Neuropathic Features Research Articles

Subgroup Perspectives on Chronic Pain and Its Management After Spinal Cord Injury

The present study was part of a larger mixed-methods study concerning facilitators and barriers to living with chronic pain after spinal cord injury. The agreement with themes obtained in qualitative interviews were quantified in a large online survey and overarching themes were defined by factor analysis. The present study aimed to define subgroups based on cluster analysis of the overarching themes’ factor scores and to compare the subgroups on pain-related variables. Three subgroups—high pain impact, moderate pain impact, and low pain impact—emerged. The high pain impact subgroup experienced severe pain with neuropathic pain characteristics; used pain medication, multiple coping strategies, and self-remedies; and considered information about pain and its management critical, but were not able to communicate well about their pain. The moderate pain impact subgroup carried on despite pain, considered pain information important, and used multiple approaches to manage their pain, but used less medication owing to concerns about side effects and addiction. The low pain impact subgroup considered information about pain, pain treatments, and communication regarding pain less important than the other subgroups did. This study suggests that treatment approaches need to be individually tailored not only to type of pain, but also to personal factors and preferences. PerspectivePeople who experience significant pain impact after spinal cord injury use multiple approaches to manage their pain. Many have concerns about side effects and addiction, and consider information about pain and its management, including pharmacologic, nonpharmacologic, and self-remedies, a high priority. Therefore, patients’ personal preferences may provide additional tailoring options for patient-centered treatments.

Level of readiness of chronic pain patients to practise active self-care.

Given the limited alleviation of chronic pain with pharmacological treatments, various nonpharmacological and self-care approaches are often proposed that require patients' motivation. To evaluate the level of readiness (LOR) to practise different types of active self-care among chronic pain patients. A quantitative cross-sectional survey was conducted among all chronic pain patients seeking care at the Pain Center of an academic hospital from June 2013 to March 2015. Sociodemographic data, pain characteristics, treatments and the LOR to practise active self-care were investigated. Among the 1524 eligible patients, 639 (41.9%) were included. The median pain duration was 8.5years (interquartile range=7.5). Two-thirds (63.7%) of the patients reported high pain-related disability, and 64.6% had used opioids during the previous six months. Most patients had a high (44.1%) or moderate (24.6%) LOR to practise active self-care. Multivariable multinomial regression analysis showed that independent factors associated with a high LOR were a higher level of education (relative risk ratio (RRR)=3.42, 95% confidence interval (CI): 1.90-6.13, p<0.001), unemployed status due to medical condition (RRR=2.92, 95% CI: 1.30-6.56, p=0.009), the use of dietary supplements 'against pain' (RRR=2.77, 95% CI: 1.52-5.04, p=0.001) and neuropathic pain characteristics (RRR=1.80, 95% CI: 1.40-3.12, p=0.036). Older age was a factor predicting a lower LOR (RRR=0.97, 95% CI: 0.94-0.99, p=0.039). Long-term chronic pain, severe pain-related disability and the presence of a mood disorder were not associated with a lower LOR. Most chronic pain patients, including those severely affected, indicated their readiness to practise active self-care methods. Most chronic pain patients, even those severely affected, appeared to be ready to practise active self-care therapies and we believe that further studies are needed to investigate their impact on pain and quality of life.

Prevalence of chronic pain with or without neuropathic characteristics in France using the capture-recapture method: a population-based study.

Capture-recapture methods are increasingly used to determine the prevalence of numerous chronic conditions but have never been used in the context of chronic pain (CP). This study sought to provide up-to-date estimates of the prevalence of people experiencing CP ± neuropathic characteristics in France using the capture-recapture method. In 2013 to 2015, 3 data sources were used: the French prescription drug database (D-list), the national hospital discharge database (H-list), and the French pain center database (P-list). Patients aged 18 years and older treated with analgesic drugs for ≥6 months (D-list) or with a diagnosis of CP ± neuropathic characteristics (H- and P-lists) were included. Two successive capture-recapture analyses were conducted, with log-linear regression for each analysis performed. A total of 63,557 and 9852 distinct cases of CP and chronic neuropathic pain were captured, respectively. The estimated prevalence of CP and chronic neuropathic pain in the adults ranged from 27.2% (95% confidence interval: 26.1-28.4) to 32.7% (26.0-43.3) and from 5.55% (2.89-19.0) to 7.30% (6.40-8.41), respectively. Most patients were female, median ages were 67 (55-80) and 63 (51-76) years for chronic and neuropathic pain, respectively. The analgesic drugs most frequently used in CP patients were paracetamol (62.1%), weak opioids (39.7%), and nonsteroidal anti-inflammatory drugs (32.7%), whereas in neuropathic pain patients, anticonvulsants (45.3%), tricyclic antidepressants (18.1%), and serotonin-norepinephrine reuptake inhibitors (13.3%) were more frequently used. This first electronic health record-based study on CP using the capture-recapture method revealed a high prevalence of CP, with a significant proportion of neuropathic pain patients.

