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]

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]

In this study, we recruited 50 chronic pain (neuropathic and nociceptive) and 43 pain-free controls to identify specific blood biomarkers of chronic neuropathic pain (CNP). Affymetrix microarray was carried out on a subset of samples selected 10 CNP and 10 pain-free control participants. The most significant genes were cross-validated using the entire dataset by quantitative real-time PCR (qRT-PCR). In comparative analysis of controls and CNP patients, WLS (P = 4.80 × 10–7), CHPT1 (P = 7.74 × 10–7) and CASP5 (P = 2.30 × 10–5) were highly significant, whilst FGFBP2 (P = 0.00162), STAT1 (P = 0.00223), FCRL6 (P = 0.00335), MYC (P = 0.00335), XCL2 (P = 0.0144) and GZMA (P = 0.0168) were significant in all CNP patients. A three-arm comparative analysis was also carried out with control as the reference group and CNP samples differentiated into two groups of high and low S-LANSS score using a cut-off of 12. STAT1, XCL2 and GZMA were not significant but KIR3DL2 (P = 0.00838), SH2D1B (P = 0.00295) and CXCR31 (P = 0.0136) were significant in CNP high S-LANSS group (S-LANSS score > 12), along with WLS (P = 8.40 × 10–5), CHPT1 (P = 7.89 × 10–4), CASP5 (P = 0.00393), FGFBP2 (P = 8.70 × 10–4) and FCRL6 (P = 0.00199), suggesting involvement of immune pathways in CNP mechanisms. None of the genes was significant in CNP samples with low (< 12) S-LANSS score. The area under the receiver operating characteristic (AUROC) analysis showed that combination of MYC, STAT1, TLR4, CASP5 and WLS gene expression could be potentially used as a biomarker signature of CNP (AUROC − 0.852, (0.773, 0.931 95% CI)). [ABSTRACT FROM AUTHOR]

Purpose of Review: Researchers suggests that patients with COVID-19 develop neuropathic pain within weeks or months following infection and that patients with neuropathic pain and COVID-19 sometimes present with deterioration of neurologic complications and pain exacerbation. The objective of this systematic review is to discuss the case-reports having neuropathic pain during and after COVID-19 infection. Recent Findings: Case reports that has described about patients getting neuropathy or neuropathic pain around the disease either immediately or late post COVID were included. The data was extracted and qualitatively synthesised. Literature was searched and 939 articles were found. 12 articles were screened as per the eligibility criteria and finally, 6 case reports on neuropathic pain in Covid-19 were selected from the database and manual search and finalised for analysis. 2 cases of herpes zoster and post herpetic neuralgia, 2 cases of intense burning pain, 1 case of trigeminal neuralgia and 1 of brachial plexopathy included for the review. Summary: Covid 19 viral neurogenic invasion is something very newly discovered topic of discussion in the field of research. With the passage of time, more cases will emerge and more data will be available for research. The review is registered in Prospero with no. CRD42021257060. [ABSTRACT FROM AUTHOR]

Purpose Of Review: This article is a systematic review of data from 2018 to 2020 regarding information from publications on epidemiologic, diagnostic, and therapeutic advancements in human immunodeficiency virus-associated peripheral neuropathy.Recent Findings: The epidemiology/pathology of HIV neuropathy is discussed. Diagnostics includes skin wrinkling-eutectic mixture of local anesthetic test and neurologic examinations. Therapeutic interventions include pharmacologic and nonpharmacologic management as well as self-management strategies. Peripheral neuropathy continues to affect the lives of persons living with HIV. First-line treatment with pregabalin or gabapentin for HIV neuropathic pain has limited data on adequate response. Exercise and self-management strategies may provide benefit in pain reduction. Continuing research on risk factors and biomarkers for HIV-related peripheral neuropathy will be critical for future diagnostic and therapeutic agents. [ABSTRACT FROM AUTHOR]

