Sciatic nerve cuffing in mice: A model of sustained neuropathic pain

Because of its severity, chronicity, resistance to usual therapy and its consequences on quality of life, neuropathic pain represents a real clinical challenge. Fundamental research on this pathology uses metabolic, pharmacological or traumatic models in rodents that reproduce the characteristic human pain symptoms. In 1996, Mosconi and Kruger morphologically described a model of peripheral neuropathy in which a cuff of polyethylene tubing was placed around the sciatic nerve in rats. In the present study, we evaluated the behavioral consequences of this neuropathic pain model in C57Bl/6J mice which is the main genetic background used for studies in transgenic mice. A short cuff of polyethylene tubing was unilaterally placed around the main branch of the sciatic nerve. It induced an ipsilateral heat thermal hyperalgesia lasting around 3 weeks, and a sustained ipsilateral mechanical allodynia lasting at least 2 months. We showed that this neuropathic pain model is insensitive to ketoprofen, a non‐steroidal anti‐inflammatory drug. Morphine treatment acutely suppressed the mechanical allodynia, but tolerance to this effect rapidly developed. The analysis of video recordings revealed that most aspects of spontaneous behavior remained unaffected on the long term, excepted for a decrease in the time spent at social interaction for the neuropathic mice. Using the elevated plus‐maze and the marble‐burying test, we also showed that neuropathic mice develop an anxiety phenotype. Our data indicate that sciatic nerve cuffing in mice is a pertinent model for the study of nociceptive and emotional consequences of sustained neuropathic pain.     

Species and strain differences in rodent sciatic nerve anatomy: implications for studies of neuropathic pain

Hindlimb pain models developed in rats have been transposed to mice, but assumed sciatic nerve neuroanatomic similarities have not been examined. We compared sciatic nerve structural organization in mouse strains (C57BL/6J, DBA/2J, and B6129PF2/J) and rat strains (Wistar, Brown Norway, and Sprague–Dawley). Dissection and retrograde labeling showed mouse sciatic nerve origins predominantly from the third lumbar (L3) and L4 spinal nerves, unlike the L4 and L5 in rats. Proportionate contributions by each level differed significantly between strains in both mice and rats. Whereas all rats had six lumbar vertebrae, variable patterns in mice included mostly five vertebrae in DBA/2J, mostly six vertebrae in C57BL/6J, and a mix in B6129PF2/J. Mice with a short lumbar vertebral column showed a rostral shift in relative contributions to the sciatic nerve by L3 and L4. Ligation of the mouse L4 nerve created hyperalgesia similar to that in rats after L5 ligation, and motor changes were similar after mouse L4 and rat L5 ligation (foot cupping) and after mouse L3 and rat L4 ligation (flexion weakness). Thus, mouse L3 and L4 neural segments are anatomically and functionally homologous with rat L4 and L5 segments. Neuronal changes after distal injury or inflammation should be sought in the mouse L3 and L4 ganglia, and the spinal nerve ligation model in mice should involve ligation of the L4 nerve while L3 remains intact. Strain-dependent variability in segmental contributions to the sciatic nerve may account in part for genetic differences in pain behavior after spinal nerve ligation.     

去势对雄性BALB/c小鼠早期血清性激素及蛋白表达等影响

目的探讨雄性小鼠去势术后早期内环境变化特点,为合理有效建立前列腺良恶性动物模型在去势与非去势的选择方面提供参考。方法选用16只BALB/c雄性小鼠,随机平均分为去势组和对照组。去势组采用经阴囊途径双睾丸切除术,对照组则作同一切口假手术。第21天所有小鼠采血处死,分别检测血清睾酮（T）、雌二醇（E2）、血管内皮生长因子（VEGF）和SELDI蛋白分析。结果与对照组相比,去势组血清T接近成倍升高（730/400）,E2反而成倍降低（112.53/256.45）,T/E2较对照组升高约4倍（6.49/1.56）;VEGF变化不明显（P〉0.05）;去势组在7个蛋白位点（3.4、5.3、7.1、11.6、11.8、15.2和15.9 KDa）有高表达,在2个位点（6.0和6.2KDa）为低表达。结论去势与否不仅对小鼠机体性激素、VEGF和蛋白表达等有影响,而且会导致在去势与否基础上所建立的前列腺良恶性模型特征不同及其研究结果差异。     