Lower quality of life, lower limb pain with neuropathic characteristics, female sex, and ineffective metabolic control are predictors of depressive symptoms in patients with type 2 diabetes mellitus treated in primary care

The primary objective of this study was to identify if lower limb pain with neuropathic characteristics is predictive of depressive symptoms in patients with type 2 diabetes mellitus (T2DM) treated in primary care in Brazil. It was investigated if diabetic and non-diabetic related variables could influence depressive symptoms. A quantitative and cross-sectional study was carried out in two Basic Health Units with users of the Brazilian Public Healthcare System, who were evaluated for depressive symptoms (BDI), quality of life (QoL, SF6D), pain intensity, neuropathy (loss of plantar sensitivity—LOPPS), body composition (DEXA), biochemical tests, sociodemographic variables, and comorbidities. The patients were stratified into four groups: N+P+, N+P−, N−P+, and N−P− (N = neuropathy and P = pain). One hundred twenty-one diabetics were selected by random sampling between August 2016 and June 2017. Neuropathy affected 53.8% of these individuals, and 59.5% reported intense pain. Overall depressive symptoms scores showed a positive correlation with pain intensity and a negative correlation with QoL. Depressive symptoms were reported by 66.9% of the sample, mostly female, with better levels of cholesterol, HDL and LDL; comorbidities; worse QoL; greater intensity of pain; impaired sleep; and painful neuropathy (N+P+). The predictive factors for depressive symptoms were lower QoL, pain with neuropathic characteristics, female sex, obesity, and ineffective glycemic control. These data may contribute to the understanding of the complexity of patients with T2DM who are treated in primary care and to public policies planning of care directed at the needs of this population.

Pain in Maintenance Hemodialysis Patients: A Multicenter Study

ContextPain is a common complaint in maintenance hemodialysis (MHD) patients yet is often inadequately assessed and undertreated. ObjectivesThe objective of this study was to evaluate the prevalence, characteristics, intensity, and impact of pain in MHD patients. MethodsIn a cross-sectional study conducted between 2013 and 2015, 336 MHD patients from five hemodialysis units in hospitals owned by Clalit were interviewed and evaluated. Study tools included the Brief Pain Inventory, The Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale, and demographic and clinical characteristics. In addition, computerized pharmaceutical data were reviewed. ResultsPain was experienced by 82% of the study population (mean pain level: 7.2 ± 2.2) in the 24-hour period before the interview, while 61.5% experienced neuropathic pain characteristics. Of patients with pain, two-thirds reported being regularly treated with pain medications, while 24.5% received nondrug pain treatment. Mean pain relief due to Brief Pain Inventory was 62.5 ± 30%. In multivariate analysis, female gender, a high comorbidity index, and time on dialysis >24 months were associated with the presence of significant pain in the previous 24 hours. In addition, severe pain report was associated with female gender, depression, ≥4 painful sites, and unemployment. Finally, neuropathic pain was associated with time on dialysis >24 months, depression, ≥4 painful sites, and current intensity of pain >2. ConclusionPain is common in MHD patients and is significantly associated with female gender, comorbidity, time on dialysis, and depression. Results of this study may serve as a starting point for palliative interventions for MHD patients.

Bidirectional association between disturbed sleep and neuropathic pain symptoms: a prospective cohort study in post-total joint replacement participants.

