The need for improved treatments for chronic pain has driven increased interest in cannabis-based therapeutics. Peripheral dorsal root ganglion (DRG) neurons, including nociceptors, express cannabinoid receptors (CB1 and CB2), suggesting that modulation of DRG excitability may provide an effective strategy for peripheral analgesia. Here, we investigated the effects of cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), terpene mixtures as well as cannabis plant extracts on neuronal excitability in small-diameter mouse DRG neurons using whole-cell current-clamp electrophysiology and assessed potential synergistic interactions. Both CBD and THC produced a concentration- and time-dependent inhibition of rheobase-evoked action potential firing, which were reversible in the presence of bovine serum albumin (BSA), both with similar estimated IC50 values of 5 micromolar (Terpene mixtures, as well as individual terpenes (linalool, beta-pinene, and myrcene), similarly reduced neuronal firing. Co-application of CBD with THC or terpenes enhanced inhibition, consistent with synergistic interactions and the known entourage effect. Application of WIN55,212-2 (WIN), a non-selective cannabinoid receptor agonist, in the presence of CBD also accelerated the time-dependent inhibition of neuronal firing. The inhibition of firing by the CB2-selective inverse agonist JTE-907 indicated the presence of CB2 receptors on DRG neurons. Plant extracts from the Cannabis sativa leaves also reversibly inhibited neuronal firing. CBD and a terpenes mixture produced modest effects on hERG channels, whereas plants extracts had negligible effects. Collectively, these findings demonstrate that phytocannabinoids and terpenes suppress peripheral sensory neuron excitability via receptor-dependent and indirect mechanisms, supporting their potential as non-opioid analgesics. Their synergistic interactions suggest that multi-component formulations may enhance analgesic effects.

Abstract Introduction: Whiplash-associated disorder grade II (WADII) is characterised by persistent pain in the absence of frank nerve injury, yet its molecular mechanisms remain unclear. Objectives: To identify molecular signatures of 2 recovery groups characterised by persistent moderate/severe and minimal symptoms in WADII using RNA-sequencing of blood samples 6 months postinjury. Methods: We performed bulk transcriptional analyses on blood samples collected from the primary cohort of individuals with WADII 6 months postinjury (n = 15/recovery group). Findings were replicated through meta-analyses using an independent cohort of chronic WAD. Blood cellular composition was estimated via deconvolution analyses across both cohorts. Results: Although there were no differentially expressed genes between recovery groups, we identified sex-specific gene expression signatures of recovery. In the primary WADII cohort, HLA-DQA1, HEBP1, and NECTIN2 showed lower expression in females with moderate/severe symptoms compared with minimal symptoms. SLC12A1 and MXRA7 showed lower expression in males with moderate/severe pain, whereas HLA-G was upregulated. Gene expression meta-analysis in females identified 6 differentially expressed genes, including replication of lower HLA-DQA1 expression from the primary cohort. There were no differentially expressed genes in the meta-analyses in males or between recovery groups. Deconvolution analyses revealed diverging trends between sexes for blood cell types and whiplash symptom severity scores. Ligand–receptor pair analyses further suggested distinct sex-specific recovery trajectories. Conclusion: Transcriptional profiling revealed sex-specific molecular blood signatures associated with persistent whiplash symptoms 6 months postinjury. Future research is needed to further characterise sex-specific mechanisms after whiplash injury to improve prognosis and targeted management strategies.

