Search

Palmitoylethanolamide (PEA) is emerging as a promising therapeutic agent for neuropathic and other pain-related conditions. This naturally occurring fatty acid has drawn interest because of its ability to regulate pain and inflammation. Initially identified in food sources, PEA has been the subject of extensive research to elucidate its properties, efficacy, and clinical applications. PEA primarily exerts its effects through interaction with its primary receptor PPAR α, this interaction influences pain signalling pathways and neuroinflammatory processes by modulating the synthesis of pro-inflammatory cytokines, mast cell degranulation, microglial activation, and decrease of oxidative stress. PEA's interaction with endocannabinoid receptors decreases the inflammatory cytokine and chemokine production and thereby a descending pain sensation. The pharmacological and pharmacokinetic characteristics of PEA are examined in this paper, along with its potential for efficiency when used in in combination additional therapies in a variety of neurodegenerative disease models, including multiple sclerosis, Parkinson's disease, and Alzheimer's. Experimental evidence shows that PEA not only reduces pain and inflammation but also lowers the need for higher dosages of other drugs hence minimizing the risk of drug toxicity. The bioavailability of PEA has been enhanced by recent technological developments, which emphasize continuous research efforts to maximize PEA's therapeutic potential in pain treatment and associated medical sectors. [ABSTRACT FROM AUTHOR]

Rationale: Opioid analgesics are the most effective medications used for the treatment of pain, however there are significant risks associated with repeated opioid use including opioid misuse and opioid use disorder development. Chronic pain affects millions of adults in the United States, and opioid misuse is often comorbid with pain conditions in individuals who are repeatedly treated with opioids. In addition to providing pain relief, opioids produce rewarding effects, but in chronic pain states, reward processing can become dysregulated. The conditioned place preference task is commonly used to measure the rewarding properties of opioids in rodents. During this task, opioid administration is paired with a distinct environment through repeated conditioning and the change in an animal's preference for the paired environment indicates whether the opioid is rewarding or not. Objectives: Rodent pain models can be combined with conditioned place preference to examine the effects of pain on opioid reward. The existing preclinical literature on pain effects on conditioned place preference is conflicting, where pain conditions have been reported to enhance, suppress, or have no effect on opioid reward. This review will discuss several factors that may contribute to these discordant findings including conditioning session duration and number, rodent strain differences in opioid sensitivity, analgesic properties of opioids at tested doses, locomotor effects at tested doses, and diurnal variation in pain sensitivity. Future studies should consider how these factors contribute to opioid conditioned place preference in both pain and pain-free animals to have a better understanding of the interactions between pain and opioid reward. [ABSTRACT FROM AUTHOR]

Objectives: We evaluate the presence of sensitization-associated symptoms and neuropathic pain features and identify if there is an association between these symptoms and pressure pain sensitivity, pain, and related-disability in lateral elbow tendinopathy. Methods: Thirty-seven (43% women, age: 45.5 ± 9.5 years) patients with lateral elbow tendinopathy completed: demographic (i.e. age, height, and weight); clinical (i.e. pain history, pain intensity, and Disabilities of the Arm, Shoulder and Hand); and psychophysical (i.e. pressure pain thresholds at the elbow, cervical spine, hand, and leg) outcomes, and the Central Sensitization Inventory and Self-administered Leeds Assessment of Neuropathic Symptoms and Signs questionnaires. Step-wise multiple linear regression models were performed to identify predictors of sensitization- or neuropathic-associated symptoms. Results: Six (16%) patients exhibited sensitization-associated symptoms (mean: 46.5, SD: 6.1), whereas 13 (35%) patients showed neuropathic-associated symptoms (mean: 13.5; SD: 1.4). Sensitization-associated symptoms were positively associated with neuropathic-associated symptoms (r = 0.538, P =.001) and negatively associated with pressure pain thresholds at the leg (r = -0.378, P =.021). Neuropathic-associated symptoms were positively associated with related-disability (r = 0.479, P =.003) and negatively associated with pressure pain threshold at the elbow (r = -0.394, P =.017). Stepwise regression analyses revealed that neuropathic-like symptoms explained 26.8% of the variance of sensitization symptoms (r2: 0.268), whereas pressure pain threshold at the elbow explained an additional 6.6% to neuropathic-like symptoms (r2: 0.334). Conclusion: This explorative study identified sensitization- and neuropathic-associated symptoms in 16% and 35% of the people with lateral elbow tendinopathy. Sensitization- and neuropathic-associated symptoms were associated. Pressure pain sensitivity at the elbow (peripheral sensitization) was associated with neuropathic -associated symptoms. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case describes a minimally invasive implantation of cryopreserved human adipose tissue allograft (CAT) in a diabetic neuropathic patient with a pre‐ulcerative plantar lesion. No re‐ulceration or adverse events have occurred out to 9 months. CAT provides healthcare providers with an option to manage patients at risk for plantar ulcers. [ABSTRACT FROM AUTHOR]

A 65-year-old female patient, with no known diseases and no regular medication usage, presented with a complaint of itching that had been ongoing for the past two years. Itching initially started in approximately five cm areas on the bilateral below-knee flexor surfaces. The patient, whose complaints persisted, was referred to the internal medicine outpatient clinic by dermatology. On physical examination, erythematous excoriated papules were observed in the areas affected by itching. The patient's blood sugar, liver and kidney function tests, complete blood count, erythrocyte sedimentation rate, thyroid function tests, urinalysis, stool parasitology were all normal or negative. The patient reported a sensation of coldness in the same area, was referred to neurosurgery to investigate the etiology of possible neuropathic itching. The patient's spinal imaging, revealed a spinal mass. She underwent surgery performed by a neurosurgeon, during which the spinal mass was completely removed. She reported that her itching had completely disappeared post-operatively. The concept of itching as a variant of pain is not very new. Any damage occurring in the central nervous system or peripheral nervous system that affects the neurons responsible for transmitting and processing itch can lead to neuropathic itching. Focusing on spinal cord pathologies, any condition that damages the spinal cord may cause itching, depending on the level of damage. In cases of itching with dermatomal localization, where pain, hot or cold sensations, and paroxysmal itching are present, additional imaging methods or investigations for etiology should be performed. [ABSTRACT FROM AUTHOR]

Post-traumatic trigeminal neuropathic pain is one of the rare complications that could follow orofacial procedures such as dental extraction. The incidence of this type of pain following craniofacial trauma ranges between 3% and 13% depending on the type of surgery. The inferior alveolar and lingual nerves are commonly affected following molar tooth extraction. Pain usually differs from one patient to another concerning intensity and distribution. Pulsed radiofrequency treatment is one of the most widely used techniques in chronic pain management. It focuses on generating heat using radiofrequency waves at higher voltages than conventional radiofrequency while keeping tissue temperature below the neuro-destructive range. This report aims to highlight the benefit of using trigeminal ganglion pulsed radiofrequency to manage neuropathic pain following molar extraction. [ABSTRACT FROM AUTHOR]