BackgroundDisturbed sleep is strongly correlated with chronic pain. The aim of this study was to examine the association between sleep disturbance and incident joint pain focusing on neuropathic-like pain symptoms.MethodsA total of 423 individuals who had undergone total joint replacement (TJR) for osteoarthritis were assessed at the mean time of 3.6 years post-surgery and again at 5.9 years post-TJR, using the Medical Outcomes Survey sleep subscale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and painDETECT questionnaire instruments. Cox hazard ratios (HRs) and 95% confidence intervals (CIs) were computed adjusting for age, body mass index, sex, and use of hypnotic and analgesic medication.ResultsThe presence of neuropathic pain symptoms predicted incidence of disturbed sleep after adjustment for covariates and pain severity (adjusted HR [aHR] 2.01, 95% CI: 1.00–4.10; p<0.05). There was no association between joint pain and incidence of disturbed sleep when individuals with neuropathic pain symptoms at the baseline visit were excluded (aHR 1.11, 95% CI: 0.47–2.67). Disturbed sleep at baseline predicted incident neuropathic joint pain symptoms (aHR 2.75, 95% CI: 1.21–6.26; p<0.016) but had no effect on incidence of joint pain when all types of pain were considered together (aHR 0.63, 95% CI: 0.30–1.39).ConclusionThese data suggest a causal bidirectional link between sleep disturbance and joint pain with neuropathic features but not with other types of joint pain.

Place of surgery in the management of post-operative chronic pain after placement of prosthetic material based on a series of 107 cases.

The objective of this study was to evaluate the efficacy of surgical removal of prosthetic material, possibly combined with nerve release, on chronic postoperative pain following placement of prosthetic material. Single-tertiary-centre study on 107 patients managed between November 2004 and April 2016 for removal of prosthetic material responsible for postoperative chronic pain: retropubic suburethral sling (n = 32), transobturator suburethral sling (n = 50), prolapse mesh (n = 16), and hernia mesh (n = 9). The primary endpoint was at least 50% reduction of pain evaluated by a pain numerical rating scale (NRS). The mean interval between the initial operation involving placement of prosthetic material and reoperation for removal of prosthetic material was 41.2 ± 35.4 months. In all cases pain apperaed immediately following prosthetic material placement surgery. Pain presented neuropathic features in almost 30% of cases and was poorly systematized in more than one-half The mean follow-up of the study population was 8.4 ± 10.3 months. The mean pain NRS score for the overall population was seven preoperatively and three at last follow-up. At least 50% reduction of the pain NRS score was observed 67% of cases at last follow-up. During follow-up, 45% of patients experienced relapse of the disorder for which the prosthetic material was initially placed with, in particular, a 62% recurrence rate of urinary incontinence after removal of transobturator suburethral tape. Surgical removal of prosthetic material to treat chronic postoperative pain, achieved global improvement of pain in about two-thirds of cases, but with a risk of recurrence of the initial disorders.

Sex differences in neuropathic pain intensity in diabetes

IntroductionSex and gender play roles in the pain experience, such that pain is more frequent in women. Explanations for this observation range from factors related to biological sex to those related to psychosocial gender. ObjectivesTo explore neuropathic pain characteristics in females with diabetes with and without established polyneuropathy. MethodsWe compared the presence and intensity of pain in males and females in 2 separate cohorts of patients with type II diabetes, with and without established diabetic polyneuropathy. Cohort #1 was recruited prospectively, while cohort #2 was studied retrospectively. ResultsCohort #1 of 223 patients with diabetes with a relatively broad spectrum of nerve injury, showed more frequent pain in females (68% versus 53% in males), a higher frequency of additional neuropathic symptoms, and evidence of milder nerve injury. Cohort #2 of 128 patients with established diabetic polyneuropathy, showed a similar frequency of pain and additional neuropathic symptoms in both sexes. In both cohorts, females reported greater pain intensity (7.9–8.5 versus 6.8–6.9 in males, on visual analog scale). DiscussionThough nerve injury and polyneuropathy are more common in males, females with diabetes report a higher frequency and intensity of pain despite milder polyneuropathy. Prospective epidemiological studies are required in order to confirm these findings in the community setting.