Whiplash injury is associated with high socioeconomic costs and poor prognosis. Most people are classified as having whiplash-associated disorder grade II (WADII), with neck complaints and musculoskeletal signs, in the absence of frank neurological signs. However, evidence suggests that there is a subgroup with underlying nerve involvement in WADII, such as peripheral neuroinflammation. This study aimed to investigate the presence of neuroinflammation in acute WADII using T2-weighted magnetic resonance imaging of the brachial plexus, dorsal root ganglia and median nerve, and clinical surrogates of neuroinflammation: heightened nerve mechanosensitivity (HNM), raised serum inflammatory mediators, and somatosensory hyperalgesia. One hundred twenty-two WADII participants within 4 weeks of whiplash and 43 healthy controls (HCs) were recruited. Magnetic resonance imaging T2 signal ratio was increased in the C5 root of the brachial plexus and the C5-C8 dorsal root ganglia in WADII participants compared with HCs but not in the distal median nerve trunk. Fifty-five percent of WADII participants had signs of HNM. Inflammatory mediators were also raised compared with HCs, and 47% of WADII participants had somatosensory changes on quantitative sensory testing. In those WADII individuals with HNM, there was hyperalgesia to cold and pressure and an increased proportion of neuropathic pain. Many people with WADII had multiple indicators of neuroinflammation. Overall, our results present a complex phenotypic profile for acute WADII and provide evidence suggestive of peripheral neuroinflammation in a subgroup of individuals. The results suggest that there is a need to reconsider the management of people with WADII.

National Clinical Guidelines recommend an integrated combination of conservative management strategies for sciatica. However, the efficacy of such combinations have not been established. The purpose of this systemic review with meta-analysis was to determine the efficacy of combined conservative (non-pharmacological) compared to single interventions for people with sciatica with a confirmed neuropathic mechanism. The systematic review was registered on PROSPERO CRD42023464011. The databases included were the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), Embase, PubMed, Scopus, APA PsycINFO, and grey literature sources from inception until January 2024. Inclusion criteria were randomized controlled trials that assessed the effectiveness of combined non-pharmacological interventions in comparison to a control intervention among individuals with sciatica of a neuropathic origin identified using diagnostic or clinical tests. Primary outcomes were back pain, leg pain, and disability. The secondary outcome was global rating of change. Study selection, data extraction and risk of bias assessment (using Cochrane ROB2) were assessed by two reviewers. Meta-analysis was performed with a random effects model with inverse variance weighting used for the metanalysis using SPSS v 29. 3,370 articles were identified, of which 6 were included. Risk of bias was high in one study and had some concerns in the remaining 5 studies for each outcome measure. There was evidence of efficacy for combined interventions for back pain in the short-and long-term (SMD − 0.56 (95

Whiplash-associated disorders (WADs) affect 20-50 million individuals globally each year, with ≤50% developing persistent pain. WAD grade II (WADII) is the most common type and is characterized by neck symptoms and musculoskeletal signs without apparent nerve injury on routine diagnostic testing. However, emerging evidence suggests that nerve pathology might be present in some people with WADII. This longitudinal cohort study aimed to investigate comprehensively the presence, temporal patterns and prognostic value of nerve pathology and neuropathic pain in acute WADII. A prospective longitudinal cohort study was conducted with 129 acute participants with WADII (median age 36.0 years, 58% female) and 36 healthy controls (median age 39.0 years, 61% female). Participants with WADII were recruited within 4 weeks of injury from local emergency departments. Data collection included bedside neurological assessments, quantitative sensory testing, intraepidermal nerve fibre density and serum neurofilament light chain concentrations. Follow-up assessments were conducted 6 months after injury. Signs of neuropathic pain were present in 65% (84/129) acutely and persisted in 32% (21/66) 6 months post-injury. Bedside neurological assessment revealed that somatosensory loss-of-function was present in 54% (70/129) acutely, reducing to 25% (17/67) 6 months post-injury. Quantitative sensory testing demonstrated significantly reduced cold, warm, thermal sensory limen, mechanical and vibration detection thresholds in acute WADII compared with controls (d > 0.47). Acute loss-of-function in at least one quantitative sensory testing parameter was present in 67.6% (85/126) of WADII. At 6 months, participants with WADII showed persistent hypoaesthesia to warm, thermal sensory limen and mechanical detection thresholds, and decreased mechanical pain and pressure pain sensitivity compared with controls (d > 0.44). These functional neurological changes were accompanied by elevated serum neurofilament light chain levels in acute WADII compared with controls [d = -0.52 (95% confidence interval -0.94, -0.10)]. Intraepidermal nerve fibre densities at the index finger were not significantly different between groups. However, dermal myelin basic protein+/protein gene product+ myelinated nerve bundles at the index finger were reduced 6 months post-injury in WADII compared with controls [d = 0.69 (0.26, 1.11)]. Multivariable linear regression suggested that bedside tests for hypoaesthesia at the index finger were prognostic for whiplash-related upper quadrant pain 6 months post-injury (r2 = 0.13, P = 0.02). In conclusion, two-thirds of participants with acute WADII initially exhibited signs of neuropathic pain and nerve pathology. At the 6-month follow-up, neuropathic pain persisted in one-third of participants with WADII, and nerve pathology persisted in two-thirds. These findings challenge the traditional musculoskeletal classification of WADII and underscore the need for targeted neurological assessments and treatment.