Purpose: Acute pain and resting arterial blood pressure (BP) are positively correlated in patients with chronic pain. However, it remains unclear whether treatment for chronic pain reduces BP. Therefore, in a retrospective study design, we tested the hypothesis that implantation of an epidural spinal cord stimulator (SCS) device to treat chronic pain would significantly reduce clinic pain ratings and BP and that these reductions would be significantly correlated. Methods: Pain ratings and BP in medical records were collected before and after surgical implantation of a SCS device at the University of Iowa Hospitals and Clinics between 2008 and 2018 (n = 213). Results: Reductions in pain rating [6.3 ± 2.0 vs. 5.0 ± 1.9 (scale: 0–10), P < 0.001] and BP [mean arterial pressure (MAP) 95 ± 10 vs. 89 ± 10 mmHg, P < 0.001] were statistically significant within 30 days of SCS. Interestingly, BP returned toward baseline within 60 days following SCS implantation. Multiple linear regression analysis showed that sex (P = 0.007), baseline MAP (P < 0.001), and taking hypertension (HTN) medications (P < 0.001) were significant determinants of change in MAP from baseline (Δ MAP) (model R2 = 0.33). After statistical adjustments, Δ MAP was significantly greater among women than among men (− 7.2 ± 8.5 vs. − 3.9 ± 8.5 mmHg, P = 0.007) and among patients taking HTN medications than among those not taking hypertension medications (− 10.1 ± 8.7 vs. − 3.9 ± 8.5 mmHg, P < 0.001), despite no group differences in change in pain ratings. Conclusions: Together, these findings suggest that SCS for chronic pain independently produces clinically meaningful, albeit transient, reductions in BP and may provide a rationale for studies aimed at reducing HTN medication burden among this patient population. [ABSTRACT FROM AUTHOR]

Purpose Of Review: This manuscript is a systematic, narrative review that compiles and describes all data available from 2019 related to epidemiologic, diagnostic, and therapeutic advances in diabetic neuropathy (DN).Recent Findings: Epidemiology of DN is discussed. Diagnostic modalities include predictive models, electrodiagnostics, imaging, and biomarkers. A majority of studies on the treatment of diabetic peripheral neuropathy (DPN) involve pharmacotherapy, but complementary and alternative medicine, exercise, modalities, psychological, interventional, and surgical options are also explored. DN is a highly prevalent and debilitating consequence of diabetes that can present challenges to the clinician as the assessment is largely subjective with different phenotypic presentations among patients. Treatment of DN is largely symptomatic as the pathogenesis of DN is not fully understood and is likely multifactorial. It is evident from the broad range of treatments that too often provide unsatisfactory relief that there is no consensus about a single most effective treatment for DN, and monotherapy rarely proves to be successful. [ABSTRACT FROM AUTHOR]

Numerous definitions of pain have been proposed over many years with different implications when applied to clinical practice. This paper reviews information regarding the evolution of definitions of pain terminology and pain syndromes as they relate to everyday practice for clinicians and those operating within the medicolegal judicial system, both trainees and seasoned professionals, with a focus on chronic pain. An historical overview of the evolution and chronology of chronic pain labels and definitions is provided with emphasis on those used currently in clinical practice. Subsequently, the paper mainly concentrates on the two more recent revisions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) of the American Psychiatric Association (APA) and the basic principles of International Classification of Diseases (ICD) by the World Health Organization (WHO). It further provides a summary of the newly accepted WHO ICD-11 novel classification of pain disorders, a joint effort of WHO and the International Association for the Study of Pain (IASP). We conclude our review by providing our personal opinions and commentaries on controversies and dilemmas associated with the DSM, and ICD pain definitions and classifications, and offer useful tips for those who perform forensic examinations. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated sacral neuromodulation's effectiveness for managing refractory neuropathic lower urinary tract dysfunction in children and adolescents. Methods: Twenty-five children and adolescents underwent peripheral nerve evaluation test phase of sacral neuromodulation at our center. Thirteen (seven boys and six girls) cases suffered from neuropathic lower urinary tract dysfunction refractory to the maximum medical treatment. The test was done with temporary wire in all patients. Patients with more than 50% improvement in symptoms were chosen for the second stage of implantation of quadripolar tined lead and implantable pulse generator. Bowel transit symptoms were recorded before and after the surgery. Results: Eight patients (61.53%; five boys and three girls) had positive responses to the peripheral nerve evaluation test phase. They underwent implantation of permanent quadripolar tined lead and implantable pulse generator. The etiologies were lumbosacral myelomeningocele, occult spina bifida, partial sacral agenesis and incomplete spinal cord injury. Positive clinical response (> 50% improvement in symptoms) was achieved in seven (85%) at a mean follow-up of 14.25 months. Three patients became capable to stop clean intermittent catheterization (P =0.125). The 24-h pad test decreased from 484 to 78 g from before to after the surgery (P =0.043). Conclusion: This clinical study on a small sample size of children and adolescents demonstrates positive results in short-term follow-up. However, as the procedure is still not approved officially, multicenter studies with more patients can prove the safety and efficacy of sacral neuromodulation in long term among this special group of patients. [ABSTRACT FROM AUTHOR]