Genetic impairment of interleukin-1 signaling attenuates neuropathic pain, autotomy, and spontaneous ectopic neuronal activity, following nerve injury in mice

Peripheral nerve injury may lead to neuropathic pain, which is often associated with mechanical and thermal allodynia, ectopic discharge of from injured nerves and from the dorsal root ganglion neurons, and elevated levels of proinflammatory cytokines, particularly interleukin-1 (IL-1). In the present study, we tested the role of IL-1 in neuropathic pain models using two mouse strains impaired in IL-1 signaling: Deletion of the IL-1 receptor type I (IL-1rKO) and transgenic over-expression of the IL-1 receptor antagonist (IL-1raTG). Neuropathy was induced by cutting the L5 spinal nerve on one side, following which mechanical and thermal pain sensitivity was measured. Wild-type (WT) mice and the parent strains developed significant allodynia and hyperalgesia in the hind-paw ipsilateral to the injury compared with the contralateral hind-paw. The mutant strains, however, did not display decreased pain threshold in either hind-paw. Pain behavior was also assessed by cutting the sciatic and saphenous nerves and measuring autotomy scores. WT mice developed progressive autotomy, beginning at 7 days post-injury, whereas the mutant strains displayed delayed onset of autotomy and markedly reduced severity of the autotomy score. Electrophysiological assessment revealed that in WT mice a significant proportion of the dorsal root axons exhibited spontaneous ectopic activity at 1, 3, and 7 days following spinal nerve injury, whereas in IL-1rKO and IL-1raTG mice only a minimal number of axons exhibited such activity. Taken together, these results suggest that IL-1 signaling plays an important role in neuropathic pain and in the altered neuronal activity that underlies its development.     

Sex differences in pain anchors revisited: further investigation of "most intense" and common pain events.

Recent research suggests that the interpretation of maximal endpoints of pain scales vary between sexes. The purposes of this study were to investigate sex differences in (a) maximal endpoints of pain scales and (b) bias, discrimination, and the "better than average effect" for ratings of common pain events. Study participants described and rated the intensity of events that were the "most intense pain imaginable" for the typical woman, typical man, and one's self. Study participants also described and rated the intensity of the "most painful" events they had experienced. Study participants completed the situational pain questionnaire (SPQ), which measured the amount of pain that the typical woman, typical man, or one's self would be expected to experience during thirty common painful events. One hundred and fifteen undergraduate psychology students completed this study. Men and women differed in the categories of events selected for most intense pain imaginable for one's self. There were no significant sex differences for the intensity of most intense self-imagined pain or most painful event experienced. However, women were more likely to report the intensity of their worst self-imagined pain event as 100/100. In addition, only women demonstrated a significant correlation between the intensity of most painful self-experienced event and intensity of most intense self-imagined event. Analyses of the SPQ discrimination scores revealed no sex or version differences. Analyses of the SPQ bias scores showed that both sexes indicated that the typical woman would rate the intensity of common pain events higher than would the typical man. Women rated the intensity of common pain events for themselves lower than for the typical woman, but higher than the typical man, and men rated also rated themselves as lower than the typical women, but the same as the typical man. Thus, there was inconsistent support for the "better than average effect". Future research is needed to determine the clinical relevance of sex differences in pain anchors and gender-related stereotypes for evaluating other people's pain.     

Sex,gender, coping,and self‐efficacy: Mediation of sex differences in pain perception in children and adolescents