A Canadian Survey of Self-Management Strategies and Satisfaction with Ability to Control Pain: Comparison of Community Dwelling Adults with Neuropathic Pain versus Adults with Non-neuropathic Chronic Pain

Background: Individuals with chronic pain with neuropathic characteristics (CPNC) describe a different pain experience compared with those with chronic pain without neuropathic characteristics (CP). Aims: The aim of this study was to describe and compare pain, self-management strategies, and satisfaction with ability to control pain between adults with CPNC versus CP. Participants: Seven hundred and ten community-dwelling adults with chronic pain participated in a cross-sectional survey. Methods: CPNC was defined as a score ≥12 on the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale. Self-management and pain control was compared between participants with CPNC and CP using frequency, percent, relative risk (RR), odds ratios (ORs), and 95% confidence intervals (CIs). Results: Participants with CPNC (188/710) reported lower socioeconomic status, poorer general health, and more intense, frequent, and widespread pain. They were more likely to use prescription medications to manage pain (adjusted OR = 2.25, CI = 1.47-3.42). They were more likely to use potentially negative strategies to ease the emotional burden of living with chronic pain, including substance use (adjusted OR = 1.58, CI = 1.06-2.35), denial (adjusted OR = 2.21, CI = 1.49-3.28), and behavioral disengagement (adjusted OR = 1.68, CI = 1.16-2.45), and they were more likely to be completely dissatisfied with their ability to control pain (RR = 1.77, CI = 1.21-2.58). Conclusions: Individuals with CPNC have distinct pain and self-management experiences compared with those with CP that may lead to negative coping strategies and dissatisfaction with ability to control pain. Therefore, self-management assessment and support should be tailored by pain condition.

Persistent pain following common outpatient surgeries in children: A multicenter study in Italy

The prevalence of persistent postsurgical pain in children is over 20% after major surgeries; however, data are scarce on the prevalence, character, and risk factors among children undergoing common ambulatory surgeries. The primary aim of this study was to evaluate the prevalence of persistent pain following pediatric ambulatory surgery at 1, 3, and 6months. Secondary aims were to identify risk factors and characterize the pain and consequences of persistent postsurgical pain. ASA I-II, ages 1 month to 16 years old, undergoing elective hypospadias repair, herniorraphy, orchiopexy, and orthopedic surgery were enrolled in a prospective, longitudinal, observational study at 3 pediatric centers in Italy. All patients received general plus regional anesthesia. Postoperative pain was evaluated using age appropriate pain scales at 1 and 3hours. At 1, 3, and 6months, pain scores were obtained and Parent's Postoperative Pain Measures (<8yo) and Child Activity Limitations Interview (>8yo) surveys were administered. About 350 patients completed the study. The prevalence of pain at 1, 3, and 6months was 24% (84/350), 6.0% (21/350), and 4.0% (14/350), respectively. Inguinal herniorraphy patients experienced significantly higher pain at all 3-time points; 35.6%, 14.9%, and 9.2%. There was no significant association between mean pain scores >4 in PACU and persistent pain. Pain persisting at 6months had neuropathic characteristics and frequently interfered with daily activities and sleep. Our data support the presence of persistent pain in pediatric patients after common surgeries. Most patients who developed persistent pain at 6months had pain at 1month. We recommend questioning at follow-up visit about persistent pain and functional impairment with follow-up until resolution.

Detection of pain with neuropathic characteristics in patients with diabetes mellitus assisted in primary care units

ABSTRACT BACKGROUND AND OBJECTIVES: There is a lack of epidemiological data on neuropathic pain in Brazil. Thus, the present study aimed to detect the presence of pain with neuropathic characteristics in people with diabetes mellitus, assisted by the Hiperdia program in Santarem-Para. METHODS: A cross-sectional study was carried out between April and November of 2016 in seven Primary Care Units of Santarem. Patients with types 1 and 2 diabetes mellitus enrolled in the Hiperdia program, who answered a clinical and sociodemographic questionnaire were included. All those who reported pain responded the Douleur Neuropathique 4 questions and the visual analog pain scale. Data were tabulated and statistically analyzed using the software Bioestat® 5.0. RESULTS: The sample consisted of 129 patients, all of whom with type 2 diabetes mellitus. Of these, 67 (51.9%) reported pain. Of these, 34.1% were detected with pain of neuropathic characteristics, with a predominance of pain in lower limbs and moderate intensity. The most reported symptoms were: tingling, pinching/needling and numbness. CONCLUSION: An expressive prevalence of people with neuropathic pain was obtained through the application of the Douleur Neuropathique 4 questions questionnaire, which proved to be an effective and easily applied tool. It is suggested that the neuropathic pain should be identified in the primary care unit and that studies with greater population coverage be performed in Santarem-Para and in the Northern region, due to the scarcity of data in Brazil.

