrna, P2X2 and P2X3 proteins in model group were higher than those in sham operation group and experimental group (P<0.05), but there were no differences in P2X2, P2x3 mRNA, P2X2 and P2x3 proteins between experimental group and sham operation group (P>0.05). SOD and MDA of spinal cord in model group were lower and higher than those in sham group before intervention and 1 and 2 weeks after intervention. SOD and MDA of spinal cord tissue of experimental group were higher than those of model group (all P<0.05). Matrine can effectively relieve mechanical and thermal pain induced by neuropathic pain, and has good analgesic effect. The mechanism may be that matrine can reduce P2X2 and P2X3 receptors in dorsal root neurons of rats, and it also plays a role in inhibiting oxidative stress response of spinal cord tissue of neuropathic rats. It is closely related to the inhibition of neuronal apoptosis in spinal cord of neuropathic pain rats. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Mice were tested for pain after injury until death. Sex differences were observed in pain behavior over time and in the relationship between pain and lifespan. Human epidemiological studies suggest that chronic pain can increase mortality risk. We investigated whether this was true in mice so that underlying mechanisms might be identified. At 10 weeks of age, C57BL/6 mice of both sexes received sham or spared nerve injury (SNI) surgery producing neuropathic pain. Mice were weighed monthly, tested behaviorally for mechanical and cold sensitivity and guarding behavior every 3 months postsurgery, and otherwise left undisturbed in their cages until death by natural causes. Evidence of pain over the lifespan displayed a strikingly sex-specific pattern. Male mice displayed largely stable mechanical and cold hypersensitivity and guarding at 6 to 30 months post-SNI. By contrast, female mice displayed a biphasic temporal pattern of mechanical hypersensitivity and guarding behavior, with a complete resolution of SNI-induced pain behavior at 6 to 9 months post-SNI followed by the return of pain thereafter. Mouse lifespan was not significantly altered by SNI in either sex nor was frailty as assessed by cage inspection in the last 6 months of life. However, in male mice with SNI, we observe a significant correlation between average lifetime mechanical hypersensitivity and lifespan, such that death occurred sooner in male mice exhibiting more evidence of chronic pain. This relationship was not observed in female SNI mice nor in sham-operated mice of either sex. This experiment is the first to investigate pain behavior over an entire adult lifetime and suggests that biology of relevance to human chronic pain is being ignored by the very short timespans of most extant preclinical pain research. [ABSTRACT FROM AUTHOR]

Key Clinical Message Persistent idiopathic facial pain (PIFP) and attention‐deficit/hyperactivity disorder (ADHD) may coexist and can be improved with ADHD medications. Thus, clinicians should screen for ADHD by a multidisciplinary approach when treating PIFP and differentiate between other odontogenic disorders. Abstract We report a case of a woman with persistent idiopathic facial pain (PIFP) and attention‐deficit/hyperactivity disorder (ADHD) that markedly improved with the administration of a combination of aripiprazole (APZ) and methylphenidate (MP) treatment. Screening for ADHD and administration of APZ and/or MP may be considered in treating PIFP.

Background and aim: Osteoarthritis (OA) is characterized by pain and inflammation. Electroacupuncture (EA) and swimming (SW) are non-pharmacological interventions recommended for treating OA. The study evaluated the benefits of electroacupuncture (EA) and swimming (SW) association when compared with isolated protocols in an OA rodent model. Experimental. Procedures: An ankle monoarthritis model was induced in rats by applying Complete Freund's Adjuvant (CFA). After seven days of induced OA, the groups were submitted to EA (ST36 and the GB 30 Acupoint), SW, or the EA + SW protocol. The nociceptive behavior was measured by the Von Frey test, the Cold Stimulation test, and the Paw Flick Immersion test. Inflammatory activity was evaluated by measuring TNF levels, myeloperoxidase, NAGase, immunological parameters and the histology from the subcutaneous tissue. Results: Compared to CFA group, EA decreased the nociceptive scores in the cold stimulation test (p

PURPOSE:To elucidate the effects of growth differentiation factor-6 (GDF6) on: (i) gene expression of inflammatory/pain-related molecules and structural integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii) sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia (DRGs) in the rat xenograft radiculopathy model. METHODS:Forty-six adolescent rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 µg) was injected into the nucleus pulposus (NP) of punctured discs and followed for 4 weeks for gene expression analysis and 12 weeks for structural analyses. For pain assessment, eight rabbits were sacrificed at 4 weeks post-injection and NP tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically. RESULTS:In GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, prostaglandin-endoperoxide synthase 2, and nerve growth factor were significantly lower than those in the PBS group. GDF6 injections resulted in partial restoration of disc height and improvement of MRI disc degeneration grades with statistical significance in rabbit structural analyses. Allodynia induced by xenograft transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced by GDF6 injection. Staining intensities for ionized calcium-binding adaptor molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were significantly lower than those of the PBS group. CONCLUSION:GDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.