Postural orthostatic tachycardia syndrome (POTS) is a chronic illness with unknown mortality and high morbidity, often diagnosed in the adolescent years. Published literature regarding POTS primarily focuses on the adult population, and guidance on treatment in pediatrics is sparse. The purpose of this clinical review is to evaluate the current literature on the management of POTS in pediatric patients. A search was conducted using the Cochrane database, Google Scholar, and PubMed. Studies were included if they evaluated the management of POTS, primarily in pediatric patients. Case reports and series were excluded. Eight published studies met the inclusion and exclusion criteria. To date, there are no US Food and Drug Administration-approved agents for the treatment of POTS. However, select pharmacological therapies have shown positive outcomes by addressing symptom origins, such as providing heart rate control, peripheral autonomic modulation, and targeting hypovolemia. Targeted pharmacological therapies studied in children and young adults include ivabradine, metoprolol, midodrine, pyridostigmine, intravenous crystalloid fluids, and fludrocortisone. Before adding pharmacotherapeutic interventions, non-pharmacologic interventions such as patient education, avoidance of symptom-triggering environments and medications, dietary fluid and sodium supplementation, exercise, and use of compression garments should be first attempted. Although the body of evidence for the management of POTS is expanding, additional research is needed to determine safe and efficacious dosing and establish clear guidelines for POTS in the pediatric population. [ABSTRACT FROM AUTHOR]

This preface introduces the Journal of Neurochemistry Special Issue on pain research. While acute pain provides important sensory information, which aids in the protection of an organism, it can in some cases transition into a chronic state. Unfortunately, chronic pain is a highly disabling state characterised by intense and abnormal pain sensations, which are exacerbated by problematic psychosocial disturbances that are poorly treated by current drugs. This issue includes several reviews that address current issues spanning basic to clinical research on a range of pain syndromes. Also included is a collection of basic research articles investigating important aspects of pain signalling through to whole body aspects of pain integration. [ABSTRACT FROM AUTHOR]

Background: Pain management is a major unmet need in people with rheumatoid arthritis (RA). Although many patients are treated with disease modifying anti-rheumatic drugs (DMARDS), including biologic therapies, many people with RA continue to experience significant pain. We aimed to determine whether performing a comprehensive pain evaluation is feasible in people with active RA receiving conventional DMARDs and biologic therapies. Methods: The BIORA-PAIN feasibility study was an open-label, randomised trial, which recruited participants suitable for treatment with biologic therapy. The primary feasibility outcomes were recruitment, randomisation and retention of eligible participants. All participants underwent pain assessment for nociceptive, neuropathic and nociplastic pain during the 12-month study period, with quarterly assessments for VAS (Visual Analogue Scale) pain, painDETECT and QST (quantitative sensory testing). This trial was registered in clinicaltrials.gov NCT04255134. Results: During the study period, 93 participants were screened of whom 25 were eligible: 13 were randomised to adalimumab and 12 to abatacept. Participant recruitment was lower than expected due to the COVID-19 pandemic. Pain assessments were practical in the clinical trial setting. An improvement was observed for VAS pain from baseline over 12 months, with a mean (SEM) of 3.7 (0.82) in the abatacept group and 2.3 (1.1) in the adalimumab group. There was a reduction in painDETECT and improvement in QST measures in both treatment groups during the study. Participant feedback included that some of the questionnaire-based pain assessments were lengthy and overlapped in their content. Adverse events were similar in both groups. There was one death due to COVID-19. Conclusions: This first-ever feasibility study of a randomised controlled trial assessing distinct modalities of pain in RA met its progression criteria. This study demonstrates that it is feasible to recruit and assess participants with active RA for specific modalities of pain, including nociceptive, neuropathic and nociplastic elements. Our data suggests that it is possible to stratify people for RA based on pain features. The differences in pain outcomes between abatacept and adalimumab treated groups warrant further investigation. Trial registration: NCT04255134, Registered on Feb 5, 2020. [ABSTRACT FROM AUTHOR]

• Sex-specific neuroimmune patterns lead to identical repertoires of behaviour. • Following injury macrophage accumulation in the nerve was greater in females. • Following injury T-cell numbers in the nerve was larger in males. • Macrophages were observed only in the trigeminal ganglia of injured males. • T-cell numbers in trigeminal ganglia were similar in both males and females. Trigeminal neuropathic pain is emotionally distressing and disabling. It presents with allodynia, hyperalgesia and dysaesthesia. In preclinical models it has been assumed that cephalic nerve constriction injury shows identical molecular, cellular, and sex dependent neuroimmune changes as observed in extra-cephalic injury models. This study sought empirical evidence for such assumptions using the infraorbital nerve chronic constriction model (ION-CCI). We compared the behavioural consequences of nerve constriction with: (i) the temporal patterns of recruitment of macrophages and T-lymphocytes at the site of nerve injury and in the trigeminal ganglion; and (ii) the degree of demyelination and axonal reorganisation in the injured nerve. Our data demonstrated that simply testing for allodynia and hyperalgesia as is done in extra-cephalic neuropathic pain models does not provide access to the range of injury-specific nociceptive responses and behaviours reflective of the experience of trigeminal neuropathic pain. Similarly, trigeminal neuroimmune changes evoked by nerve injury are not the same as those identified in models of extra-cephalic neuropathy. Specifically, the timing, magnitude, and pattern of ION-CCI evoked macrophage and T-lymphocyte activity differs between the sexes. [ABSTRACT FROM AUTHOR]

Background: This exploratory study evaluated the presence of sensitization-associated and neuropathic-like symptoms and identified their association with pressure sensitivity, pain, and disability in patients with cervical dystonia (CD). Methods: Thirty-one patients with CD (74.2% women, age: 61.2 years, SD 10.1) participated. Data collected included clinical variables, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), the Central Sensitization Inventory (CSI), the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI), as well as widespread pressure pain thresholds (PPTs). Results: Patients with CD with pain (n = 20, 64.5%) showed higher scores on the TWSTRS disability subscale and the CSI (p < 0.001), and lower PPTs (p < 0.05). Fifteen patients (15/31, 48%) showed sensitization-associated symptoms (CSI ≥ 40), whereas five of the patients with pain (5/20, 25%) exhibited neuropathic-like symptoms (S-LANSS ≥ 12). The CSI and S-LANSS were positively associated with the TWSTRS, HADS-A and HADS-D, and negatively associated with PPTs. HADS-D and S-LANSS explained 72.5% of the variance of the CSI (r2: 0.725), whereas CSI explained 42.3% of the variance of the S-LANSS (r2: 0.423). Conclusions: Pain is an important source of disability in CD, and may be a consequence of different mechanisms, including sensitization. [ABSTRACT FROM AUTHOR]

Post-mastectomy pain syndrome (PMPS) is a type of chronic postsurgical pain that can be severe, debilitating and frequently encountered in clinical practice. Multiple studies have focused on prevention, identifying risk factors and treating this condition. Nonetheless, PMPS remains a complex condition to treat effectively. In this case report, we describe the use of percutaneous electrical nerve stimulation in a breast cancer patient who experienced PMPS refractory to conventional treatments. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a widespread clinical issue caused by somatosensory nervous system damage, affecting numerous individuals. It poses considerable economic and public health challenges, and managing it can be challenging due to unclear underlying mechanisms. Nevertheless, emerging evidence suggests that neurogenic inflammation and neuroinflammation play a role in developing pain patterns. Emerging evidence suggests that neurogenic inflammation and neuroinflammation play significant roles in developing neuropathic pain within the nervous system. Increased/decreased miRNA expression patterns could affect the progression of neuropathic and inflammatory pain by controlling nerve regeneration, neuroinflammation, and the expression of abnormal ion channels. However, our limited knowledge of miRNA targets hinders a complete grasp of miRNA's functions. Meanwhile, exploring exosomal miRNA, a recently uncovered role, has significantly advanced our comprehension of neuropathic pain's pathophysiology in recent times. In this review, we present a comprehensive overview of the latest miRNA studies and explore the possible ways miRNAs might play a role in the development of neuropathic pain. [ABSTRACT FROM AUTHOR]