ABSTRACT:Whiplash injuries cause considerable pain and disability. Most individuals are diagnosed with whiplash-associated disorder grade II (WADII), which is defined by the absence of frank nerve injury. However, studies indicate possible peripheral neuroinflammation in some individuals with WADII that may contribute to symptoms. The temporal changes of peripheral neuroinflammation in WADII remain unclear. This study aimed to investigate the course of peripheral neuroinflammation from acute to chronic stages and assess whether neuroinflammation in the acute stage predicts recovery 6 months postinjury. Sixty-two WADII participants, who were examined within 4 weeks of a whiplash injury, returned for a follow-up appointment at 6 months. Thirty-two percent (n = 20) of participants considered themselves to be all better at 6 months based on a global recovery question. Magnetic resonance imaging T2-weighted signal ratio of the C5 to C8 roots of the brachial plexus, associated dorsal root ganglia, and median nerve, were similar at both time points. Signs of heightened nerve mechanosensitivity reduced significantly at 6 months, as did mechanical and thermal hyperalgesia in the upper limb. Inflammatory mediator serum levels were unaltered at 6 months, except for tumour necrosis factor-α, which was reduced. Multivariable regression analysis indicated that heightened nerve mechanosensitivity (reduced elbow range of motion) in the acute stage was weakly prognostic for neuropathic pain classification at 6 months. Although many participants recovered at 6 months, the data show that peripheral neuroinflammation may persist in some individuals. These findings highlight the complexity of WADII and the contribution of neuroinflammation in both acute and chronic stages.

Work-related musculoskeletal disorders associated with intense repetitive tasks are highly prevalent. Painful symptoms associated with such disorders can be attributed to neuropathy. In this study, we characterized the neuronal discharge from the median nerve in rats trained to perform an operant repetitive task. After 3-weeks of the task, rats developed pain behaviors and a decline in grip strength. Ongoing activity developed in 17.7% of slowly conducting neurons at 3-weeks, similar to neuritis. At 12-weeks, an irregular high frequency neuronal discharge was prevalent in >88.4% of slow and fast conducting neurons. At this time point, 8.3% of slow and 21.2% of fast conducting neurons developed a bursting discharge, which, combined with a reduction in fast-conducting neurons with receptive fields (38.4%), is consistent with marked neuropathology. Taken together, we have shown that an operant repetitive task leads to an active and progressive neuropathy that is characterized by marked neuropathology following 12-weeks task that mainly affects fast conducting neurons. Such aberrant neuronal activity may underlie painful symptoms in patients with work-related musculoskeletal disorders. Perspective: Aberrant neuronal activity, similar to that reported in this study, may contribute to upper limb pain and dysfunction in patients with work-related musculoskeletal disorders. In addition, profiles of instantaneous frequencies may provide an effective way of stratifying patients with painful neuropathies. (C) 2021 The Author(s). Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc.