Abstract: The experience of pain and pain behaviors is not only determined by physiological but also psychosocial factors. In this context, the learning history of the individual and specifically operant reinforcement related to spouse responses might play an important role. We investigated the effect of a solicitous and habitually pain-reinforcing spouse for the processing of pain in patients with chronic pain. Using multichannel electroencephalography, pain behaviors, and self-reports of pain, we examined 20 patients with chronic back pain (10 with solicitous and 10 with nonsolicitous spouses) and 10 matched healthy controls. The participants received a series of painful and nonpainful electrical stimuli applied to the site of pain (back) and a control area (finger) in the presence vs absence of the spouse. The global field power of the electroencephalogram with a focus in the frontal region was enhanced in patients with chronic back pain who had a solicitous spouse compared to those with a nonsolicitous spouse and the healthy controls. This was specific for the painful stimulation at the back and occurred only in the presence but not the absence of the spouse. Pain ratings of intensity and unpleasantness were also higher in the patients with solicitous spouses when the spouse was present during painful stimulation. These data suggest that significant other responses indicative of operant reinforcement may have a direct effect on the cerebral processing of pain and related pain perception. [ABSTRACT FROM AUTHOR]

The study was conducted in a descriptive type to evaluate the pain behavior and hemodynamic parameters during aspiration of intubated and mildly sedatized patients in the intensive care unit. The study sample consisted of 100 intubated and sedatized patients who were hospitalized in the Anesthesia Intensive Care Unit of Harran University Faculty of Medicine Hospital between February 2018 and June 2018. "Patient Information Form", "Hemodynamic Parameter Form", "Behavioral Pain Scale (BPS)", "Ramsay Sedation Scale" and "Glasgow Coma Scale (GCS)" were used to collect the data. There is a significant difference between the BPS total and subscale scores, mean "systolic and diastolic blood pressure", "heart rate", "respiratory rate" and "SpO2" before, during and after aspiration (p=0.0001), it was determined that the difference was due to the average score after aspiration (p=0.0001). While the SpO2 averages of intubated and sedatized intensive care patients decrease during aspiration, the averages of the BPS scores and other hemodynamic parameters increase. [Med-Science 2021; 10(3.000): 798-803]

Background: The Pain Behavioral Scale (PaBS) measures the presence and severity of pain behavior. We examine the longitudinal construct validity of the PaBS using convergent and known-groups approaches on a population of 23 participants with chronic lower back pain (LBP) undergoing routine physiotherapy care and pain neuroscience education. Methods: Participants who satisfied study inclusion and exclusion criteria were recruited from patients who attended two testing sessions at physiotherapy clinics in Saudi Arabia. Participant pain behavior was initially measured using the PaBS scale; participants performed standardized physical tests (e.g., repeated trunk flexion) and provided baseline demographic, clinical data, and self-reported measurements using the Modified Roland and Morris disability questionnaire (MODI), fear-avoidance questionnaire (FABQ), and pain catastrophizing scale (PCS). In subsequent visits, a physiotherapist provided usual care to participants, and weekly sessions were established for online pain-neuroscience education. During week six, participants repeated the same questionnaires and physical performance tests with the PaBS. Paired t-tests are used to compare changes in health characteristics from baseline responses to those in week six. Correlations between changes in PaBS from baseline to week six, with changes in outcome measures (i.e., disability, pain intensity, fear-avoidance beliefs, catastrophizing), were determined. To assess known-group validity, we also used a general linear model. Results: A total of 23 participants completed the PNE and follow-up data collection. The mean change from baseline in the PaBS score was statistically significant, as were changes in MODI, FABQ, and PCS. Almost 70% of participants improved their PaBS scores over the six-week period, with PaBS scores of almost 40% of them improving by three units or more. The change in PaBS score correlated significantly with changes in the PCS-rumination subscale, supporting a proposed approach to estimate convergent validity (r = 0.44, 95% CI = 0.04–0.72, p = 0.035). Conclusions: The mean change from baseline in the PaBS score is statistically significant, as are changes in MODI, FABQ, and PCS, supporting its convergent validity. According to our STarT Back groups, the medium to low-risk group had a lower PaBS score, and high-risk group had a higher PaBS score, indicating that PaBS use in clinical assessment may identify people according to pain-behavior severity, or those at increased risk of developing disability.