Sex differences in pain perception have been reported in an expanding literature based on adult samples in epidemiological as well as laboratory studies. Especially with respect to the latter, studies with children and adolescents do not consistently show that females report higher pain ratings and display lower pain tolerance than males. The first aim of the presented studies is to comparably examine sex differences in children and adolescents based on experimental and questionnaire approach indices of pain perception. The second aim is to examine the contribution of three prominent psychosocial factors (gender‐role expectations, coping with pain, and pain self‐efficacy) to these sex differences. In Study 1, a total of 118 children and adolescents from grades 5 to 9 were tested with the Cold Pressor Task (CPT) and a Pain Perception Questionnaire. In Study 2, 148 participants additionally reported on their gender‐role expectations, coping with pain, and pain self‐efficacy. Although the results reveal only medium‐sized correlations between the CPT and the questionnaire measures, both measures indicate substantial sex differences in pain perception in both studies. In Study 2, sex differences are also present for masculinity, femininity, catastrophizing as well as pain self‐efficacy. However, while the relation between sex and the CPT rating is partially mediated by pain self‐efficacy, catastrophizing partially mediates the relation between sex and the questionnaire based pain ratings. The results of both studies are discussed with respect to the difference between experimental assessments of pain perception and assessments by questionnaire in children and adolescents.     

The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: A randomised,double-blind,placebo-controlled phenotype-stratified study

In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment. This was a randomised, double-blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment periods of oxcarbazepine (1800-2400 mg) and placebo. The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11-point numeric rating scale, and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined by hypersensitivity and preserved small nerve fibre function determined by detailed quantitative sensory testing. Ninety-seven patients with peripheral neuropathic pain due to polyneuropathy, surgical or traumatic nerve injury, or postherpetic neuralgia were randomised. The intention-to-treat population comprised 83 patients: 31 with the irritable and 52 with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence interval [CI] 0.4-1.4) more than placebo (P = 0.015) and there was a significant interaction between treatment and phenotype of 0.7 (95% CI 0.01-1.4, P = 0.047). The number needed to treat to obtain one patient with more than 50% pain relief was 6.9 (95% CI 4.2-22) in the total sample, 3.9 (95% CI 2.3-12) in the irritable, and 13 (95% CI 5.3-∞) in the nonirritable nociceptor phenotype. In conclusion, oxcarbazepine is more efficacious for relief of peripheral neuropathic pain in patients with the irritable vs the nonirritable nociceptor phenotype.     

The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study.

BACKGROUND AND AIM: The aim of this randomized double blind placebo controlled study was to investigate the effectiveness and the safety of venlafaxine XR 75 and 150 mg on ongoing pain and on quantitative sensory tests in 60 patients with neuropathic pain for 8 weeks. METHODS: Evaluation parameters consisted of ongoing pain intensity (VAS), patient satisfaction, side effects, global efficacy and tolerance. Quantitative sensory measurements taken from the affected area before and after the drug treatment included pin-prick hyperalgesia, allodynia, detection and pain thresholds to electrical and heat stimuli, temporal summation of repetitive electrical and heat stimuli. RESULTS: A total of 55 patients completed the study. VAS scores decreased significantly compared to the baseline measurements in all groups. There was no significant difference between the groups regarding pain intensity and escape medication. The areas of allodynia and pin-prick hyperalgesia decreased significantly in venlafaxine groups compared to the placebo. There was no significant difference between the groups regarding the detection thresholds (electrical and heat). The pain threshold and the summation threshold to electrical stimuli and the summation threshold to heat stimuli increased significantly following treatment in both venlafaxine groups. In addition, the degree of the temporal summation to electrical and heat stimuli decreased significantly following treatment in both venlafaxine groups compared to the placebo. CONCLUSION: The study showed significant effect of venlafaxine in the manifestations of hyperalgesia and temporal summation, but not on the ongoing pain intensity. Furthermore, the quantitative sensory tests provided complementing information to the clinical measures.     

联合应用NGF、CNTF和GDNF对大鼠坐骨神经结构和功能恢复的影响

目的：探讨联合应用NGF、CNTF和GDNF对大鼠坐骨神经结构和功能恢复的影响。方法：采用大鼠坐骨神经离断模型，实验动物按NGF、CNTF、GDNF单独使用，两两组合使用，三种因子同时应用以及对照组共分为8组。测量各组坐骨神经功能指数、神经电生理参数、腓肠肌湿重恢复率、再生神经纤维形态参数。结果：三种因子联合治疗组坐骨神经功能指数、神经传导速度、动作电位波幅、腓肠肌湿重恢复最佳；除髓鞘厚度略小于NGF和CNTF联合治疗组外．神经纤维直径、再生轴突数量及神经组织面积均大于其他各组。结论：联合应用NGF、CNTF和GDNF对再生神经结构和功能恢复的作用优于其中一种因子单独使用或两种因子联合应用。     