The search for new ligands to treat neuropathic pain remains a challenge. Recently, oxytocin has emerged as an interesting molecule modulating nociception at central and peripheral levels, but no attempt has been made to evaluate the effect of recurrent oxytocin administration in neuropathic pain. Using male Wistar rats with spinal nerve ligation, we evaluated the effects of recurrent spinal (1 nmol; given by lumbar puncture) or peripheral (31 nmol; given by intraplantar injection in the ipsilateral paw to spinal nerve ligation) oxytocin administration on pain-like behavior in several nociceptive tests (tactile allodynia and thermal and mechanical hyperalgesia) on different days. Furthermore, we used an electrophysiological approach to analyze the effect of spinal 1 nmol oxytocin on the activity of spinal dorsal horn wide dynamic range cells. In neuropathic rats, spinal or peripheral oxytocin partially restored the nociceptive threshold measured with the von Frey filaments (tactile allodynia), Hargreaves (thermal hyperalgesia) and Randall–Selitto (mechanical hyperalgesia) tests for 12 days. These results agree with electrophysiological data showing that spinal oxytocin diminishes the neuronal firing of the WDR neurons evoked by peripheral stimulation. This effect was associated with a decline in the activity of primary afferent Aδ- and C-fibers. The above findings show that repeated spinal or peripheral oxytocin administration attenuates the pain-like behavior in a well-established model of neuropathic pain. This study provides a basis for addressing the therapeutic relevance of oxytocin in chronic pain conditions. [ABSTRACT FROM AUTHOR]

Copyright of Der Schmerz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Patients suffering from neuropathic pain have a higher incidence of depression and cognitive decline. Although environment enrichment (EE) may be effective in the treatment of neuropathic pain, the precise mechanisms underlying its actions remain determined. The aim of the study was to examine the molecular mechanisms underlying the EE's beneficial effects in mice with neuropathic pain. EE attenuated the pain threshold reduction, depression-like phenotype, and memory deficit in mice after chronic constriction injury (CCI). Furthermore, EE attenuated decreased neurogenesis and increased inflammation in the hippocampus of mice with neuropathic pain after CCI. Moreover, the suppression of adult hippocampal neurogenesis by temozolomide antagonized the beneficial effects of EE on depression-like phenotype and cognitive deficit in the mice with neuropathic pain. In addition, lipopolysaccharide-induced increase in tumor necrosis factor-α (TNF-α) in the hippocampus antagonized the beneficial effects of EE for these behavioral abnormalities in mice with neuropathic pain. Knock-down of NPAS4 (neuronal PAS domain protein 4) in the hippocampus by lentivirus targeting NPAS4 blocked these beneficial effects of EE in the mice with neuropathic pain. These all findings suggest that hippocampal NPAS4 plays a key role in the beneficial effects of EE on the pain sensitivity, depression-like phenotype, and memory deficit in mice with neuropathic pain. Therefore, it is likely that NPAS4 would be a new therapeutic target for perceptional, affective, and cognitive dimensions in patients with chronic pain. [ABSTRACT FROM AUTHOR]