Abstract Background Cognitive-affective factors influence the perception of pain and disability. These factors can lead to pain behaviors (PB) that can persist and become maladaptive. These maladaptive PB will further increase the risk of chronicity or persistence of symptoms and disability. Thus, clinicians must be prepared to recognize maladaptive PB in a clinical context. To date, in the context of assessment in a rehabilitation setting, PB in clinical settings are poorly documented. The main objective of this study was to identify direct observation methods and critically appraise them in order to propose recommendations for practice. As a secondary objective, we explored and extracted the different observable PB that patients could exhibit and that clinicians could observe. Methods We conducted a comprehensive review on four databases with a generic search strategy in order to obtain the largest range of PB. For the first objective, a two-step critical appraisal used clinical criteria (from qualitative studies on barriers to implement routine measures) and psychometric criteria (from Brink and Louw critical appraisal tool) to determine which observation methods could be recommended for clinical practice. For the second objective, we extracted PB found in the literature to list potential PB that patients could exhibit, and clinicians could observe. Results From the 3362 retrieved studies, 47 met the inclusion criteria for the first objective. The clinical criteria allowed us to select three observation methods. After the psychometric step, two observation methods were retained and recommended for clinical practice: the Behavioral Avoidance Test-Back Pain (BAT-Back) and the Pain Behaviour Scale (PaBS). For the second objective, 107 studies met the inclusion criteria. The extraction of the PB allowed us to list a large range of PB and classify the data in 7 categories of PB. Conclusion Our results allowed us to recommend two observation methods for clinical practice. However, these methods have limitations and are validated only in chronic low back pain populations. With the extraction of PB presented in the literature, we contribute to better prepare clinicians to recognize PB in all patients who are experiencing pain.

Abstract Background Although the tearing of tissues during castration is forbidden in the EU, it is still routinely applied in many countries. The goal of this study was to evaluate vocalizations and movements of male piglets undergoing castration by applying different techniques and pain treatments based on scores under practical conditions (Trial 1, n = 50) and to investigate anatomical features after castration of dead piglets with different techniques (Trial 2, n = 28). Results In Trial 1, treatment groups did not significantly influence the duration of castration. Both the duration of vocalization and the scores for vocalizations and movements were lower in piglets castrated under general anesthesia (P

Abstract: Despite tremendous efforts to increase the reliability of pain measures and other self-report instruments, improving or even evaluating the reliability of change scores has been largely neglected. In this study, we investigate the ability of 2 instruments from the Patient-Reported Outcomes Measurement Information System, pain interference (6 items) and pain behavior (7 items), to reliably detect individual changes in pain during the postsurgical period of a hernia repair in 98 patients who answered daily diaries over almost 3 weeks after surgery. To identify the most efficient strategy for obtaining sufficiently reliable estimates of change (reliability >0.9), the number of measurement occasions over the study period (sampling density), the number of items (test length), and the mode of administration (ie, static short form vs Computer adaptive testing) were manipulated in post-hoc simulations. Reliabilities for different strategies were estimated by comparing the observed change with the best approximation of "real" (ie, latent) change. We found (1) that near perfect reliability can be achieved if measures from all days over the whole study period, obtained with all pain interference or pain behavior items, were used to estimate the observed change, (2) that various combinations of the number of items and the number of measurement occasions could achieve acceptable reliability, and (3) that computer adaptive testings were superior to short forms in achieving sufficient reliability. We conclude that the specific strategy for assessing individual postoperative change in pain experience must be selected carefully. [ABSTRACT FROM AUTHOR]