Chronic pain resulting from peripheral nerve injury remains a common issue in the United States and affects 7 to 10% of the population. Regenerative Peripheral Nerve Interface (RPNI) surgery is an innovative surgical procedure designed to treat posttraumatic neuropathic pain, particularly when a symptomatic neuroma is present on clinical exam. RPNI surgery involves implantation of a transected peripheral nerve into an autologous free muscle graft to provide denervated targets to regenerating axons. RPNI surgery has been found in animal and human studies to be highly effective in addressing postamputation pain. While most studies have reported its uses in the amputation patient population for the treatment of neuroma and phantom limb pain, RPNI surgery has recently been used to address refractory headache, postmastectomy pain, and painful donor sites from the harvest of neurotized flaps. This review summarizes the current understanding of RPNI surgery for the treatment of chronic neuropathic pain. [ABSTRACT FROM AUTHOR]

N-arachidonoylethanolamine (also known as anandamide) and 2-arachidonoylglycerol are activators of the cannabinoid receptors. The endocannabinoid system also includes structurally and functionally related lipid mediators that do not target cannabinoid receptors, such as oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide. These bioactive lipids are involved in various physiological processes, including regulation of pain. The primary aim of the study was to analyze associations between serum levels of these lipids and pain in participants in the Pain in Neuropathy Study, an observational, cross-sectional, multicentre, research project in which diabetic patients with painless or painful neuropathy underwent deep phenotyping. Our hypothesis was that painful neuropathy would be associated with higher levels of the 5 lipids compared with painless neuropathy. Secondary aims were to analyze other patient-reported outcome measures and clinical data in relationship to lipid levels. The lipid mediators were analyzed in serum samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum levels of anandamide were significantly higher in the painful group, but the effect size was small (Cohen d = 0.31). Using cluster analysis of lipid data, patients were dichotomized into a “high-level” endocannabinoid group and a “low-level” group. In the high-level group, 61% of patients had painful neuropathy, compared with 45% in the low-level group (P = 0.039). This work is of a correlative nature only, and the relevance of these findings to the search for analgesics targeting the endocannabinoid system needs to be determined in future studies. [ABSTRACT FROM AUTHOR]

Neuropathic itch is a relatively common yet under-reported cause of systemic pruritus. It is a debilitating condition often associated with pain, which impairs the patient's quality of life. Although much literature exists about renal and hepatic pruritus, there is a dearth of information and awareness about neuropathic itch. The pathogenesis of neuropathic itch is complex and can result from an insult at any point along the itch pathway, ranging from the peripheral receptors and nerves until the brain. There are several causes of neuropathic itch, many of which do not produce any skin lesions and are thus, often missed. A detailed history and clinical examination are necessary for the diagnosis, while laboratory and radiologic investigations may be needed in select cases. Several therapeutic strategies currently exist involving both non-pharmacological and pharmacological measures, the latter including topical, systemic, and invasive options. Further research is ongoing to clarify its pathogenesis and to design newer targeted therapies with minimal adverse effects. This narrative review highlights the current understanding of this condition, focusing on its causes, pathogenesis, diagnosis, and management, along with newer investigational drugs. [ABSTRACT FROM AUTHOR]

The article explores the relationship between senile gluteal dermatosis (SGD) and lumbosacral spine abnormalities in patients who do not fit the typical clinical profile of SGD. Through a retrospective case series, it was found that overweight patients with skin hyperkeratosis or ulceration, lower back pain, and unresponsive skin lesions had varying degrees of lumbosacral spinal involvement. The study suggests that lumbosacral neuropathic compromise could be a contributing mechanism for SGD alongside diabetes mellitus, highlighting the need for further research to understand this potential association. The findings indicate that investigating underlying lumbar compromise may be beneficial for patients with atypical SGD and lower back pain. [Extracted from the article]

We report a case of a 47-year-old male who presented with altered mental status. A review of his records revealed a weight loss of 20 lbs over the past 6 years, a recent hospitalization for idiopathic polyneuropathy with failure to thrive, and prior surgeries for peptic ulcer disease and small bowel obstruction. He was alert but had retrograde amnesia and peripheral neuropathy. A diagnosis was made, and the patient improved with treatment but was unfortunately left with irreversible neurological deficits. We discuss the importance of recognizing the extraintestinal manifestations of gastrointestinal dysfunction following gastrointestinal surgery. [ABSTRACT FROM AUTHOR]

Caudal epidural block is a simple and safe technique with a low complication rate commonly used for pediatric anesthesia and treatment of chronic lumbosacral pain. However, it is not exempt from some risks that, although infrequent, should be known. We describe the case of a 48-year-old female with chronic lumbosacral radicular pain who underwent caudal epidural infiltration. During the withdrawal of the catheter, accidental breakage and retention of a fragment at the level of the anterior epidural space of the sacrum occurred. We choose to have an expectant management with regular controls and a radiological lumbosacral computed tomography (CT) scan. Since the catheter was placed under sterile conditions, no prophylactic antibiotic treatment was considered. The patient showed no adverse events during the 6 months following catheter rupture. To our knowledge, there are no reports of epidural catheter breakage at the caudal level in adults. This is why there is no standardized protocol on how to proceed in these cases, and the handling of this situation must be individualized. [ABSTRACT FROM AUTHOR]

Diabetic foot complications represent a substantial health burden and are the foremost cause of hospitalization in patients with diabetes. Diabetes mellitus (DM) is known to cause several other problems. Diabetes is rapidly becoming the leading cause of illness and death worldwide. Diabetic foot ulcers (DFU) are one of the most painful complications of diabetes. These complications cause problems in blood vessels, nerves, and other organs throughout the body. DFU pathophysiology is attributed to a triad of neuropathies, trauma with secondary infection, and arterial occlusive disease. This review aims to identify the types of wounds that diabetics can develop. Owing to the complexity of their disease pathology, diabetics are susceptible to a variety of wounds, such as diabetic ulcers due to trauma (DUDT); neuropathic, ischemic, neuroischemic, arterial, venous, and mixed wounds; and diabetic bullae, furuncles, cellulitis, and carbuncles. Therefore, it is essential for healthcare providers to recognize the specific classification of a diabetic wound based on its distinctive attributes to provide appropriate wound care and therapeutic interventions. In the context of individuals with diabetes, it is of paramount significance to precisely identify the types of wounds during the initial evaluation to provide appropriate care and treatment, thereby enhancing the probability of favorable outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Low back pain is one of the most common presenting symptom among patients seeking medical help, accounting for approximately 85% of the cases. It affects individuals of all age groups and genders. Predominantly back pain is non specific, lacking identifiable patho-anatomy, while a lesser-known type, specific low back pain, demonstrates identifiable aetiology and pathology. This poses a challenge for physicians, as they must not only determine the underlying cause but also formulate categorical treatments for Chronic Low Back Pain (CLBP). Aim: To assess the prevalence of different types of CLBP based on clinical examination, past history, age, and gender in the overall population of the study. Materials and Methods: A cross-sectional study was conducted at Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar, Odisha, India, from August 2019 to July 2021. A total of 1,640 patients were examined in the orthopedics outpatient department, of which 1,000 patients aged between 20 and 60 years, with back pain lasting three months, were included in the study. All patients underwent a detailed clinical evaluation, including history and physical examination. The final type of CLBP was determined based on the predominant symptom. Data analysis was performed using Microsoft Excel software. Results: The male-to-female ratio was 1.23:1, and the average age was 43.1 years. The most common type of CLBP was neuropathic (n=473, 47.3%), followed by discogenic CLBP (n=255, 25.5%). The least common type was coccydynia (n=4, 0.4%). Facetogenic CLBP had the highest average age of presentation (57.3 years), while postural CLBP had the lowest average age (29.6 years). Conclusion: Neuropathic CLBP was the most common type, followed by discogenic CLBP, with sacroiliitis and coccydynia being less common. Detailed clinical evaluation aids in classifying different types of CLBP, which can help avoid unnecessary investigations, except for the neuropathic type and, to some extent, instability CLBP. [ABSTRACT FROM AUTHOR]