Structural homology of myelin basic protein and muscarinic acetylcholine receptor: Significance in the pathogenesis of complex regional pain syndrome.

Complex regional pain syndrome is an extremely painful condition that develops after trauma to a limb. Complex regional pain syndrome exhibits autoimmune features in part mediated by autoantibodies against muscarinic‐2 acetylcholine (M2) receptor. The mechanisms underlying the M2 receptor involvement in complex regional pain syndrome remain obscure. Based on our recent work demonstrating that limb nerve trauma releases a potent proalgesic, immunodominant myelin basic protein fragment, our present sequence database analyses reveal an unexpected and previously undescribed structural homology of the proalgesic myelin basic protein fragment with the M2 receptor. As both complex regional pain syndrome and the proalgesic myelin basic protein activity are prevalent in females, this myelin basic protein/M2 homology presents an inviting hypothesis explaining the mechanisms of autoimmune pathogenesis and sexual dimorphism that underlies vulnerability toward developing complex regional pain syndrome and other pain states with neuropathic features. This hypothesis may aid in the development of novel diagnostic and therapeutic strategies to chronic pain.

Detection of pain with neuropathic characteristics in patients with diabetes mellitus assisted in primary care units

Detection of pain with neuropathic characteristics in patients with diabetes mellitus assisted in primary care units

Scrambler therapy in the management of somatosensory signs and symptoms related to neuropathic pain: an exploratory and prospective analysis.

Objectives: Neuropathic pain is a severe and disabling health problem, often difficult to treat and characterized by specific somatosensory signs and symptoms. The goal of this study is to detect the effect of Scrambler therapy (ST) on the reset of Neuropathic Pain Diagnostic Questionnaire (DN4), in a cohort of patients affected by intense drug-resistant neuropathic pain. Methods: Patients with chronic neuropathic pain were consecutively enrolled to receive 45-minute daily ST for an average of 10 consecutive days. Evaluation of pain intensity by Numerical Rating Scale (NRS) score and DN4 questionnaire was performed at the beginning and at the end of the treatment. Primary endpoint was to achieve a significant negativization of DN4 (DN4 <4) in the study population after 10 ST sessions. Secondary endpoints were to detect a correlation between DN4 negativization and pain intensity reduction ≥50% (patient responders), finally to analyse the impact of ST on each item of DN4 survey. Results: We prospectively treated 45 patients. Mean baseline DN4 score was 5.67 [±1.43] and fell by 50.3%, with a mean DN4 score of 2.82 [±2.18] at the end of treatment (OR 2.84; 95%CI: 2.07-3.62; p<0.0001). In 28 out of 45 (62.2%) patients we reported a negativisation of DN4 (p<0.0001). Correlation between the percentage of patient responders and patients with negativization of DN4 was statistically significant (p<0.0062). Analysing each DN4 item pre- and post-ST, we reported a significant negativization in 6 out of 10 DN4 items. Discussion: Our prospective exploratory analysis met the primary endpoint and ST seems to resolve relevant somatosensory signs and symptoms related to neuropathic pain. Based on these encouraging results, the next step will be to evaluate these neuropathic pain features with dedicated tools. (www.actabiomedica.it)

Lateral Cutaneous Nerve Entrapment Syndrome (LACNES): A previously unrecognized cause of intractable flank pain