Background Context: Low back pain is one of the most common musculoskeletal disorders. Although, the pathology of intervertebral disc (IVD) degeneration has been modeled using various biological methods, these models are inadequate for simulating similar pathologic states in humans.Purpose: This study investigated whether monosodium iodoacetate (MIA) injection into the IVD of rats could generate a reliable model of IVD degeneration.Study Design/settings: In vivo animal study.Methods: MIA was injected into two-disc spaces (L4-5 and L5-6) of Sprague-Dawley rats. Their behaviors were examined by measuring weight load shifts from hind to forefoot, rearing, and von Frey tests. We examined the inhibition of pain behavior through intraperitoneal morphine injection and measured cyclooxygenase-2 (COX-2) and transcription factor nuclear factor-kappa B (NF-κB) levels in the IVD and dorsal root ganglion (DRG) by Western blot. Bone alterations were assessed by microfocus computed tomography (micro-CT), and IVD and/or cartilage changes were evaluated by hematoxylin and eosin and safranin-O staining and inducible nitric oxide synthase (iNOS) immunohistochemistry. The other authors declare no conflicts of interest. This project funded by the Memorial Fund and the National Research Foundation of Korea (NRF).Results: We observed increased weight load shifts to the forefoot and decreased rearing. Morphine-injected rats showed reduced pain. NF-κB and COX-2 expression increased in the IVD and left and/or right DRG. Micro-CT analyses suggested progressive bone deformation. Histologic examination showed decreased IVD width and nucleus pulposus area. Cartilaginous changes indicated epiphyseal growth plate loss. Finally, iNOS expression was increased in the subchondral endplate.Conclusions: These results suggest that low back pain (LBP) models can be developed by MIA injection into the IVDs of rats and that an animal model is useful for exploring degenerative alterations in the affected discs. Therefore, MIA injection may be a useful model for the study of changes in the IVD to elucidate the mechanisms underlying clinical symptoms, such as LBP, in patients with IVD degeneration.Clinical Significance: This model in which MIA was injected into the disc better represented the human histologic and behavioral characteristics than the existing puncture model. [ABSTRACT FROM AUTHOR]

Many male dairy calves are castrated when reared for beef production, but for dairy breeds the assessment of the longer-lasting pain associated with this procedure has received little scientific attention. In this study we assessed 2 methods: surgical (n = 10 calves) and rubber ring (n = 11). All calves were castrated at 28 d of age using multimodal pain control. During the 8 wk that followed, we recorded wound healing, local inflammation, body weight, milk and calf starter intake, lying time, and wound-directed behavior. Surgical wounds were fully healed on average 4 wk after the procedure, but only 1 calf in the rubber ring treatment fully healed within the 8-wk study. Inflammation was greater after rubber ring castration; skin temperature in the area around the lesion was 1.7 ± 0.35°C (mean ± standard deviation) higher than for the surgical treatment. Compared with surgically castrated calves, those castrated by rubber ring gained less weight over the study period (on average 11.9 ± 5.1 kg less), a difference due in part to lower intake of calf starter (on average 1.8 ± 0.6 kg less). Calves in the rubber ring treatment spent less time lying down (on average 4.2 ± 1.2% fewer scans per day) and licked their lesions more frequently (on average 16.0 ± 3.3 more licks per day). We conclude that the rubber ring calves experienced more pain in the weeks following the procedure and thus recommend that surgical castration be favored for preweaning dairy calves. [ABSTRACT FROM AUTHOR]

Background: Although the tearing of tissues during castration is forbidden in the EU, it is still routinely applied in many countries. The goal of this study was to evaluate vocalizations and movements of male piglets undergoing castration by applying different techniques and pain treatments based on scores under practical conditions (Trial 1, n = 50) and to investigate anatomical features after castration of dead piglets with different techniques (Trial 2, n = 28). Results: In Trial 1, treatment groups did not significantly influence the duration of castration. Both the duration of vocalization and the scores for vocalizations and movements were lower in piglets castrated under general anesthesia (P < 0.05). Behavior scores in conscious piglets did not differ. The incision and extraction caused lower vocalizations and movements than the pulling and severing of spermatic cords (P < 0.01). Movements were more intense during tearing of the spermatic cords than during cutting at the first and second severing (P < 0.01). In both trials, the remains of spermatic cords protruded tendentially more often from castration wounds after severing by tearing (P < 0.09). In Trial 2, the minimum, mean and maximum lengths of the testicles and spermatic cords were extended when severing was realized by tearing (P < 0.01). The mean relative testicle weight of 1.05‰ in dead piglets castrated by tearing was larger than that in dead piglets castrated by cutting (0.91‰) (P < 0.05). Conclusions: The trials uncovered significant differences between behavior expressed by piglets castrated by tearing or cutting, indicating a higher pain level in the tearing group. It was found that the castration technique tearing increased the amount of removed tissues and might cause intraabdominal damage to the remaining tissues and vessels in a yet unknown dimension. These findings should be considered for implementation and stricter enforcement of the ban on tearing for castration. [ABSTRACT FROM AUTHOR]