Background: A mechanism-based approach to the evaluation and management of pain has been suggested across disciplines in contemporary research. However, the translation of pain mechanism assessment strategies in research to clinical practice is unclear. This study sought to explore perceptions and use of clinical pain mechanism assessment by physical therapists managing musculoskeletal pain. Methods: This was an electronic cross-sectional survey. After initial development, refinement, and piloting for comprehensiveness, comprehensibility and relevance, the survey was disseminated to members of the Academy of Orthopaedic Physical Therapy via email listserv. Data was maintained anonymously using the online database REDCap. Descriptive statistics and Spearman's correlations for non-parametric data were analyzed for frequencies and associations across variables. Results: In total, 148 respondents completed all aspects of the survey. Respondent age ranged from 26 to 73 years, with a mean (SD) of 43.9 (12.0). Most respondents (70.8%) reported performing clinical pain mechanism assessments at least 'sometimes'. A majority (80.4%) believed clinical pain mechanism assessments are useful in guiding management strategies while 79.8% reported specifically choosing interventions to alter aberrant pain mechanisms. The most commonly used pain severity, physical examination testing and questionnaires were the numeric pain rating scale, pressure pain thresholds and pain diagrams, respectively. However, the vast majority of instruments to clinically assess pain mechanisms were performed by a small proportion of respondents (< 30%). There were no significant correlations between age, years of experience, highest earned degree, completion of advanced training or specialist certification and testing frequency. Conclusion: The evaluation of pain mechanisms involved in the pain experience is becoming common in research. The clinical application of pain mechanism assessment is unclear. Based on the results of this survey, physical therapists in the orthopedic setting believe pain mechanism assessment is useful, but data suggests it is infrequently performed. Additional research to uncover clinician motivation related to pain mechanism assessment is warranted. [ABSTRACT FROM AUTHOR]

Background: Rotator cuff‐related shoulder pain (RCRSP) was proposed to have a complex pain mechanism, but the exact aetiology is still unclear. A recent review summarised the updated research to analyse the traditional concept of shoulder impingement which may not be accurate. Current studies have demonstrated that mechanical factors including a reduction in subacromial space, scapular dyskinesia and different acromial shapes are unlikely directly contributing to RCRSP. Aims: Since the precise RCRSP pain mechanism remains unclear, the aim of this narrative review is to discuss possible sources of pain contributing to RCRSP according to the mechanisms‐based pain classifications. Results and Discussion: Research findings on potential mechanical nociceptive factors of RCRSP are conflicting; investigations of neuropathic and central pain mechanisms of RCRSP are limited and inconclusive. Overall, available evidence has indicated moderate to strong correlations between RCRSP and chemical nociceptive sources of pain. Conclusion: Results from current research may provide new directions for future studies on the aetiology of RCRSP and its clinical management towards a biochemical view instead of the traditional mechanical hypothesis. [ABSTRACT FROM AUTHOR]

Background: Like the increased clinical use of gabapentin, these trends appear to chronologically align with the opioid overdose crisis and particularly with the increased restrictions on opioid prescription. Among the published literature, the prevalence of gabapentin misuse has been estimated at 1.6% to 6.6% in the general population and 3% to 68% among individuals with a substance use disorder. Gabapentin is well tolerated when consumed at or below the FDA maximum recommended dose of 3600 mg/day. Objective: the study aims to assess and compare between clinical variables, rate of relapses, Overdose symptoms, pain quality and severity, among patients with OUD only and Opioid with comorbid GUD. Furthermore, this study was conducted to assess clinical correlates in relation to socio-demographics, personality disorders and degree of addiction severity in patient with OUD only and Opioid with comorbid GUD. Patients and Methods: The study was carried out at Okasha Institute of Psychiatry, Ain Shams University, particularly the outpatient clinic and inpatient unit of addiction medicine. Participants were selected as sample sizes of 30 and 30 according to those meeting, the inclusion Criteria for participants: diagnosed with opioid use disorder/opioid use disorder with comorbid gabapentin use disorder according to DSM-V, both genders, aged between (18 - 45) years old, Egyptian nationality, and Agreement for written informed consent for participation in this study. Results: In our study, dose of oral opioid was found to be more than 225mg in 46.7% of the opioid group and less than 225mg in 33.3% of the gabapentin group with an evident statistically high significant difference between both groups and a P-value of 0.004, while heroin sniffing was 76.7% in the opioid group and 33.3% in the gabapentin group with an evident statistically high significant difference between both groups and a P-value of 0.001 and regarding dose of sniffed heroin, it was >1gm in 70% of the opioid group and in 10% of the gabapentin group with an evident statistically high significant difference between both groups and a P-value of 0.000. In addition, heroin IV route was 70% in the opioid group and 20% in the gabapentin group with an evident statistically high significant difference between both groups and a P-value of 0.000 and regarding dose of IV heroin, it was >1gm in 63.3% of the opioid group and in 13.3% of the gabapentin group with an evident statistically high significant difference between both groups and a P-value of 0.000. Euphoria was found to be the desirable effect in 86.7% of the opioid group and 23% of the gabapentin group, meanwhile, pain relief was the desirable effect in 3.3% in the opioid group and 66.2%in the Gabapentin group with an evident statistically high significant difference between both groups and a P-value of 0.000. Regarding overdose, it was found to be 16.7% of the opioid group and 56.7%% of the Gabapentin group with statistical significance between both groups and a P-value of 0.018. Respiratory complications were found to be 20% of Gabapentin group statistical significance between both groups and a P-value of 0.049. Moreover, regarding history of pain, the percentage was 16.7% in the opioid group and 83.3% % in the gabapentin group with high significance between both groups and a P-value of 0.000. Also, the presence of significant neuropathic pain was 3.3% in the opiod group versus 80% in the Gabapentin group. There was a high significance between both groups with a P-value of 0.000. Regarding addiction severity, the percentage of very severe medical problems was 36.7%% in the opioid group and 13.3% % in the gabapentin group with high significance between both groups and a P-value of 0.025, inaddition, the percentage of mild psychiatric problems was 23.3%% in the opioid group and 10% % in the gabapentin group with high significance between both groups and a P-value of 0.023. Finally, the current study showed that the incidence of abstinence was 83.3% in the opioid group and 56.7% in the gabapentin group with statistical significance between both groups and a P-value of 0.024. Conclusion: The current study showed that patients with opioid with comorbid GUD were associated with higher incidence overdose, history of pain and presence of significant neuropathic pain. The incidence of pain relief as a desirable effect higher in patients with opioid with comorbid GUD compared to patients with OUD. While, the incidence of euphoria as a desirable effect was higher in patients with OUD compared to patients with opioid with comorbid GUD. The patients with OUD have higher incidence of abstinence compared to patients with opioid with comorbid GUD. The patients with OUD have higher doses of oral, Sniffed, and IV opioids compared to patients with opioid with comorbid GUD. OUD patients have more severe medical and psychiatric problems than with comorbid GUD. [ABSTRACT FROM AUTHOR]