Introduction Whiplash-associated disorder grade 2 (WAD2) is characterised by musculoskeletal pain/tenderness but no apparent nerve injury. However, studies have found clinical features indicative of neuropathy and neuropathic pain. These studies may indicate peripheral nerve inflammation, since preclinical neuritis models found mechanical sensitivity in inflamed, intact nociceptors. The primary aim of this study is to establish the contribution of peripheral neuroinflammation to WAD2 and its role in prognosis. Participants will be invited to participate in a sub-study investigating the contribution of cutaneous small fibre pathology to WAD2. Methods and analysis 115 participants within 1 month following whiplash injury and 34 healthy control participants will be recruited and complete validated questionnaires for pain, function and psychological factors. Data collection will take place at the Universities of Sussex and Oxford, UK. Clinical examination, quantitative sensory testing and blood samples will be undertaken. MRI scans using T2-weighted and diffusion tensor images of the brachial plexus and wrist will determine nerve inflammation and nerve structural changes. Skin biopsies from a substudy will determine structural integrity of dermal and intraepidermal nerve fibres. At 6 months, we will evaluate recovery using Neck Disability Index and a self-rated global recovery question and repeat the outcome measures. Regression analysis will identify differences in MRI parameters, clinical tests and skin biopsies between participants with WAD2 and age/gender-matched controls. Linear and logistic regression analyses will assess if nerve inflammation (MRI parameters) predicts poor outcome. Mixed effects modelling will compare MRI and clinical measures between recovered and non-recovered participants over time. Ethics and dissemination Ethical approval was received from London-Brighton and Sussex Research Ethics Committee (20/PR/0625) and South Central—Oxford C Ethics Committee (18/SC/0263). Written informed consent will be obtained from participants prior to participation in the study. Results will be disseminated through publications in peer-reviewed journals, presentations at national/international conferences and social media. Trial registration number NCT04940923 .

There is no clear understanding of the mechanisms causing persistent pain in patients with whiplash-associated disorder (WAD). The aim of this systematic review was to assess the evidence for nerve pathology and neuropathic pain in patients with WAD. EMBASE, PubMed, CINAHL (EBSCO), and MEDLINE were searched from inception to September 1, 2020. Study quality and risk of bias were assessed using the Newcastle-Ottawa Quality Assessment Scales. Fifty-four studies reporting on 390,644 patients and 918 controls were included. Clinical questionnaires suggested symptoms of predominant neuropathic characteristic in 34% of patients (range 25%-75%). The mean prevalence of nerve pathology detected with neurological examination was 13% (0%-100%) and 32% (10%-100%) with electrodiagnostic testing. Patients independent of WAD severity (Quebec Task Force grades I-IV) demonstrated significantly impaired sensory detection thresholds of the index finger compared with controls, including mechanical (SMD 0.65 [0.30; 1.00] P < 0.005), current (SMD 0.82 [0.25; 1.39] P = 0.0165), cold (SMD -0.43 [-0.73; -0.13] P = 0.0204), and warm detection (SMD 0.84 [0.25; 1.42] P = 0.0200). Patients with WAD had significantly heightened nerve mechanosensitivity compared with controls on median nerve pressure pain thresholds (SMD -1.10 [-1.50; -0.70], P < 0.0001) and neurodynamic tests (SMD 1.68 [0.92; 2.44], P = 0.0004). Similar sensory dysfunction and nerve mechanosensitivity was seen in WAD grade II, which contradicts its traditional definition of absent nerve involvement. Our findings strongly suggest a subset of patients with WAD demonstrate signs of peripheral nerve pathology and neuropathic pain. Although there was heterogeneity among some studies, typical WAD classifications may need to be reconsidered and include detailed clinical assessments for nerve integrity.