Pain invalidation involves the dismissal or lack of understanding of another's pain, undermining their subjective experience. Frequent exposure to invalidation negatively impacts mental and physical health as well as pain-related behaviors, potentially leading people to conceal their pain from others in the future and/or withdraw from potential sources of support. It is therefore possible that experiencing pain invalidation may also impact pain-reporting behavior in clinical settings. Across 2 separate samples of emerging adults, we examined whether exposure to invalidation of one's pain was associated with cognizant modulation of one's subjective acute pain ratings within routine medical and dental settings. Drawing upon social psychological theories of impression management and self-presentation, we hypothesized that exposure to pain invalidation would be associated with the under-rating of one's pain. In Study 1, previous experiences of invalidation were associated with under-rating of one's pain when visiting the doctor and the dentist. Study 2 found that invalidation from family and medical professionals-but not from friends-was associated with under-rating pain in both settings. Findings provide further evidence for the harmful effects of pain invalidation, particularly for emerging adults, as the dismissal of one's subjective experience may sow self-doubt while reinforcing cultural stigmas against pain, leading to alterations in pain communication that ultimately creates barriers to efficacious clinical treatment and care and increase pain-related suffering. PERSPECTIVE: Pain invalidation imparts harm to those who already suffer from pain, be it mentally, physically, and/or behaviorally. We show that people who have encountered invalidation are more likely to under-rate their pain when seeking care, impeding assessment and treatment, and further highlighting the importance of clinical validation of pain experiences., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

The study was conducted in a descriptive type to evaluate the pain behavior and hemodynamic parameters during aspiration of intubated and mildly sedatized patients in the intensive care unit. The study sample consisted of 100 intubated and sedatized patients who were hospitalized in the Anesthesia Intensive Care Unit of Harran University Faculty of Medicine Hospital between February 2018 and June 2018. "Patient Information Form", "Hemodynamic Parameter Form", "Behavioral Pain Scale (BPS)", "Ramsay Sedation Scale" and "Glasgow Coma Scale (GCS)" were used to collect the data. There is a significant difference between the BPS total and subscale scores, mean "systolic and diastolic blood pressure", "heart rate", "respiratory rate" and "SpO2 " before, during and after aspiration (p=0.0001), it was determined that the difference was due to the average score after aspiration (p=0.0001). While the SpO2 averages of intubated and sedatized intensive care patients decrease during aspiration, the averages of the BPS scores and other hemodynamic parameters increase. [ABSTRACT FROM AUTHOR]

Previous studies suggest that adenosine A1 receptors (A1R) modulate the processing of pain. The aim of this study was to characterize the distribution of A1R in nociceptive tissues and to evaluate whether targeting A1R with the partial agonist capadenoson may reduce neuropathic pain in mice. The cellular distribution of A1R in dorsal root ganglia (DRG) and the spinal cord was analyzed using fluorescent in situ hybridization. In behavioral experiments, neuropathic pain was induced by spared nerve injury or intraperitoneal injection of paclitaxel, and tactile hypersensitivities were determined using a dynamic plantar aesthesiometer. Whole-cell patch-clamp recordings were performed to assess electrophysiological properties of dissociated DRG neurons. We found A1R to be expressed in populations of DRG neurons and dorsal horn neurons involved in the processing of pain. However, administration of capadenoson at established in vivo doses (0.03–1.0 mg/kg) did not alter mechanical hypersensitivity in the spared nerve injury and paclitaxel models of neuropathic pain, whereas the standard analgesic pregabalin significantly inhibited the pain behavior. Moreover, capadenoson failed to affect potassium currents in DRG neurons, in contrast to a full A1R agonist. Despite expression of A1R in nociceptive neurons, our data do not support the hypothesis that pharmacological intervention with partial A1R agonists might be a valuable approach for the treatment of neuropathic pain. [ABSTRACT FROM AUTHOR]