To give an overview of central aspects of pain medicine-specific clinical reasoning when assessing a pain patient. Clinical reasoning is the thinking and decision-making processes associated with clinical practice. Three core pain assessment areas that are crucial for clinical reasoning in the field of pain medicine are discussed, each of them consisting of three points. First, it is important to distinguish acute, chronic non-cancer, and cancer-related pain conditions. This classical and very simple trichotomy still has important implications treatment-wise, e.g., concerning the use of opioids. Second, the pain mechanism needs to be assessed. Is the pain nociceptive, neuropathic, or nociplastic? Simply put, nociceptive pain has to do with injury of non-neural tissue, neuropathic pain is caused by a disease or lesion of the somatosensory nervous system, and nociplastic pain is believed to be related to a sensitized nervous system (c.f. the concept of "central sensitization"). This also has implications concerning treatment. Some chronic pain conditions are nowadays viewed more as diseases rather than the pain being merely a symptom. In the new ICD-11 pain classification, this is conceptualized by the characterization of some chronic pains as "primary". Third, in addition to a conventional biomedical evaluation, psychosocial and behavioral aspects must also be assessed, the pain patient being viewed as an active agent and not merely as the passive recipient of an intervention. Hence, the importance of a dynamic bio-psycho-social perspective. The dynamic interplay of biological, psychological, and social aspects must be taken into account, putative behavioral "vicious circles" thereby being identified. Some core psycho-social concepts in pain medicine are mentioned. The clinical applicability and clinical reasoning power of the 3 × 3 framework is illustrated by three short (albeit fictional) case descriptions. [ABSTRACT FROM AUTHOR]

Chemotherapy‐induced peripheral neuropathy (CIPN) is a major side effect of several anticancer agents including paclitaxel, a chemotherapeutic drug widely used in cancer treatment. CIPN deteriorates patients' quality of life and compromises cancer treatment. Dysfunction or injury of mitochondria has been suggested to be involved in the induction of this neuropathy. SS‐20 is a tetrapeptide that targets mitochondria and restores mitochondrial bioenergetics. This study was aimed to examine the protective effect of SS‐20 against paclitaxel‐induced peripheral neuropathy using a murine model. Repeated administration of paclitaxel to mice induced peripheral neuropathy as demonstrated by the presence of mechanical allodynia and the loss of intraepidermal nerve fibers in the hind paw. Concomitant administration of SS‐20 protected against the development of the neuropathy. Our results suggest that SS‐20 may be a drug candidate for the prevention of CIPN. [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]

Background: Both pain catastrophizing and neuropathic pain have been suggested as prospective risk factors for poor postoperative pain outcomes in total joint arthroplasty (TJA). Objective: We hypothesized that pain catastrophizers, as well as patients with pain characterized as neuropathic, would exhibit higher pain scores, higher early complication rates and longer lengths of stay following primary TJA. Methods: A prospective, observational study in a single academic institution included 100 patients with end-stage hip or knee osteoarthritis scheduled for TJA. In pre-surgery, measures of health status, socio-demographics, opioid use, neuropathic pain (PainDETECT), pain catastrophizing (PCS), pain at rest and pain during activity (WOMAC pain items) were collected. The primary outcome measure was the length of stay (LOS) and secondary measures were the discharge destinations, early postoperative complications, readmissions, visual analog scale (VAS) levels and distances walked during the hospital stay. Results: The prevalence of pain catastrophizing (PCS ≥ 30) and neuropathic pain (PainDETECT ≥ 19) was 45% and 20.4%, respectively. Preoperative PCS correlated positively with PainDETECT (rs = 0.501, p = 0.001). The WOMAC positively correlated more strongly with PCS (rs = 0.512 p = 0.01) than with PainDETECT (rs = 0.329 p = 0.038). Neither PCS nor PainDETECT correlated with the LOS. Using multivariate regression analysis, a history of chronic pain medication use was found to predict early postoperative complications (OR 38.1, p = 0.47, CI 1.047–1386.1). There were no differences in the remaining secondary outcomes. Conclusions: Both PCS and PainDETECT were found to be poor predictors of postoperative pain, LOS and other immediate postoperative outcomes following TJA. [ABSTRACT FROM AUTHOR]

Background and Objective: Neuropathic diseases are neurodegenerative conditions and a wide and difficult group of peripheral nerve diseases in humans. Since well-being therapy emphasizes the high levels of six domains of psychological well-being, this study was conducted to investigate the effectiveness of well-being therapy on pain coping strategies and self-efficacy of patients with chronic neuropathic pain. Methods: This clinical trial was conducted on 30 chronic neuropathic patients referred to Ayatollah Rouhani hospital in Babol and a neurologist's private office in two groups of experimental and control (n=15). Well-being therapy was performed in 8 sessions of 120 minutes, once a week for the experimental group, while the control group received the routine treatment. After the follow-up period, the control group also underwent psychotherapy. Both groups completed questionnaires of pain coping strategies (Rosenstiel and Keefe, 1985) and pain self-efficacy (Nicholas, 1989) in the pre-test, post-test and follow-up (two months after the post-test) and were compared. Findings: The results showed that there was a statistically significant difference between the two experimental and control groups in the score of the subscales of pain coping strategies in distraction from pain (23.13±3.88 versus 11.47±7.34) (p<0.001), reinterpretation of pain (17.33±5.56 versus 13.0±8.65) (p=0.114), catastrophizing (10.0±6.24 versus 16.33±5.4) (p<0.001), ignoring pain (24.4±6.67 versus 12.6±5.11) (p<0.001), hoping/praying (29.13±9.97 versus 22.4±5.7) (p=0.031), self-talk (25±4.03 versus 21.2±4.79) (p=0.026), behavioral activation (20.47±4.43 versus 11.20±4.94) (p<0.001) and pain self-efficacy (43.2±9.45 versus 33.33±13.34) (p=0.027). These results were maintained in the follow-up period. Conclusion: The present study showed that wellness therapy can be an effective intervention in improving pain coping strategies and increasing pain self-efficacy in chronic neuropathic patients. [ABSTRACT FROM AUTHOR]

A correct anamnesis and physical examination are basic to carry out an adequate diagnostic orientation and therapeutic plan for any type of pain. This will allow us to define its characteristics well in order to carry out a good differential diagnosis. We present the case of a patient referred from Neurology department due to chronic pain in the left thigh, initially classified as neuropathic pain. After evaluation and follow-up in our unit, he was finally diagnosed with cancer pain secondary to a metastatic lesion. It is extremely important to reassess any patient referred to the pain unit, paying attention to any warning signs. This may serve as a guide for the diagnosis of other diseases such as malignant neoplasms, whose prognosis will be influenced by early treatment. [ABSTRACT FROM AUTHOR]