Introduction: Debilitating facial pain can seriously affect an individual's daily living. Given that the pathophysiology behind neuropathic and myofascial pain is not fully understood, when chronic facial pain goes undiagnosed, it has been proposed that one of the two is the likely cause. Since their discovery, glossopharyngeal neuralgia (GN) and Eagle's syndrome have been considered mostly conditions afflicting the adult population. However, when pediatric patients present with symptoms resembling GN or Eagle's syndrome, physicians are less apt to include these as a differential diagnosis simply due to the low prevalence and incidence in the pediatric population.Materials and methods: A literature review was performed with the aim to better understand the history of reported cases and to provide a comprehensive report of the anatomical variations that lead to these two conditions as well as the way these variations dictated medical and surgical management. Articles were obtained through Google Scholar and PubMed. Search criteria included key phrases such as pediatric glossopharyngeal neuralgia and pediatric Eagle syndrome. These key phrases were searched independently. PubMed was searched primarily then cross-referenced articles were found via Google Scholar. Results from non-English articles were excluded.Results: A total of 58 articles were reviewed. Most of the articles focused on adult glossopharyngeal neuralgia, and the majority was comprised of case reports. When searched via PubMed, a total of 16 articles and 2 articles returned for glossopharyngeal neuralgia and Eagle's syndrome, respectively. After criteria selection and cross-referencing, a total of seven articles were found with respect to pediatric glossopharyngeal neuralgia.Conclusions: While they are rare conditions, there are multiple etiologies that lead to the debilitating symptoms of GN and Eagle's syndrome. The clinical anatomy proved notable as multiple causes of GN and Eagle's syndrome are due to variation in the anatomy of the neurovascular structures surrounding the glossopharyngeal nerve, an elongated styloid process, a calcified stylohyoid ligament as well as a calcified stylomandibular ligament. Due to the success of different treatment modalities, the treatment of choice is dependent on clinical judgment. [ABSTRACT FROM AUTHOR]

Hereditary neuropathy with liability to pressure palsy (HNPP) has historically been considered a pain-free condition, though some people with HNPP also complain of pain. This study characterised persistent pain in people with HNPP. Participants provided cross-sectional demographic data, information on the presence of neurological and persistent pain symptoms, and the degree to which these interfered with daily life. The painDETECT and Central Sensitization Inventory questionnaires were used to indicate potential neuropathic, central sensitisation and musculoskeletal (nociceptive) pain mechanisms. Additionally, participants were asked if they thought that pain was related to/part of HNPP. 32/43 (74%) subjects with HNPP had persistent pain and experience this pain in the last week. Of those with pain, 24 (75%) were likely to have neuropathic pain and 27 (84%) were likely to have central sensitisation. All 32 participants felt that their pain could be related to/part of their HNPP. Significant negative impact of the pain was common. Pain characterisation identified neuropathic pain and/or central sensitisation as common, potential underlying processes. Pain may plausibly be directly related to the underlying pathophysiology of HNPP. Further consideration of including pain as a primary symptom of HNPP is warranted. [ABSTRACT FROM AUTHOR]

Purpose: The Edmonton Classification System for Cancer Pain (ECS-CP) has been shown to predict pain management complexity based on five features: pain mechanism, incident pain, psychological distress, addictive behavior, and cognitive function. The main objective of our study was to explore the association between ECS-CP features and pain treatment outcomes among outpatients managed by a palliative care specialist-led interdisciplinary team.Methods: Initial and follow-up clinical information of 386 eligible supportive care outpatients were retrospectively reviewed and analyzed.Results: Between the initial consultation and the first follow-up visit, the median ESAS pain intensity improved from 6 to 4.5 (p < 0.0001) and the median total symptom distress score (0-100) improved from 38 to 31 (p < 0.0001). At baseline, patients with neuropathic pain (p < 0.001) and those with at least one ECS-CP feature (p = 0.006) used a higher number of adjuvant medications. At follow-up, patients with neuropathic pain were less likely to achieve their personalized pain goal (PPG) (29 vs 72%, p = 0.015). No statistically significant association was found between increasing sum of ECS-CP features and any of the pain treatment outcomes at follow-up.Conclusion: Neuropathy was found to be a poor prognostic feature in advanced cancer pain management. Increasing sum of ECS-CP features was not predictive of pain management complexity at the follow-up visit when pain was managed by a palliative medicine specialist. Further research is needed to further explore these observations. [ABSTRACT FROM AUTHOR]