This study aimed to determine the role of dexmedetomidine (Dex) in neuropathic pain (NP) after chronic constriction injury (CCI) in a rat model as well as its underlying mechanism. First, a CCI rat model was established. After treatment with Dex, the severity of NP was ascertained by monitoring paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) at different time points. Immunohistochemical analysis was performed to determine the levels of Keap1 and Nrf2 in the spinal cord. Furthermore, the levels of Keap1–Nrf2–HO-1 pathway molecules, apoptotic proteins, and antioxidant genes in the spinal cord or isolated primary microglia were determined using quantitative polymerase chain reaction and western blotting. The release of proinflammatory cytokines was detected via enzyme-linked immunosorbent assay. To evaluate Dex-treated CCI-induced NP via the Keap1–Nrf2–HO-1 pathway, the rats were intrathecally injected with lentivirus to upregulate or downregulate the expression of Keap1. We found that Dex inhibited pathological changes and alleviated sciatic nerve pain as well as repressed inflammation, apoptosis, and redox disorders of the spinal cord in CCI rats. Keap1 protein expression was substantially downregulated, whereas Nrf2 and HO-1 expressions were significantly upregulated in the spinal cord after Dex administration. Additionally, Keap1 overexpression counteracted Dex-mediated inhibition of NP. Keap1 overexpression led to a decrease in Nrf2 and HO-1 levels as well as PWT and PWL but led to an aggravation of inflammation and antioxidant disorders and increased apoptosis. Keap1 silencing alleviated NP in rats with CCI, as evidenced by an increase in PWT and PWL. Keap1 depletion resulted in the alleviation of inflammation and spinal cord tissue injury in CCI rats. Collectively, these findings suggest that Dex inhibits the Keap1–Nrf2–HO-1-related antioxidant response, inflammation, and apoptosis, thereby alleviating NP in CCI rats.

Chronic constriction injuries (CCI) of the sciatic nerve are widely used nerve entrapment animal models of neuropathic pain. Two common pain behaviors observed following CCI are thermal hyperalgesia and mechanical allodynia, measured by the Hargreaves and von Frey tests, respectively. While thermal hyperalgesia tends to recover by 30 days, mechanical allodynia can persist for many more months thereafter. Consequently, mechanical allodynia has been used extensively as a measure of ‘chronic pain’ focusing on the circuitry changes that occur within the spinal cord. Here, using the sciatic nerve cuff variant of CCI in mice, we propose that in contrast to these evoked measures of nociceptive hypersensitivity, dynamic weight bearing provides a more clinically relevant behavioral measure for ongoing pain during nerve injury. We found that the effect of sciatic nerve cuff on the ratio of weight bearing by the injured relative to uninjured hindlimbs more closely resembled that of thermal hyperalgesia, following a trend toward recovery by 30 days. We also found an increase in the percent of body weight bearing by the contralateral paw that is not seen in the previously tested behaviors. These results demonstrate that dynamic weight bearing is a reliable measure of non-evoked neuropathic pain and suggest that thermal hyperalgesia, rather than mechanical allodynia, provides a proxy measure for nerve entrapment-induced ongoing pain.

Objective: The purpose of the study was to compare the pain-related behavior and the pain perception associated with three anesthetic techniques in pulpotomies of primary mandibular second molars: traditional inferior alveolar nerve block (IANB), IANB with computer-controlled local anesthetic delivery (CCLAD), and intraligamental anesthesia with CCLAD. Method and Materials: The sample comprised 91 randomly selected healthy children aged 5 to 9 years, who were scheduled for pulpotomy in the mandibular second molar. Patients were divided into three groups according to the type of anesthesia received. Group A received traditional IANB, group B received IANB with CCLAD, and group C received intraligamental anesthesia with CCLAD. Pain-related behavior and pain perception levels were assessed using the established behavior code and the Wong-Baker FACES Pain Rating Scale respectively. Results: The mean of pain-related behavior was significantly lower (P< .001) in the intraligamental anesthesia with CCLAD group than in the other two groups. The pain perception scores were significantly higher in the traditional IANB group than in the IANB with CCLAD group, and the intraligamental anesthesia with CCLAD group (P = .044 and P <.001 respectively). The mean ± SD of the pain perception of IANB was 1.39 ± 0.200, IANB with CCLAD was 0.87 ± 0.133 and ILA with CCLAD was 0.13±0.063. Conclusion: Intraligamental anaesthesia with CCLAD was clearly associated with less pain than the IANB with or without CCLAD. [ABSTRACT FROM AUTHOR]