BACKGROUND:A segmental, contra-lateral cervical lateral glide (CCLG) mobilization technique is effective for patients with cervical radiculopathy (CR). The CCLG technique induces median nerve sliding in healthy individuals, but this has not been assessed in patients with CR. OBJECTIVE:This study aimed to 1) assess longitudinal excursion of the median nerve in patients with CR and asymptomatic participants during a CCLG movement, 2) reassess nerve excursions following an intervention at a 3-month follow-up in patients with CR and 3) correlate changes in nerve excursions with changes in clinical signs and symptoms. DESIGN:Case-control study. METHODS:During a computer-controlled mechanically induced CCLG, executed by the Occiflex™, longitudinal median nerve excursion was assessed at the wrist and elbow with ultrasound imaging (T0) in 20 patients with CR and 20 matched controls. Patients were re-assessed at a 3-month follow-up (T1), following conservative treatment including neurodynamic mobilization. RESULTS:There was a significant difference between patients and controls in the excursion of the median nerve at both the wrist (Mdn = 0.50 mm; IQR = 0.13-1.30; 2.10 mm (IQR = 1.42-2.80, p < 0.05)) and elbow (Mdn = 1.21 mm (IQR = 0.85-1.94); 3.49 mm (IQR = 2.45-4.24, p < 0.05)) respectively at T0. There was also a significant increase in median nerve excursion at both sites between T0 and T1 in those with CR (Mdn = 1.96, 2.63 respectively). Wilcoxon Signed-Ranks Test indicated median pre-test ranks (Mdn = 0.5, 1.21; Z = - 3.82, p < 0.01; Z = -3.78, p < 0.01 respectively) and median post-test ranks. There was a strong correlation between improvement in median nerve excursion at the elbow at T1 and improvement in pain intensity (r = 0.7, p < 0.001) and functional limitations (r = 0.6, p < 0.01). CONCLUSION:Longitudinal median nerve excursion differs significantly between patients with CR and asymptomatic volunteers at baseline, but this difference is no longer present after 3 months of conservative physiotherapy management. Improvement in nerve excursion correlates with improvement in clinical signs and symptoms.

Radiating pain is a significant feature of chronic musculoskeletal pain conditions such as radiculopathies, repetitive motion disorders and whiplash associated disorders. It is reported to be caused by the development of mechanically-sensitive ectopic receptive fields along intact nociceptor axons at sites of peripheral neuroinflammation (neuritis). Since inflammation disrupts axonal transport, we have hypothesised that anterogradely-transported mechanically sensitive ion channels accumulate at the site of disruption, which leads to axonal mechanical sensitivity (AMS). In this study, we have characterised the mechanical properties of the ectopic axonal receptive fields in the rat and have examined the contribution of mechanically sensitive ion channels to the development of AMS following neuritis and vinblastine-induced axonal transport disruption. In both models, there was a positive force-discharge relationship and mechanical thresholds were low (similar to 9 mN/mm(2)). All responses were attenuated by Ruthenium Red and FM1-43, which block mechanically sensitive ion channels. In both models, the transport of TRPV1 and TRPA1 was disrupted, and intraneural injection of agonists of these channels caused responses in neurons with AMS following neuritis but not vinblastine treatment. In summary, these data support a role for mechanically sensitive ion channels in the development of AMS. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

Experiments in cadavers have demonstrated significant mechanical interactions between constituents of myofascial chains. However, evidence for such force transmission effects is scarce under in vivo conditions. The purpose of this trial was to examine the impact of ankle motion on soft tissue displacement of the dorsal thigh. Eleven healthy active individuals (26.8 ± 4.3 years, six males), in prone position and with the knee extended, underwent passive calf stretches (ankle dorsal extension) imposed by an isokinetic dynamometer. High-resolution ultrasound was used to simultaneously capture the displacement of the semimembranosus muscle, which was quantified by means of cross-correlation analysis. Inactivity of the leg muscles was controlled using surface electromyography (EMG). One participant had to be excluded due to major EMG activity during the experiment. According to a one-sample t test testing the difference to the neutral zero position, ankle dorsal extension induced substantial caudal muscle displacements (5.76 ± 2.67 mm, p < 0.0001). Correlation analysis (Spearman), furthermore, revealed a strong association between maximal dorsal extension and semimembranosus motion (rho = 0.76, p = 0.02). In conclusion, the present trial provides initial in vivo evidence for a mechanical force transmission between serially connected skeletal muscles. This means that local alterations of the mechanical tissue properties may modify flexibility in neighboring (superior or inferior) joints.