Purpose: Effective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol. Patients and methods: Patients with problematic treatment-related neuropathic pain underwent a baseline assessment using validated questionnaires, psychophysical testing, and objective functional measures. The painful area was treated with topical 1 % menthol cream twice daily. Assessments were repeated at 4-6 weeks. The primary outcome was the change in Brief Pain Inventory total scores at 4-6 weeks. Secondary outcomes included changes in function, mood and skin sensation. Results: Fifty-one patients (female/male, 32/19) were recruited with a median age of 61 (ranging from 20 to 89). The commonest aetiology was CIPN (35/51), followed by scar pain (10/51). Thirty-eight were evaluable on the primary outcome. Eighty-two per cent (31/38) had an improvement in total Brief Pain Inventory scores (median, 47 (interquartile range, 30 to 64) to 34 (6 to 59), P < 0.001). Improvements in mood ( P = 0.0004), catastrophising ( P = 0.001), walking ability ( P = 0.008) and sensation ( P < 0.01) were also observed. Conclusion: This proof-of-concept study indicates that topical menthol has potential as a novel analgesic therapy for cancer treatment-related neuropathic pain. Improvements in patient-rated measures are supported by changes in objective measures of physical function and sensation. Further systematic evaluation of efficacy is required. [ABSTRACT FROM AUTHOR]

TRPM8 has been implicated in pain and migraine based on dorsal root- and trigeminal ganglion-enriched expression, upregulation in preclinical models of pain, knockout mouse studies, and human genetics. Here, we evaluated the therapeutic potential in pain of AMG2850 (( R)-8-(4-(trifluoromethyl)phenyl)- N-(( S)-1,1,1-trifluoropropan-2-yl)-5,6-dihydro-1,7-naphthyridine-7(8H)-carboxamide), a small molecule antagonist of TRPM8 by in vitro and in vivo characterization. AMG2850 is potent in vitro at rat TRPM8 (IC against icilin activation of 204 ± 28 nM), highly selective (>100-fold IC over TRPV1 and TRPA1 channels), and orally bioavailable ( F > 40 %). When tested in a skin-nerve preparation, AMG2850 blocked menthol-induced action potentials but not mechanical activation in C fibers. AMG2850 exhibited significant target coverage in vivo in a TRPM8-mediated icilin-induced wet-dog shake (WDS) model in rats (at 10 mg/kg p.o.). However, AMG2850 did not produce a significant therapeutic effect in rat models of inflammatory mechanical hypersensitivity or neuropathic tactile allodynia at doses up to 100 mg/kg. The lack of efficacy suggests that either TRPM8 does not play a role in mediating pain in these models or that a higher level of target coverage is required. The potential of TRPM8 antagonists as migraine therapeutics is yet to be determined. [ABSTRACT FROM AUTHOR]

A 65-year-old diabetic female presented with a 3-week history of a left swollen foot after a minor inversion injury and was found to have a minimally displaced fibular fracture. Despite casting and strict instructions to remain non-weight bearing, the patient continued to bear weight and later developed a significantly more displaced fracture with a draining ulcer. This injury eventually required a tibiotalocalcaneal arthrodesis using a retrograde hindfoot nail. Neuropathy and neuropathic fractures can be devastating complications of diabetes and thus require early diagnosis and intervention because they may result in significant morbidity for the patient. Thorough assessment involving imaging, a complete history and physical examination, and tools such as a 129 Hz tuning fork and the 10 g Semmes-Weinstein monofilament are paramount to establishing an accurate initial diagnosis. These tactics aid in future follow-up of the patient's injury and can be employed in both the clinic and the emergency department. Although management remains controversial for neuropathic ankle fractures because both conservative and surgical treatment regimens have high complication rates, open reduction and internal fixation continues to be the treatment of choice once closed reduction has been attempted and fails. Education is essential because diabetic patients have compromised pain and pressure sensation, which can lead to injuries and subsequent complications of which they are simply unaware. Physicians must be diligent when evaluating the diabetic foot and be explicit when providing instructions to these patients because preventing these injuries and their complications is the best patient care available. [ABSTRACT FROM AUTHOR]