Background and aimsChronic abdominal pain may occasionally be due to terminal endings of intercostal nerves (ACNES, abdominal cutaneous nerve entrapment syndrome) that are entrapped in the abdominal wall. Spontaneous neuropathic flank pain may also be caused by involvement of branches of these intercostal nerves. Aim is to describe a series of patients with flank pain due to nerve entrapment and to increase awareness for an unknown condition coined Lateral Cutaneous Nerve Entrapment Syndrome (LACNES). MethodsPatients possibly having LACNES (constant area of flank tenderness, small point of maximal pain with neuropathic characteristics, locoregional altered skin sensation) presenting between January 2007 and May 2016 received a diagnostic 5–10mL 1% lidocaine injection. Pain levels were recorded using a numerical rating scale (0, no pain to 10, worst possible). A >50% pain reduction was defined as success. Long term effect of injections and alternative therapies were determined using a satisfaction scale (1, very satisfied, no pain – 5, pain worse). Results30 patients (21 women, median age 52, range 13–78) were diagnosed with LACNES. Pain following one injection dropped from 6.9±1.4 to 2.4±1.9 (mean, p<0.001) leading to an 83% immediate success rate. Repeated injection therapy was successful in 16 (pain free n=7, pain acceptable, n=9; median 42 months follow-up). The remaining 14 patients received (minimally invasive) surgery (n=5) or other treatments (medication, manual therapy or pulsed radiofrequency, n=9). Overall treatment satisfaction (scale 1 or 2) was attained in 79%. Conclusions and implicationsLACNES should be considered in patients with chronic flank pain. Injection therapy is long term effective in more than half of the population.

Memantine for the treatment of general neuropathic pain: a narrative review.

Neuropathic pain (NP) is difficult to treat and is associated with a decline in quality of life. NP aetiologies are numerous and a number of pathologies display neuropathic characteristics. Of the various N-methyl-d-aspartate antagonists that are alternatives to be recommended in first-line NP treatment, memantine has the safest side-effect profile and has long been approved in Alzheimer's disease. The review covers memantine studies in postherpetic neuralgia, diabetic pain, postoperative pain, complex regional pain syndrome, chronic phantom limb pain, opioid-refractory pain and fibromyalgia. Results were inconclusive because of studies with poor levels of evidence, paucity of trials and small samples. Two recent randomized trials, however, showed significant efficacy of memantine: one demonstrated prophylactic effects against postoperative neuralgia and pain-associated psychological impairment; in the other, memantine improved pain and cognition in fibromyalgia. Both studies found no side effects or adverse events. Given the high rate of therapeutic failure in chronic states, often because of adverse events, the excellent benefit/risk ratio of memantine in these pilot studies encourages further exploration of this drug in NP prevention and in fibromyalgia in larger-scale studies.

Sensory Symptom Profiles of Patients With Neuropathic Pain After Spinal Cord Injury.

Individuals experiencing neuropathic pain (NP) after spinal cord injury (SCI) present with a variety of pain descriptors in different combinations and at different intensities. These sensory features form distinct patterns, known as sensory symptom profiles. In the present cross-sectional study, we have used a multivariate statistical method (multiple correspondence analysis) to categorize the sensory symptom profiles of a cohort of 338 patients with at-level or below-level NP after SCI. We also investigated possible associations between positive neuropathic symptoms and features of the neurological lesion. The majority of participants had a combination of pain descriptors, with 59% presenting with 3 or 4 pain subtypes. No significant associations were found between specific pain profiles and etiology or clinical degree of the neurological lesion. Furthermore, similar symptom profiles were seen in patients with at-level and below-level NP. The most frequent pattern observed in patients with cervical SCI consisted predominantly of electric shocks and tingling, without burning, pressure pain, or allodynia. Classification of SCI-NP patients into the 5 groups identified in the present study based on their distinct sensory symptom profiles may allow identification of those most likely to respond to a specific analgesic approach.

Clinical characterization and genetic analysis of Korean patients with X-linked Charcot-Marie-Tooth disease type 1.

Mutations in the gap junction protein beta 1 gene (GJB1) cause X-linked Charcot-Marie-Tooth disease type 1 (CMTX1). CMTX1 is representative of the intermediate type of CMT, having both demyelinating and axonal neuropathic features. We analyzed the clinical and genetic characterization of 128 patients with CMTX1 from 63 unrelated families. Genetic analysis revealed a total of 43 mutations including 6 novel mutations. Ten mutations were found from two or more unrelated families. p.V95M was most frequently observed. The frequency of CMTX1 was 9.6% of total Korean CMT family and was 14.8% when calculated within genetically identified cases. Among 67 male and 61 female patients, 22 females were asymptomatic. A high-arched foot, ataxia, and tremor were observed in 87%, 41%, and 35% of the patients, respectively. In the male patients, functional disability scale, CMT neuropathy score, and compound muscle action potential of the median/ulnar nerves were more severely affected than in the female patients. This study provides a comprehensive summary of the clinical features and spectrum of GJB1 gene mutations in Korean CMTX1 patients.