Purpose: The incidence and socioeconomic consequences of whiplash associated disorder appear undiminished. Approximately 30-50% of patients develop chronicity, and the majority of patients are diagnosed with grade II whiplash associated disorder (WAD II). Patients frequently present with cutaneous hypersensitivities and hypoesthesia but without obvious clinical sign of nerve injury. T2-weighted magnetic resonance imaging (MRI) can be used to identify neuropathy. It is reported that an increased T2 signal indicates nerve oedema as a consequence of inflammatory and vascular changes.

Ultrasound is an important tool for teaching anatomy, it provides students with a live window into the body so that functional anatomy can be viewed in real‐time. Importantly, ultrasound provides a clinically relevant approach to learning anatomy. At Brighton and Sussex Medical School, ultrasound has been fully integrated into year 1 and 2 of the MBBS medical curriculum in small group teaching sessions (n = 15), that total 12 hours. To determine the usefulness of ultrasound for teaching anatomy, students completed an evaluation questionnaire consisting of 15 questions following each systems‐based module in year 1 for the 2014/15 and 2017/18 cohorts. All responses (n = 49–90) were scored on a five‐point Likert scale. Two focus groups (n=13 students) explored students' perceptions. Thematic analysis highlighted themes of respect and empathy for the patient, and concerns over the impact if no one volunteered. Students also reported the helpfulness of ultrasound for aiding interpreting 3D and radiological images. Student's responses to survey reveal: that they see why ultrasound is relevant to practice, felt it helped them to comprehend the 3D nature of the human body and helped their understanding of surface anatomy. However, students felt less proficient using ultrasound as the course progresses (P=<0.05) and they found it more difficult to examine the heart (P=<0.001). Student's ability to recognize vessels increased as the year progressed (P=<0.001.). In summary, interpretation of an ultrasound image can be challenging for students. In particular, students find it difficult to orientate a 2D slice through organs such as the heart, which is largely because small adjustments in probe orientation can result in unfamiliar views. Students clearly understand the clinical relevance of ultrasound. With increasing use of ultrasound in clinics, early exposure will undoubtedly help prepare students for clinical practice. Finally, this work clearly emphasises the need for better learning resources in this field.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