Ambroxol is a multifaceted drug with primarily mucoactive and secretolytic actions, along with anti-inflammatory, antioxidant, and local anaesthetic properties. It has a long history of use in the treatment of respiratory tract diseases and has shown to be efficacious in relieving sore throat. In more recent years, ambroxol has gained interest for its potential usefulness in treating neuropathic pain. Research into this area has been slow, despite clear preclinical evidence to support its primary analgesic mechanism of action—blockade of voltage-gated sodium (Nav) channels in sensory neurons. Ambroxol is a commercially available inhibitor of Nav1.8, a crucial player in the pathophysiology of neuropathic pain, and Nav1.7, a particularly exciting target for the treatment of chronic pain. In this review, we discuss the analgesic mechanisms of action of ambroxol, as well as proposed synergistic properties, followed by the preclinical and clinical results of its use in the treatment of persistent pain and neuropathic pain symptoms, including trigeminal neuralgia, fibromyalgia, and complex regional pain syndrome. With its well-established safety profile, extensive preclinical and clinical drug data, and early evidence of clinical effectiveness, ambroxol is an old drug worthy of further investigation for repurposing. As a patent-expired drug, a push is needed to progress the drug to clinical trials for neuropathic pain. We encourage the pharmaceutical industry to look at patented drug formulations and take an active role in bringing an optimized version for neuropathic pain to market. [ABSTRACT FROM AUTHOR]

Diabetic foot complications represent a substantial health burden and are the foremost cause of hospitalization in patients with diabetes. Diabetes mellitus (DM) is known to cause several other problems. Diabetes is rapidly becoming the leading cause of illness and death worldwide. Diabetic foot ulcers (DFU) are one of the most painful complications of diabetes. These complications cause problems in blood vessels, nerves, and other organs throughout the body. DFU pathophysiology is attributed to a triad of neuropathies, trauma with secondary infection, and arterial occlusive disease. This review aims to identify the types of wounds that diabetics can develop. Owing to the complexity of their disease pathology, diabetics are susceptible to a variety of wounds, such as diabetic ulcers due to trauma (DUDT); neuropathic, ischemic, neuroischemic, arterial, venous, and mixed wounds; and diabetic bullae, furuncles, cellulitis, and carbuncles. Therefore, it is essential for healthcare providers to recognize the specific classification of a diabetic wound based on its distinctive attributes to provide appropriate wound care and therapeutic interventions. In the context of individuals with diabetes, it is of paramount significance to precisely identify the types of wounds during the initial evaluation to provide appropriate care and treatment, thereby enhancing the probability of favorable outcomes. [ABSTRACT FROM AUTHOR]

Background: Chronic pain is a common non-motor symptom in patients with Parkinson's disease (PD). Aim: To facilitate the diagnosis of pain in PD, we developed a new classification system the Parkinson's disease pain classification system (PD-PCS) and translated the corresponding validated questionnaire into German. Methods: A causal relationship of the respective pain syndrome with PD can be determined by four questions before assigning it hierarchically into one of three pain categories (neuropathic, nociceptive and nociplastic). Results: In the initial validation study 77% of the patients (122/159) had PD-associated pain comprising 87 (55%) with nociceptive, 36 (22%) with nociplastic and 24 (16%) with neuropathic pain. The study revealed a high validity of the questionnaire and a moderate intrarater and interrater reliability. The questionnaire has been adapted into German and employed in 30 patients. Discussion: The PD-PCS questionnaire is a valid and reliable tool to determine the relationship of a pain syndrome with PD before classifying it according to the underlying category, facilitating further diagnostics and treatment. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate the changes in urodynamics and voiding cystourethrogram parameters on pre‐ and post‐untethering surgery in patients aged under 2 years with filum lipoma. Methods: Sixty‐two patients were enrolled in this study. The changes in urodynamics and voiding cystourethrogram parameters were compared before untethering surgery and 6 months after untethering surgery. These parameters were bladder volume, bladder deformity, vesicoureteral reflux during voiding cystourethrogram, detrusor overactivity, bladder compliance, and post‐void residual volume in urodynamics. Results: Bladder volume during voiding cystourethrogram and bladder compliance increased significantly from 89.8 ± 49.5 mL to 114.5 ± 50.5 mL (P = 0.0069) and 10.2 ± 6.2 mL/mmH2O to 17.0 ± 13.3 mL/mmH2O (P = 0.0008), respectively, at 6‐month follow‐up. Six patients required combination management with clean intermittent catheterization at 25.1 ± 8.2 months (14.3 ± 6.5‐months follow‐up) because of elevated post‐void residual volumes. Conclusions: According to voiding cystourethrogram results, bladder function and urodynamics in patients with filum lipoma significantly improved after untethering surgery. Non‐invasive assessment based on measurements of post‐void residual should be considered as a postoperative follow‐up method. [ABSTRACT FROM AUTHOR]

Physiological changes that occur during ageing can affect the incidence, experience and treatment of pain in older adults. This article reviews these physiological changes and how they can affect the best approach to management. [ABSTRACT FROM AUTHOR]

This study aimed to analyze correlations between Self-Report Leeds Assessment of Neuropathic Symptoms (S-LANSS) and PainDETECT with proxies of sensitization, pain-related, or psychological/cognitive variables in coronavirus disease, 2019 (COVID-19) survivors exhibiting post-COVID pain. Demographic, clinical, psychological, cognitive, sensitization-associated symptoms, and health-related quality of life were collected in 146 survivors with post-COVID pain. The PainDETECT and S-LANSS questionnaires were used for assessing neuropathic pain-related symptoms. Patients were assessed with a mean of 18.8 (SD 1.8) months after hospitalization. Both questionnaires were positively associated with pain intensity (p < 0.05), anxiety (PainDETECT p < 0.05; S-LANSS p < 0.01), sensitization-associated symptoms (p < 0.01), catastrophism (p < 0.01), and kinesiophobia (p < 0.01) and negatively associated with quality of life (PainDETECT p < 0.05; S-LANSS p < 0.01). Depressive levels were associated with S-LANSS (p < 0.05) but not with PainDETECT. The stepwise regression analyses revealed that 47.2% of S-LANSS was explained by PainDETECT (44.6%), post-COVID pain symptoms duration (1.7%), and weight (1.1%), whereas 51.2% of PainDETECT was explained by S-LANSS (44.6%), sensitization-associated symptoms (5.4%), and anxiety levels (1.2%). A good convergent association between S-LANSS and PainDETECT was found. Additionally, S-LANSS was associated with symptom duration and weight whereas PainDETECT was associated with sensitization-associated symptoms and anxiety levels, suggesting that the two questionnaires evaluate different aspects of the neuropathic pain spectrum in post-COVID pain patients. [ABSTRACT FROM AUTHOR]