Development of and recovery from short- and long-term low back pain in occupational settings: A prospective cohort study

Using the data of the EuroBack Unit prospective cohort study, this paper investigated the role of work-related physical factors and psychological variables in predicting the development of and recovery from short-term and long-term LBP. At baseline, 1294 predominantly male industrial workers from 10 companies in Belgium and the Netherlands filled in questionnaires. At follow-up, data from 812 employees were available. Odds ratios (ORs) were calculated using simple and multiple logistic regression analyses. For those workers reporting 0 days LBP in the year prior to baseline, negative affectivity (OR 1.06, 95% CI 1.01-1.11) was a risk factor for the development of short-term LBP (=1-30 days total of LBP in the year prior to follow-up). For those who reported 1-30 days total of LBP in the year prior to baseline, only high fear of (re)injury due to movement (OR 1.07, 95% CI 1.02-1.12) increased the risk for failure to recovery from short-term LBP. For the development of long-term LBP (=more than 30 days total of LBP in the year prior to follow-up), a significant increased risk was observed among workers with high pain severity (OR 1.19, 95% CI 1.01-1.40) and with pain referred to the ankles or feet (OR 2.92, 95% CI 1.09-7.83). The risk was reduced by social support of co-workers (OR 0.73, 95% CI 0.59-0.92) and by manual handling of materials (OR 0.63, 95% CI 0.46-0.85). For those who reported more than 30 days total of LBP in the year prior to baseline, high pain severity (OR 1.18, 95% CI 1.04-1.34) increased the risk for failure to recovery from long-term LBP. Results are compared to the baseline study (Gheldof et al., 2005) and discussed in relation with prospective studies.     

Quality of life and pain perception in alcohol dependence: A comparative examination of patients,their relatives,and healthy controls

Objective: The aim of this study was to investigate how quality of life and the perception of pain are affected by patients with alcohol dependence and their relatives compared with healthy controls. Methods: Fifty patients with alcohol dependence, 50 first-degree relatives of patients with alcohol dependence, and 50 healthy controls were included. Participants were evaluated with a questionnaire form of sociodemographic characteristics, and the World Health Organization Quality of Life–Bref-Turkish form (WHOQOL-BREF-TR). They were then given a noxious stimulus using a transcutaneous electrical nerve stimulation (TENS) device. After that, pain threshold, pain tolerance, and visual analog scale (VAS) scores of the participants were measured. Results: Patients’ quality of life was poorer than the relative and control groups. The age of first alcohol use was found to be positively associated with quality of life. Pain tolerance was found to be higher in the patients than in the controls. We found no relationship between pain perception and characteristics of addiction. Conclusions: In this study, pain tolerance was found to be higher in patients with alcohol dependence, and the characteristics of addiction did not seem to affect pain perception.     

Influence of greater occipital nerve block on pain severity in migraine patients: A systematic review and meta-analysis

Aims

Greater occipital nerve (GON) block may be a promising approach to treat migraine. However, the results remained controversial. We conducted a systematic review and meta-analysis to explore the efficacy of GON block in migraine patients.

Effects of patellar taping on knee pain,functional disability,and patellar alignments in patients with patellofemoral pain syndrome: A randomized clinical trial

Question

What are the effects of patellar taping on pain, functional disability and patellar alignments in Patellofemoral Pain Syndrome (PFPS)?

The immediate effect of lumbopelvic manipulation on knee pain,knee position sense,and balance in patients with patellofemoral pain: A randomized controlled trial