In The Mill on the Floss,1Eliot G The mill on the floss. William Blackwood and Sons, Edinburgh1860Crossref Google Scholar George Eliot wrote “But the immediate presence of this disgrace was so much keener an experience to Tom than the worst form of apprehension, that he felt at this moment as if his real trouble had only just begun: it was a touch on the irritated nerve compared with its spontaneous dull aching.” The author used current understandings of physical pain symptoms as a metaphor for personal psychological suffering. Tom knew that his father had lost their property and carried that embarrassment with him (spontaneous dull aching). In the scene, a bailiff was in the parlour to liquify assets (the touch on the irritated nerve). These descriptions will ring familiar to many patients today, but we have only recently discovered their neurobiological mechanisms. Understanding the mechanisms should help with the diagnosis and thus treatment of radiating pain symptoms that are present in most cases of cervical and lumbar radiculopathies, repetitive motion disorders, and complex regional pain syndromes, conditions that more often than not have no sign of nerve injury. Both sensory experiences alluded to in the quote can be explained by the effects of nerve inflammation, called neuritis. During neuritis, chemical and mechanical stimuli of the affected nerve lead to the generation of nociceptor action potentials (and pain). The presence of inflammation and constituent inflammatory mediators leads to tonic discharge,2Govea RM Barbe MF Bove GM Group IV nociceptors develop axonal chemical sensitivity during neuritis and following treatment of the sciatic nerve with vinblastine.J Neurophysiol. 2017; 118: 2103-2109Crossref PubMed Scopus (6) Google Scholar predicted to be perceived as a spontaneous dull ache. Mechanical stimulation of the inflamed nerve also leads to nociceptor discharge,3Bove GM Ransil BJ Lin HC Leem JG Inflammation induces ectopic mechanical sensitivity in axons of nociceptors innervating deep tissues.J Neurophysiol. 2003; 90: 1949-1955Crossref PubMed Scopus (104) Google Scholar predicted to be perceived as a touch on the irritated nerve. The common mechanism of these axonal changes appears to be the interference of axoplasmic transport, which is the mechanism by which sensory transductive channels are conveyed to the receptive terminals of neurons. During neuritis, the accumulation of these channels occurs on the axon, creating ectopic receptive fields.2Govea RM Barbe MF Bove GM Group IV nociceptors develop axonal chemical sensitivity during neuritis and following treatment of the sciatic nerve with vinblastine.J Neurophysiol. 2017; 118: 2103-2109Crossref PubMed Scopus (6) Google Scholar, 4Dilley A Richards N Pulman KG Bove GM Disruption of fast axonal transport in the rat induces behavioral changes consistent with neuropathic pain.J Pain. 2013; 14: 1437-1449Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 5Dilley A Bove GM Disruption of axoplasmic transport induces mechanical sensitivity in intact rat C-fibre nociceptor axons.J Physiol. 2008; 586: 593-604Crossref PubMed Scopus (39) Google Scholar Both perceptions would be felt distally to the inflamed site. These changes form the basis for some of our nerve-related clinical tests, such as the straight-leg raise. This test mechanically stimulates the sciatic nerve. Radiating pain evoked by the straight-leg raise is almost certainly due to axonal mechanical sensitivity. In these patients, palpating or tapping the nerve (Tinel's test) will cause radiating symptoms as well. Including focal neuritis as a diagnostic possibility could refine the treatment approaches for many patients with radiculopathies, repetitive motion disorders, and complex regional pain syndromes, and others who present with symptoms that are suspicious of nerve damage but who do not have definite findings upon routine examination. We declare no competing interests.

This Book is concise, superbly illustrated (print + electronic) textbook that brings together a reliable, clear and up to date guide to surface anatomy and its underlying gross anatomy, combined with a practical application of ultrasound and other imaging modalities.

Background Many patients with neuropathic pain present without signs of nerve injury on routine clinical examination. Some of these patients may have inflamed peripheral nerves (neuritis). In this study, we have examined whether neuritis causes changes within the dorsal horn that may contribute to a central pain mechanism. Comparisons have been made to a model of axonal transport disruption induced using vinblastine, since neuritis disrupts such processes. Results At the peak of cutaneous hypersensitivities, recordings from wide dynamic range neurons revealed increases in wind-up following neuritis but not vinblastine treatment. Ongoing activity from these neurons was unchanged. Vinblastine treatment caused a reduction in the responses of wide dynamic range neurons to noxious mechanical stimulation of the receptive field. The response of neurons to innocuous mechanical stimulation was also reduced in wide dynamic range neurons that were at a depth ≥550 µm following vinblastine treatment. An examination of the superficial dorsal horn revealed an increase in c-Fos–positive neurons in both groups following electrical stimulation of the sciatic nerve. The area of dorsal horn expressing substance P was also decreased following vinblastine treatment. Conclusion These findings indicate that a minor nerve insult, such as neuritis, can lead to changes within the dorsal horn that are consistent with a central neuropathic pain mechanism.