Prophylactic inhibition of neutrophil elastase prevents the development of chronic neuropathic pain in osteoarthritic mice

BackgroundA subset of osteoarthritis (OA) patients experience joint pain with neuropathic characteristics. Mediators such as neutrophil elastase, a serine proteinase, may be released during acute OA inflammatory flares. We have previously shown that local administration of neutrophil elastase causes joint inflammation and pain via activation of proteinase-activated receptor-2 (PAR2). The aim of this study was to examine the contribution of endogenous neutrophil elastase and PAR2 to the development of joint inflammation, pain, and neuropathy associated with monoiodoacetate (MIA)-induced experimental OA.MethodsMIA (0.3 mg/10 μl) was injected into the right knee joint of male C57BL/6 mice (20–34 g). Joint inflammation (edema, leukocyte kinetics), neutrophil elastase proteolytic activity, tactile allodynia, and saphenous nerve demyelination were assessed over 14 days post-injection. The effects of inhibiting neutrophil elastase during the early inflammatory phase of MIA (days 0 to 3) were determined using sivelestat (50 mg/kg i.p.) and serpinA1 (10 μg i.p.). Involvement of PAR2 in the development of MIA-induced joint inflammation and pain was studied using the PAR2 antagonist GB83 (5 μg i.p. days 0 to 1) and PAR2 knockout animals.ResultsMIA caused an increase in neutrophil elastase proteolytic activity on day 1 (P < 0.0001), but not on day 14. MIA also generated a transient inflammatory response which peaked on day 1 (P < 0.01) then subsided over the 2-week time course. Joint pain appeared on day 1 and persisted to day 14 (P < 0.0001). By day 14, the saphenous nerve showed signs of demyelination. Early treatment with sivelestat and serpinA1 blocked the proteolytic activity of neutrophil elastase on day 1 (P < 0.001), and caused lasting improvements in joint inflammation, pain, and saphenous nerve damage (P < 0.05). MIA-induced synovitis was reversed by early treatment with GB83 and attenuated in PAR2 knockout mice (P < 0.05). PAR2 knockout mice also showed reduced MIA-induced joint pain (P < 0.0001) and less nerve demyelination (P = 0.81 compared to saline control).ConclusionsNeutrophil elastase and PAR2 contribute significantly to the development of joint inflammation, pain, and peripheral neuropathy associated with experimental OA, suggesting their potential as therapeutic targets.

Longitudinal Perioperative Pain Assessment in Head and Neck Cancer Surgery.

To evaluate perioperative pain in patients undergoing major head and neck cancer surgery and identify associations between preoperative and postoperative pain characteristics. Patients undergoing head and neck surgery with regional/free tissue transfer were enrolled. Preoperative pain and validated screens for symptoms (neuropathic pain, anxiety, depression, fibromyalgia) were assessed. Postoperatively, patients completed a pain diary for 4 weeks. Twenty-seven patients were enrolled. Seventy-eight percent had pain prior to surgery, and for 38%, the pain had neuropathic characteristics. Thirteen patients (48%) completed at least 2 weeks of the postoperative pain diary. Patients with moderate/severe preoperative pain report significantly greater pain scores postoperatively, though daily pain decreased at a similar linear rate for all patients. Patients with more severe preoperative pain consumed greater amounts of opioids postoperatively, and this correlated with daily postoperative pain scores. Patients who screened positive for neuropathic pain also reported worse postoperative pain. Longitudinal perioperative pain assessment in head and neck patients undergoing surgery suggests that patients with worse preoperative pain continue to endorse worse pain postoperatively and require more narcotics. Patients with preoperative neuropathic pain also report poor pain control postoperatively, suggesting an opportunity to identify these patients and intervene with empiric neuropathic pain treatment.