Background: Cognitive-affective factors influence the perception of pain and disability. These factors can lead to pain behaviors (PB) that can persist and become maladaptive. These maladaptive PB will further increase the risk of chronicity or persistence of symptoms and disability. Thus, clinicians must be prepared to recognize maladaptive PB in a clinical context. To date, in the context of assessment in a rehabilitation setting, PB in clinical settings are poorly documented. The main objective of this study was to identify direct observation methods and critically appraise them in order to propose recommendations for practice. As a secondary objective, we explored and extracted the different observable PB that patients could exhibit and that clinicians could observe. Methods: We conducted a comprehensive review on four databases with a generic search strategy in order to obtain the largest range of PB. For the first objective, a two-step critical appraisal used clinical criteria (from qualitative studies on barriers to implement routine measures) and psychometric criteria (from Brink and Louw critical appraisal tool) to determine which observation methods could be recommended for clinical practice. For the second objective, we extracted PB found in the literature to list potential PB that patients could exhibit, and clinicians could observe. Results: From the 3362 retrieved studies, 47 met the inclusion criteria for the first objective. The clinical criteria allowed us to select three observation methods. After the psychometric step, two observation methods were retained and recommended for clinical practice: the Behavioral Avoidance Test-Back Pain (BAT-Back) and the Pain Behaviour Scale (PaBS). For the second objective, 107 studies met the inclusion criteria. The extraction of the PB allowed us to list a large range of PB and classify the data in 7 categories of PB. Conclusion: Our results allowed us to recommend two observation methods for clinical practice. However, these methods have limitations and are validated only in chronic low back pain populations. With the extraction of PB presented in the literature, we contribute to better prepare clinicians to recognize PB in all patients who are experiencing pain. [ABSTRACT FROM AUTHOR]

Foot and mouth disease and lumpy skin disease of cattle is a common disease on commercial cattle farms which associated with changes in behavior, blood parameters, pain related behaviors and pain scale measurements, but little is known about this effect. The objectives of the present study were to test 2 hypotheses. First, investigate these changes; second, explained the effect of different treatment strategies (analgesic with Flunixin meglumine) or non-analgesic on lameness and pain scale. 125 bull cows were enrolled in the study based on visual observation of abnormal behavior the present study was done in Assiut governorate in Egypt was divided in three groups, which 25 clinically healthy bull (control group), FMD clinically infected group (25 analgesic + 25 non-analgesic and LSD (25 analgesic + 25 non analgesic). Obtained data illustrated that; there are significant increase physiological parameters (rectal temperature, heart rate and respiratory rate), lying behavior and total pain scale, while, there are significant decrease in feeding, drinking, rumination and standing behaviors, activity of exploration and activity of body care which may be corrected by Flunixin using. Conclusion: Flunixin injection may help in decreasing the negative pain behaviors and physiological changes caused by LSD or FMD

Abstract Animal models have provided a growing body of information about the pathophysiology of headaches and novel therapeutic targets. In recent years, experiments in awake animals have gained attention as more relevant headache models. Pain can be assessed in animals using behavioral alterations, which includes sensory-discriminative, affective-emotional and cognitive aspects. Spontaneous behavioral alterations such as increased grooming, freezing, eye blinking, wet dog shake and head shake and decreased locomotion, rearing, food or water consumption observed during pain episodes are oftentimes easy to translate into clinical outcomes, but are giving little information about the localization and modality of the pain. Evoked pain response such as tactile and thermal hypersensitivity measures are less translatable but gives more insight into mechanisms of action. Mechanical allodynia is usually assessed with von Frey monofilaments and dynamic aesthesiometer, and thermal allodynia can be evaluated with acetone evaporation test and Hargreaves’ test in animal models. Anxiety and depression are the most frequent comorbid diseases in headache disorders. Anxiety-like behaviors are evaluated with the open-field, elevated plus-maze or light/dark box tests. Interpretation of the latter test is challenging in migraine models, as presence of photophobia or photosensitivity can also be measured in light/dark boxes. Depressive behavior is assessed with the forced-swim or tail suspension tests. The majority of headache patients complain of cognitive symptoms and migraine is associated with poor cognitive performance in clinic-based studies. Cluster headache and tension type headache patients also exhibit a reversible cognitive dysfunction during the headache attacks. However, only a limited number of animal studies have investigated cognitive aspects of headache disorders, which remains a relatively unexplored aspect of these pathologies. Thus, the headache field has an excellent and growing selection of model systems that are likely to yield exciting advances in the future.