The use of functional brain imaging techniques offers the possibility of uncovering the cerebral processing of the human pain experience. In recent years, many imaging studies have focused on defining a network of brain structures involved in the processing of normal pain. Additionally, it has been shown that stimulus-evoked pain, which is a frequent symptom of neuropathic pain, causes distinct patterns of brain activation. In the present study, we quantitatively analyzed the data of previous functional imaging studies. Studies were thus collected by means of a MEDLINE query. A meta-analysis using the activation-likelihood estimation method was conducted to quantify the acquired results. We then used this data to summarize and compare the cerebral activations of (i) normal and stimulus-evoked pain, (ii) thermal and mechanical pain, (iii) different types of stimulus-evoked pain (hyperalgesia, allodynia), and (iv) clinical neuropathic and experimental pain. The results suggest the existence of distinct, although overlapping, neuronal networks related to these different types of pain. [ABSTRACT FROM AUTHOR]

Central pain is a chronic neuropathic pain disorder that develops as a direct consequence of a lesion within the central nervous system. The most common causes for central pain are vascular lesions to the brain and the spinal cord, multiple sclerosis, and spinal cord injury. Clinically, central pain typically develops with a delay after the lesion. The pain typically is localized in an area of abnormal sensitivity corresponding to the preceding central lesion. Spontaneous pain and also evoked pains can be found. Pathophysiologically, ectopic neural activity and hyperexcitability are driven by pathological facilitatory and disinhibitory processes. In addition to medical history and clinical examination, diagnosis of central pain is based on imaging and electrophysiological techniques, including quantitative sensory testing, to confirm a central lesion and for identification of the underlying disease. Management of central pain mainly based on pharmacological treatment still is a great challenge, but evidence points to efficacy of antidepressants, anticonvulsants, and opioids. [ABSTRACT FROM AUTHOR]

We describe an unusual case of a 68-year-old woman who developed acute bilateral neuropathic knee joints. The patient presented with a lower respiratory tract infection, loss of power and had altered sensation in her legs. She was diagnosed with Guillain-Barré Syndrome. After improvement of her neurology, the patient was found to have a painful, subluxed knee joints. Conservative treatment was not successful and she underwent bilateral staged constrained rotating platform total knee arthroplasties. 6 months following her most recent total knee arthroplasty, the patient has pain free movements in both her knees and mobilises with a frame. [ABSTRACT FROM AUTHOR]

Complex regional pain syndrome (CRPS) is clinically characterized by pain, abnormal regulation of blood flow and sweating, edema of skin and subcutaneous tissues, active and passive movement disorders, and trophic changes. It is classified as type I (reflex sympathetic dystrophy) and type II (causalgia). CRPS cannot be reduced to one system or to one mechanism only. In the past decades, there has been absolutely no doubt that complex regional pain syndromes have to be classified as neuropathic pain disorders. This situation changed when a proposal to redefine neuropathic pain states was recently published, which resulted in an exclusion of CRPS from neuropathic pain disorders. We analyzed the strength of the scientific evidence that supports the neuropathic nature of complex regional pain syndromes. [ABSTRACT FROM AUTHOR]