This study aimed to describe a network including demographic, sensory-related, psychological/cognitive and other variables in individuals with post-COVID pain after hospitalization. Demographic (i.e., age, height, weight, months with symptoms), sensory-related (Central Sensitization Inventory -CSI-, Self-Report Leeds Assessment of Neuropathic Symptoms -S-LANSS-, PainDETECT), psychological/cognitive (Hospital Anxiety and Depression Scale -HADS-A/HADS-D-, Pain Catastrophizing Scale -PCS-, Tampa Scale for Kinesiophobia -TSK-11-) and other (sleep quality and health-related quality of life -EQ/5D/5L) variables were collected in 146 COVID-19 survivors with post-COVID pain. A network analysis was conducted to quantify the adjusted correlations between the modelled variables, and to assess their centrality indices (i.e., the connectivity with other symptoms in the network and the importance in the system modelled as network). The network revealed associations between sensory-related and psychological/cognitive variables. PainDETECT was associated with S-LANSS (ρ : 0.388) and CSI (ρ : 0.207). Further, CSI was associated with HADS-A (ρ : 0.269), TSK-11 (ρ : 0.165) and female gender (ρ : 0.413). As expected, HADS-A was associated with HADS-D (ρ : 0.598) and TSK-11 with PCS (ρ : 0.405). The only negative association was between sleep quality and EQ-5D-5L (ρ : −0.162). Gender was the node showing the highest strength, closeness, and betweenness centralities. In addition, CSI was the node with the second highest closeness and betweenness centralities, whereas HADS-D was the node with the second highest strength centrality. This is the first study applying a network analysis for phenotyping post-COVID pain. Our findings support a model where sensitization-associated symptoms, neuropathic phenotype, and psychological aspects are connected, reflecting post-COVID pain as a nociplastic pain condition. In addition, post-COVID pain is gender dependent since female sex plays a relevant role. Clinical implications of current findings, e.g., developing treatments targeting these mechanisms, are discussed. [ABSTRACT FROM AUTHOR]

Orofacial pain is one of the most widespread and debilitating diseases condition affecting the head, face, and temporomandibular joint (TMJ), as well as other tissues. It can arise from different aetiologies and occur in different regions. In contrast to neurovascular disorders like primary headache, which can manifest as persistent orofacial pain, trigeminal neuropathic problems are caused by damage from dental treatments, infections, neoplasms, or malfunction of the Peripheral or central nervous system. The sufferers' quality of life is impacted by all these trigeminal system disorders. When choosing a treatment plan for orofacial pain problems, a multidisciplinary strategy that uses both non-pharmacological and pharmacological way should be considered. [ABSTRACT FROM AUTHOR]

Background: Trigeminal‐mediated headshaking (TMHS) in horses is a form of neuropathic pain of undetermined cause that often results in euthanasia. The role of microbiota in TMHS has not been investigated in diseased horses. Objective: To investigate if gastrointestinal microbiota in the cecum is different in horses with TMHS compared to a control population, during a summer season with clinical manifestations of disease. Animals: Ten castrated horses: five with TMHS and five neurologically normal controls. Methods: All horses were sourced from our institution and kept under the same husbandry and dietary conditions. All horses were fed orchard grass hay for 30 days and then were euthanized due to chronic untreatable conditions including TMHS and orthopedic disease (control group). Caecal samples for microbiota analysis were collected within 20 min after euthanasia. Sequencing was performed using an Illumina MiSeq platform and the microbiome was analyzed. Results: The caecal microbiota of horses with TMHS was similar to control horses in terms of diversity but differed significantly with Methanocorpusculum spp. having higher abundance in horses with TMHS. Conclusions and clinical importance: Methanocorpusculum spp. was more abundant in the cecum of horses with TMHS. However, its role in disease is unknown. Furthermore, it could also represent an incidental finding due to our small population size. [ABSTRACT FROM AUTHOR]

Abstract: One in 5 patients with diabetes suffers from chronic pain with neuropathic characteristics, but the pathophysiological mechanisms underlying the development of neuropathic pain in patients with diabetic distal symmetrical polyneuropathy (DSP) are poorly understood. Systemic low-grade inflammation has been implicated, but there is still a considerable knowledge gap concerning its scope and meaning in this context. The aim of the study was to establish the broad inflammatory signature of painful diabetic DSP in serum samples from the Pain in Neuropathy Study, an observational cross-sectional multicentre study in which participants underwent deep phenotyping. In the present two cohorts exploration-replication study (180 participants in each cohort), serum samples from Pain in Neuropathy Study participants were analyzed with the Olink INFLAMMATION panel (Olink Bioscience, Uppsala, Sweden) that enables the simultaneous measurement of 92 inflammation-related proteins (mainly cytokines, chemokines, and growth factors). In both the exploration and the replication cohort, we identified a high-inflammation subgroup where 14 inflammation-related proteins in particular were associated with more neuropathy and higher pain intensity. The top 3 proteins were hepatocyte growth factor, colony-stimulating factor 1, and CD40 in both cohorts. In the exploratory cohort, additional clinical data were available, showing an association of inflammation with insomnia and self-reported psychological distress. Hence, this cross-sectional exploration-replication study seems to confirm that low-grade systemic inflammation is related to the severity of neuropathy and neuropathic pain in a subgroup of patients with diabetic DSP. The pathophysiological relevance of these proteins for the development of neuropathic pain in patients with diabetic DSP must be explored in more depth in future studies. [ABSTRACT FROM AUTHOR]

Pain is a common and highly distressing symptom in children with advanced malignancies and it is often multifactorial at the end-of-life. The prognosis of cancer pain is reported to be worse in those with mixed pain type, high pain severity, daily opioid use, and poor emotional well-being. We describe a case of 13-year-old boy, known case of metastatic Ewing sarcoma right iliac bone, who presented to our palliative care ward with intractable pain and was finally discharged home for terminal care with high doses of morphine, ketamine, and midazolam infusion through elastomeric pump attached to a peripherally inserted central catheter (PICC line). The suffering of imminently dying children should be reduced, and judicious dose escalation of opioids along with adjuvants is appropriate and often necessary. [ABSTRACT FROM AUTHOR]

We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct 'neuroinflammatory signatures'. To explore this hypothesis further, we tested whether neuroinflammatory signal can characterize putative aetiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. 'radicular' versus 'axial' back pain). Fifty-four patients with chronic low back pain, 26 with axial back pain [43.7 ± 16.6 years old (mean ± SD)] and 28 with radicular back pain (48.3 ± 13.2 years old), underwent PET/MRI with 11C-PBR28, a second-generation radioligand for TSPO. 11C-PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the 11C-PBR28 data (i) to functionally localize the primary somatosensory cortex back and leg subregions; and (ii) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of 'fibromyalgianess' (i.e. the degree of pain centralization, or 'nociplastic pain'). Furthermore, statistical mediation models were used to explore possible causal relationships between these three variables. For the primary somatosensory cortex representation of back/leg, 11C-PBR28 PET signal and functional connectivity to the thalamus were: (i) higher in radicular compared to axial back pain patients; (ii) positively correlated with each other; (iii) positively correlated with fibromyalgianess scores, across groups; and finally (iv) fibromyalgianess mediated the association between 11C-PBR28 PET signal and primary somatosensory cortex-thalamus connectivity across groups. Our findings support the existence of 'neuroinflammatory signatures' that are accompanied by neurophysiological changes and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about interindividual variability in neuroimmune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches. [ABSTRACT FROM AUTHOR]

This article examines the racial disparities in pain management for patients with hidradenitis suppurativa (HS), a chronic skin disease characterized by painful abscesses. The study analyzed data from over 79,000 patients and found that Black patients with HS were less likely to be prescribed opioids and neuropathic agents compared to White patients. The findings highlight the need for education among physicians regarding HS management and the importance of addressing biases that contribute to racial disparities in pain treatment. The study suggests further research into factors influencing prescription decisions, such as gender and implicit bias. [Extracted from the article]