BackgroundPatellofemoral pain (PFP) is a common musculoskeletal disorder. Quadriceps and core muscle neuromuscular control impairments are frequently associated with PFP. Lumbopelvic manipulation (LPM) has been shown to improve quadriceps and core muscle activation and decrease their inhibition, but changes in balance and knee joint position sense (JPS) after this intervention remain unknown.ObjectiveTo determine whether LPM decreases knee pain and JPS error and increases balance performance in patients with PFP.DesignRandomized controlled trial.SettingBiomechanics laboratory at a rehabilitation science research center.MethodsForty-four patients with PFP participated in this study that randomly divided into two equal groups. One group received LPM and the other received sham LPM (positioning with no thrust) in a single session. At baseline and immediately after the intervention, the outcomes of pain using a visual analog scale, balance using the modified star excursion balance test (mSEBT), and JPS at 20° and 60° of knee flexion using a Biodex dynamometer.ResultsThere was a statistically significant improvement in pain, balance control (anterior direction) and JPS in the LPM group immediately after the intervention. In addition, we observed significant differences between groups in pain, balance control (anterior direction) and JPS at 60° of knee flexion immediately after the intervention.ConclusionA single session of LPM immediately improved balance control, knee JPS, and pain in patients diagnosed with PFP.Clinical rehabilitation impactFindings suggest that LPM may be used as a therapeutic tool for immediate improvement of symptoms of PFP. However, more research is needed to determine long term results.     

Effect of adding stretching to standardized procedures on cervical range of motion,pain, and disability in patients with non-specific mechanical neck pain: A randomized clinical trial

Objectiveto investigate the benefit of adding stretching exercises to cervical joint mobilization and active rotation exercises for patients with non-specific mechanical neck pain.MethodsThirty-eight subjects with non-specific mechanical neck pain were randomly assigned to a standard procedure group (passive cervical mobilization and active cervical rotation range of motion exercise) or a combined procedure (passive cervical mobilization, active cervical rotation range of motion exercises, and stretching procedures). Mixed factorial analysis of variance was used to compare changes between groups over time in active cervical range of motion, Numeric Pain Rating Scale, Neck Disability Index, Global Rating of Change, and Pressure Pain Threshold.ResultsThere was a significant change in mean active range of motion in all directions, Pressure Pain Threshold, perceived pain, disability levels, and global rating of change over time (p < 0.001). There was a significant group by time interaction in mean active range of motion during extension (p = 0.01), right rotation (p = 0.004), right and left lateral flexion (p = 0.05, and p = 0.02 respectively). However, there was no significant group by time interaction in mean active range of motion during flexion, left rotation, pain intensity (p = 0.09), right and left pressure pain threshold (p = 0.30, 0.47, respectively), and disability (p = 0.07).ConclusionsBoth study groups improved significantly in all subjective and objective outcome measures. However, data from this study suggest that adding stretching to the standard procedures may be more effective than the standard procedure alone at improving cervical extension, right rotation, and lateral flexion active range of motion, but not pain and disability.     

Short-term effectiveness of an intervention targeting lower limb range of motion on pain and disability in patellofemoral pain patients: A randomized,non-concurrent multiple-baseline study

IntroductionPatellofemoral pain (PFP) is a common and often long-standing musculoskeletal condition. Evidence of the effectiveness of interventions addressing soft tissue flexibility is conflicting and of inconsistent scientific quality. However, reduced soft tissue flexibility can negatively affect patellofemoral joint kinematics. Lower limb range of motion (LLROM) reflects soft tissue flexibility throughout the kinetic chain. The aim was to evaluate the short-term effectiveness of an intervention targeting LLROM on pain and disability in patients with PFP.MethodsA randomized, non-concurrent, multiple-baseline single-case design with a two-week intervention phase and baseline and postintervention phase with varying length was conducted. Eight participants (5 females, 3 males) of age 19(±1.6) years, weekly sports participation 12(±3.1) hours and 17(±14) months symptom duration were included. The Anterior Knee Pain Scale – Dutch Version (AKPS-DV) and the Patient Specific Complaint Scale (PSCS) were administered twice a week. After allocating participants to one of four subgroups of reduced LLROM the intervention was applied. The intervention consisted of soft tissue techniques (mobilization, taping, and stretching).ResultsParticipant 3 and 6 showed a medium and small but statistically significant positive effect on the AKPS-DV. Participant 2 showed a large and statistically significant positive effect on the PSCS.ConclusionsThis study provides moderate evidence that an intervention targeting LLROM in patients with PFP reduces pain and disability in the short-term. Further research is needed to evaluate the long-term effectiveness and optimize individual treatment outcomes.