Numerous mechanisms are implicated in the perception of pain. Although many anatomical, molecular, and functional components have been identified, a comprehensive and integrated theory of pain perception has yet to be firmly established that fits the diverse clinical experience. Acute pain involves the activation of several varieties of small primary sensory neurons, collectively termed nociceptors, which have small-caliber unmyelinated or myelinated axons (C and Aδ fibers, respectively) that innervate all body tissues. They are stimulated by noxious stimuli that activate ion channels on the endings either directly or through the release of cytokines from damaged or stressed tissues. A variety of drugs successfully treats acute pain by targeting these ion channels or cytokine interactions. Paradoxically, several chronic neuropathic pain conditions are associated with a loss of small-caliber axons and have an unpredictable and poor response to current drugs, especially at doses that do not cause severe side effects. In an attempt to further an integrated theory of pain perception, this review focuses upon the presumed role of small-caliber innervation, particularly to the epidermis and cutaneous vasculature, and the clinical manifestations, diagnosis, and treatment of pathologies of this innervation. [ABSTRACT FROM AUTHOR]

Study design:A randomized, double-blind, placebo-controlled, crossover, multicenter trial. A 1-week baseline period was followed by two treatment periods of 5 weeks duration with levetiracetam increased from 500 mg b.i.d. to a maximum of 1500 mg b.i.d. separated by a 1-week washout period.Objectives:The objective of the study was primarily to evaluate the efficacy of the anticonvulsant levetiracetam in patients with spinal cord injury (SCI) at- and below-level pain and secondarily to evaluate the effect on spasm severity.Setting:Outpatients at two spinal cord units and a pain center.Methods:Patients were allowed to continue their usual pain treatment at a constant dose. The primary outcome measure was the change in median daily pain score (on a 0–10 point numeric rating scale) from 1-week baseline period to the last week of each treatment period. Secondary outcome measures included pain relief of at- and below-level pain, allodynia, spasms and spasticity.Results:A total of 36 patients with SCI at- and or below-level pain were enrolled. Of these, 24 patients completed the trial. We found no effect of levetiracetam on the primary (P=0.46) or any of the secondary outcome measures. Only two patients continued levetiracetam treatment following the trial, and one patient was still in levetiracetam treatment at the 6-month follow-up. Levetiracetam was generally well tolerated with no serious adverse events.Conclusions:Levetiracetam does not relieve neuropathic pain or spasm severity following spinal cord injury. [ABSTRACT FROM AUTHOR]

The aim of this work is to assess the usefulness of apparent diffusion coefficient (ADC) value of the brain for diagnosis of patients with Gaucher’s disease type II and type III. Prospective study was conducted upon 13 patients (nine boys and four girls aged 8 months–14 years: mean 6.1 years) with Gaucher’s disease type II and III and for age-matched control group ( n = 13). Diffusion-weighted magnetic resonance imaging using a single-shot echo-planar imaging with a diffusion-weighted factor b of 0, 500, and 1,000 s/mm2 was done for all patients and volunteers. The ADC value was calculated in ten regions of the brain parenchyma and correlated with genotyping. There was significantly lower ADC value of the cortical frontal ( P = 0.003), cortical temporal ( P = 0.04), frontal subcortical white matter ( P = 0.02), corticospinal tract ( P = 0.001), cerebellum ( P = 0.001), medulla ( P = 0.002), and midbrain ( P = 0.02) between patients and volunteers. There was significant difference in the ADC value of the frontal and temporal gray matter ( P = 0.04 and 0.05, respectively) between patients with heterozygous and homozygous gene mutation. We concluded that ADC value is a new promising quantitative imaging parameter that can be used for the detection of brain abnormalities in patients with Gaucher’s disease type II and type III and has a correlation with genotyping. [ABSTRACT FROM AUTHOR]