Ketamine at sub-anesthetic doses is a potent analgesia. Its use in cancer pain remains equivocal with protocols varying in patient selection, starting dose, titration, duration of use and adjustment of co-analgesics. To study the impact of a standardised Ketamine Step Protocol on cancer pain in a Palliative Care Unit (PCU). This is a prospective cohort study of a standardised Ketamine Step Protocol which was developed in a PCU for use in cancer pain. The subcutaneous ketamine infusion was standardised at a starting dose of 75 mg over 24 hours with Haloperidol 5 mg as prophylaxis against psycho-mimetic side effects. Incremental doses of ketamine followed the daily stepwise protocol. Of the 48 patients analysed, 41 (85.4%) had neuropathic cancer pain. The median Palliative Performance Scale score (PPSv2) was 40%. Mean Numerical Rating Score (NRS) improved from 6.74 to 2.61 (P < 0.0001) with a mean percentage reduction of 58.05%. The final mean daily ketamine dose needed to achieve stable pain control was 137.50 mg/day (±81.54). 31(62.5%) patients achieved pain control by day 3. The mean Morphine Equivalent Daily Dose (MEDD) reduction was from 130.34 mg to 107.33 mg (P < 0.002) with a percentage reduction of 18.85%. More than half of our patients completed the 5 d protocol with mild to moderate side effects not warranting urgent medical intervention nor termination of the ketamine protocol. Use of a standardised Ketamine Step Protocol showed a statistically significant reduction in pain and MEDD in patients with predominantly neuropathic cancer pain. It also demonstrated a safe and effective method for opioid reduction after commencement of parenteral ketamine. Our study shows that: Parenteral ketamine is a potent analgesic which significantly reduced pain in patients with cancer neuropathic pain. This study also demonstrated a safe and effective method for titration of opioids after parenteral ketamine is started. Concurrent use of psychotropics also helps to reduce psycho-mimetic side effects, increasing tolerability to ketamine. [ABSTRACT FROM AUTHOR]

Background: Non-dental orofacial pain disorders are not uncommon, but idiopathic or primary facial pain syndromes are rare. Inadequate recognition of these disorders usually leads to unsatisfactory and unmet treatment needs. Methods: We conducted a narrative review with a literature search in PubMed until December 2021, focusing on current guidelines and the recently published International Classification of Orofacial Pain (ICOP). Results: In this paper, we provide an updated overview of the common orofacial pain disorders following the ICOP, covering the classification, epidemiology, pathophysiology, clinical approaches, and treatment options. Additionally, we propose a pragmatic approach focusing on the attack duration to improve distinguishing orofacial disorders. Conclusion: The introduction of ICOP offers the opportunity to better coordinate and concentrate scientific efforts, which lays the foundation for the identification of the disease mechanism of facial pain disorders and the optimization of the currently still insufficient therapeutic strategies. [ABSTRACT FROM AUTHOR]

Study Design: Prospective study. Purpose: To investigate the prevalence and the associated risk factors of chronic neuropathic pain symptoms using painDETECT questionnaire in adolescent idiopathic scoliosis (AIS) patients who underwent posterior spinal fusion (PSF) surgery. Overview of Literature: Post-lumbar surgery syndrome is a disease entity that describes neuropathic pain following spinal surgery. However, few studies have investigated the prevalence and risk factors for neuropathic pain in pediatric population undergoing corrective spinal surgery. Methods: Forty AIS patients were recruited. Demographic, preoperative, and postoperative data were recorded. The magnitude and characteristics of postoperative pain were assessed using the painDETECT questionnaire through telephone enquiries at intervals of 2, 6, 12, and 24 weeks. Statistical analyses were followed by Pearson correlation test to determine the relationship between pain scores at 6, 12, and 24 weeks with the risk factors. Results: Based on the painDETECT questionnaire, 90% of the patients had nociceptive pain, and 10% had a possible neuropathic pain component at 2 weeks postoperatively as per a mean painDETECT score of 7.1±4.5. Assessments at 6, 12, and 24 weeks showed that no patients had neuropathic pain with painDETECT scores of 4.4±3.2, 2.9±2.9, and 1.5±2.0, respectively. There was a significant correlation between total postoperative morphine use during 48 hours after the surgery and a tendency to develop neuropathic pain (p =0.022). Conclusions: Chronic neuropathic pain was uncommon in AIS patients who had undergone PSF surgery. Higher opioid consumption will increase the possibility of developing chronic neuropathic pain. [ABSTRACT FROM AUTHOR]

Motor cortex stimulation via surgically implanted electrodes has been used as an off-label treatment for chronic neuropathic pain, but its efficacy has not been fully established. We aimed to objectively study the efficacy of motor cortex stimulation and characterize potential predictors of response. In this randomized, double-blind, sham-controlled, single centre trial, we recruited 18 patients with chronic neuropathic pain who did not adequately respond to conventional treatment and had a numerical pain rating scale (NRS) score ≥6. Patients were initially assigned to receive 3 months of active ('on') or sham ('off') stimulation in a double-blind cross-over phase. This was followed by a 3-month single-blind phase, and 6 months of open-label follow-up. A meaningful response in our trial was defined as a ≥30% or 2-point reduction in NRS scores during active stimulation. Using Bayesian statistics, we found a 41.4% probability of response towards on versus off motor cortex stimulation. The probability of improvement during active stimulation (double-blind, single-blind and open-label phases) compared to baseline was 47.2-68.5%. Thirty nine per cent of the patients were considered long-term responders, 71.4% of whom had facial pain, phantom limb pain or complex regional pain syndrome. In contrast, 72.7% of non-responders had either post-stroke pain or pain associated with brachial plexus avulsion. Thirty-nine per cent of patients had a substantial postoperative analgesic effect after electrode insertion in the absence of stimulation. Individuals with diagnoses associated with a good postoperative outcome or those who developed an insertional effect had a near 100% probability of response to motor cortex stimulation. In summary, we found that ∼40% of patients responded to motor cortex stimulation, particularly those who developed an insertional effect or had specific clinical conditions that seemed to predict an appropriate postoperative response. [ABSTRACT FROM AUTHOR]

Innocuous touch sensation is mediated by cutaneous low-threshold mechanoreceptors (LTMRs). Ab slowly adapting type I (SAI) neurons constitute one LTMR subtype that forms synapse-like complexes with associated Merkel cells in the basal skin epidermis. Under healthy conditions, these complexes transduce indentation and pressure stimuli into Ab SAI LTMR action potentials that are transmitted to the CNS, thereby contributing to tactile sensation. However, it remains unknown whether this complex plays a role in the mechanical hypersensitivity caused by peripheral nerve injury. In this study, we characterized the distribution of Merkel cells and associated afferent neurons across four diverse domains of mouse hind paw skin, including a recently described patch of plantar hairy skin. We also showed that in the spared nerve injury (SNI) model of neuropathic pain, Merkel cells are lost from the denervated tibial nerve territory but are relatively preserved in nearby hairy skin innervated by the spared sural nerve. Using a genetic Merkel cell KO mouse model, we subsequently examined the importance of intact Merkel cell-Ab complexes to SNI-associated mechanical hypersensitivity in skin innervated by the spared neurons. We found that, in the absence of Merkel cells, mechanical allodynia was partially reduced in male mice, but not female mice, under sural-sparing SNI conditions. Our results suggest that Merkel cell-Ab afferent complexes partially contribute to mechanical allodynia produced by peripheral nerve injury, and that they do so in a sex-dependent manner. [ABSTRACT FROM AUTHOR]