The aim of this work was to synthesize a diethyl phenylcarbamothioyl phosphonate (EThmP) and evaluate its biological activities. ThmP has been prepared with high yields and its conformation was determined. This phosphonothioamidate derivative was characterized by IR, and NMR Spectroscopy (1H, 13C, and 31P). On the component of EThmP, the Hirshfeld surface analysis indicates that the major contributions for the crystal packing are H···H (53.3%), H···O (12.9%) H···S (14.5%), and C···H (17.6%) interactions. An anti-nociceptive test (the formaline test) showed that the EThmP modulates the pain during the early and late phases proved by rat behavior characterized by absence of licking, biting and shaking of the affected paw. The modulation of pain by the EThmP may be due to its anti-inflammatory effect. The Hot Plate test showed that the pretreatment with the EThmP did not modulate the pain nociception induced by maintaining the rat at a fixed temperature of 48°C. The treated rats' behavior was characterized by elevating, licking the paw, jumping and fleeing. EThmP did not affect the memory capacity and acetylcholinesterase activity. The morbidity of rats was normal with no mortality or sign of toxicity. The in vitro study showed that the EThmP has no antibacterial, antifungal and antioxidant activities. The EThmP has an important dose dependent anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Transcutaneous electrical nerve stimulation (TENS) has been used to reduce pain or improve motor function in musculoskeletal and neurological disorders in the clinic. Although some studies have suggested electrotherapy as an intervention for edema, the effects and mechanisms of TENS on inflammation-induced edema remain unclear. Thus, we aimed to investigate the effects of TENS on arthritic pain with edema. 1% carrageenan was injected into the right tibiofemoral joint of 69 male Sprague-Dawley rats (200-250 g). After the development of arthritic pain, low-frequency (4-Hz, Low-TENS, n = 25) and high-frequency (100-Hz, High-TENS, n = 25) TENS with sub-motor threshold or placebo-TENS (n = 19) was applied for 20-min to medio-lateral part of the ipsilateral side. Weight bearing and knee-bend tests were used to assess pain-like behaviors. Also, we examined the size of edema and measured tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in the synovium by western blot. Eight rats in each of the two TENS groups were injected with Naloxone. Edema was reduced in the low- and high-frequency TENS groups at 6-h. TENS-treated rats showed reduced pain in the knee-bend test at 6-h. We observed decreased weight load shifts on the ipsilateral side in TENS groups. Naloxone reduced these effects. TNF-α and IL-1β expression decreased in the synovial membrane at 6-h. These results suggest that low- and high-frequency TENS have acutely positive effects on inflammatory edema, with the management of arthritic pain and reduction in pro-inflammatory mediators. Therefore, Low-TENS and High-TENS may be useful in treating acute inflammatory pain and edema.

PurposeCaregivers’ responses to pain behaviors of patients with chronic pain have an essential role in how patients perceive their pain condition. The current study investigated the mediating role of pain catastrophizing on the link between perceived caregiver responses and patient pain behaviors.Materials and MethodsThe sample of this cross-sectional study consisted of 200 patients with chronic pain (mean of age = 44.6; 71.5% were female). Participants responded to measures assessing their perception of their caregiver responses to their pain, their pain catastrophizing thoughts, and their pain behaviors.ResultsThe mediation analyses showed that perceived distracting responses were negatively related to pain catastrophizing level in patients, which in turn was positively associated with expressing pain behaviors. Besides, perceived caregiver negative responses were positively associated with catastrophizing thoughts, which in turn was positively related to expressing pain behaviors.ConclusionPatients’ perceptions regarding how their caregiver responds to their pain condition can be related to their thoughts about their pain and how they react to their pain situation. Investigating the external sources that might have an impact on patients’ reactions to their pain, especially when those external sources are caregivers who, in most situations, are with the patients for a prolonged duration, is essential.

Abstract Background For patients with advanced dementia, pain diagnosis and assessment requires observations of pain-indicative behavior by others. One type of behavior that has been shown to be a promising candidate is the facial response to pain. To further test how pain-indicative facial responses are, we investigated the predictive power of observational facial descriptors to (i) predict the self-report of pain and (ii) to differentiate between non-painful and painful conditions. In addition, the expertise of the observers (nurses vs. healthy controls) and the cognitive status of the observed (dementia vs. cognitively healthy) were considered. Methods Overall 62 participants (32 nurses and 30 control subjects) watched 40 video-clips, showing facial expressions of older individuals with and without dementia during non-painful and painful pressure stimulation. After each clip, participants were asked to rate the videos using commonly used facial descriptors of pain and also to provide global pain estimate ratings of how much pain the observed individual might have experienced. Results Out of the 12 facial descriptors used, only 7 were able to differentiate between non-painful and painful conditions. Moreover, participants were better in predicting the pain self-report of the observed individuals when using facial descriptors than when using global pain estimates. Especially, the anatomically-orienting descriptors (e.g. opened mouth, narrowing eyes) showed greatest predictive power. Results were not affected by pain-expertise of the observers (nurses vs. control subjects) or diagnostic status of the observed (patients with dementia vs. cognitively unimpaired subjects). Conclusions The fine-grained and specific observation of facial responses to acute pain appeared to provide valid indication of pain that is not compromised when patients with dementia are observed. The regular professional training does not put nurses at advantage to detect pain via facial responses.