Objective:To provide an overview of our current understanding of the problem of neuropathic pain following spinal cord injury (SCI) and to suggest possible therapeutic options in the near future.Methods:Original research articles, reviews and book chapters on the subject of pain and SCI.Results:Neuropathic pain following SCI has presented a challenge not only for traditional concepts of how pain occurs but also for more recent conceptualizations. We have made substantial progress in identifying the common types of pain that occur following SCI, determining the prevalence and characteristics of pain, investigating some of the pathophysiological changes in the nervous system that may contribute to the presence of neuropathic SCI pain and examining the effectiveness of some treatments. However major challenges remain. We still need to reach consensus on an SCI pain taxonomy; our understanding of mechanisms and the relative contribution of changes in the periphery, spinal cord and brain is incompletely understood; there are few studies that indicate effective treatment options, particularly for neuropathic SCI pain; and treatment of the biological and psychological contributors to pain is often fragmented.Conclusion:Recent studies suggest the potential usefulness of new treatment approaches such as selective pharmacological agents, application of novel neurostimulation techniques and the use of cognitive approaches to modify the pain experience. Our increasing understanding of the problem combined with the promise of these new approaches offers hope for improved management of neuropathic pain following SCI in the near future.Spinal Cord (2009) 47, 352–359; doi:10.1038/sc.2008.136; published online 11 November 2008 [ABSTRACT FROM AUTHOR]

Following tissue injury, both peripheral and central sensory neurons can become hyperexcitable, or “sensitized.” Sensitization can lead to long-term pathological changes in pain sensation. Because many chronic pain conditions are refractory to most currently available treatments, there is great interest in identifying molecular targets that contribute to the sensitization of sensory neurons. Among these, several classes of ion channels have emerged as potential targets. Recent in vitro and in vivo studies have demonstrated a role for T-type Ca2+ channels in sensory pathways and have suggested that these channels may contribute to pain processing and sensitization. Therefore, T-type channels may represent an opportunity for the development of novel pain therapeutics and may help to address an unmet medical need. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Study design:Review.Objectives:To review published articles on the assessment, diagnosis and treatment of pain following spinal cord injury (SCI) and to synthesise evidence from these materials to formulate and propose a systematic approach to management.Methods:Relevant articles regarding the treatment of pain were identified from electronic databases using the search terms ((‘spinal cord injury’ or ‘spinal cord injuries’) and ‘pain’) and both (‘treatment’) and (‘randomised controlled trials’). Relevant articles were also identified through citations in indexed journal publications and book chapters on this topic.Results:Review of the literature indicates that there are a large variety of treatments used in the management of pain following SCI with a small number supported by strong evidence for effectiveness. A treatment algorithm is proposed based on identification of underlying pain contributors and application of appropriate treatment.Conclusion:Although there are relatively few studies clearly indicating efficacy in this population, an algorithm for the management of pain following SCI might assist to maximise our effectiveness in the treatment of this condition. It is recognised that choice of treatment is also determined by factors such as medication availability, cost and side effects as well as the preferences and characteristics of the person being treated. Nevertheless, an algorithm is proposed as a way to synthesise our current level of knowledge, identify gaps for further study and aid in the management of this difficult problem.Spinal Cord (2006) 44, 67–77. doi:10.1038/sj.sc.3101824; published online 23 August 2005 [ABSTRACT FROM AUTHOR]

The clinical usefulness of classical tricyclic antidepressants has been indicated in a variety of neuropathic pain. The role of selective serotonin reuptake inhibitors (SSRIs) is, however, controversial in pain control. The present study was aimed at evaluating the efficacy of an SSRI, fluoxetine, in neuropathic pain involving peripheral (carrageenan-induced inflammation) and central sensitization (spinal nerve ligation) in rats. Fluoxetine was also assessed for antinociceptive and antiphlogistic effect against acetic acid-induced chemonociception in mice and carrageenan-induced inflammation. Fluoxetine (100-400 μg, intraplantar administration) failed to attenuate either hyperalgesia or cold allodynia in any of the tests employed. Fluoxetine dose dependently increased paw volume in the absence or presence of an inflammatory stimulus which was not reversed by indomethacin (10 mg/kg, p.o). Fluoxetine was ineffective in reducing hyperalgesia and allodynia associated with the rat models. However, fluoxetine dose dependently decreased acetic acid-induced writhings. The results indicated that 5-HT plays a differential role in pain modulation and may not be playing a major role in the maintenance of hyperalgesia and allodynia in the rat models. [ABSTRACT FROM AUTHOR]

Copyright of Der Schmerz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)