Neuropathic-like Pain Research Articles

Validation of a questionnaire for Central nervous system Aspects of joint Pain: the CAP questionnaire.

Neuropathic-like pain, fatigue, cognitive difficulty, catastrophising, anxiety, sleep disturbance, depression, and widespread pain associate with a single factor in people with knee pain. We report the Central Aspects of Pain questionnaire (CAP) to characterise this across painful musculoskeletal conditions. CAP was derived from the 8 item CAP-Knee questionnaire, and completed by participants with joint pain in the Investigating Musculoskeletal Health and Wellbeing survey. Subgroups had osteoarthritis, back pain or fibromyalgia. Acceptability was evaluated by feedback and data missingness. Correlation coefficients informed widespread pain scoring threshold in relation to the other items, and evaluated associations with pain. Factor analysis assessed CAP structure. Intraclass Correlation Coefficient (ICC) between paper and electronic administration assessed reliability. Friedman test assessed score stability over 4 years in people reporting knee osteoarthritis. Data were from 3579 participants (58% female, median age; 71 years), including subgroups with osteoarthritis (n = 1158), back pain (n = 1292) or fibromyalgia (n = 177). Across the 3 subgroups, ≥10/26 painful sites on the manikin scored widespread pain. Reliability was high (ICC= 0.89 (95% CI: 0.84-0.92)) and CAP scores fit to 1 and 2 factor model, with a total CAP score that was associated with pain severity and quality (r = 0.50-0.72). In people with knee pain, CAP scores were stable over 4 years at the group level, but displayed significant temporal heterogeneity within individual participants. Central Aspects of Pain is reliably measured by the CAP questionnaire across a range of painful musculoskeletal conditions, and is a changeable state.

The Relationships Among Chronic Pain Subtypes, Motor Function, and Physical Activity in Community-Dwelling Japanese Older Adults: A Cross-Sectional Study.

We investigated the relationships among motor function, physical activity, and the characteristics of chronic pain (the number of pain sites, pain intensity, and pain-type). Cross-sectional study. An ongoing community-based prospective study conducted in Itoshima, Japan. Community-dwelling Japanese aged 65-75 years (n = 805; 401 men, 404 women). Chronic pain subtypes were examined in terms of the number of pain sites, pain intensity, and pain type. Motor function was evaluated by handgrip strength, walking speed, and the 5 Times Stand-up and Sit Test (FTSST). Locomotive activity, non-locomotive activity, and sedentary time were evaluated by a tri-axial accelerometer as physical-activity parameters. Multiple regression model adjusting for age, sex, education level, employment status, subjective economic status, body mass index, cognitive function, comorbidity, current tobacco use, current alcohol consumption, and regular exercise. In a multivariate analysis, the subjects' walking speed was negatively associated with multisite, moderate-to-severe, and neuropathic-like pain. The FTSST was positively associated with single-site, moderate-to-severe, and neuropathic-like pain. There was no significant association between handgrip strength and any chronic pain subtypes. Locomotive activity was negatively related to multisite, moderate-to-severe, and neuropathic-like pain, but there was no clear association between the amount of non-locomotive activity, sedentary time, and chronic pain subtypes. Severe chronic pain was associated with decreased locomotion-related motor function and physical activity.

Neuropathic post-COVID pain symptomatology is not associated with serological biomarkers at hospital admission and hospitalization treatment in COVID-19 survivors

ObjectiveEvidence suggests that individuals who had survived to coronavirus disease, 2019 (COVID-19) could develop neuropathic post-COVID pain. This study investigated the association of serological biomarkers and treatments received during hospitalization with development of neuropathic-associated symptoms.MethodsOne hundred and eighty-three (n = 183) previously hospitalized COVID-19 survivors during the first wave of the pandemic were assessed in a face-to-face interview 9.4 months after hospitalization. Nineteen serological biomarkers, hospitalization data, and treatment during hospitalization were obtained from medical records. Neuropathic pain symptoms (Self-Report Leeds Assessment of Neuropathic Scale), sleep quality (Pittsburgh Sleep Quality Index), pain catastrophizing (Pain Catastrophizing Scale) and anxiety/depressive levels (Hospital Anxiety and Depression Scale) were assessed.ResultsThe prevalence of post-COVID pain was 40.9% (n = 75). Fifteen (20%) patients reported neuropathic symptoms. Overall, no differences in hospitalization data and serological biomarkers were identified according to the presence or not of neuropathic-associated symptoms. Patients with post-COVID pain had the highest neutrophil count, and post hoc analysis revealed that patients with neuropathic post-COVID associated symptoms had lower neutrophil count (p = 0.04) compared with those without neuropathic pain, but differences were small and possible not clinically relevant. No differences in fatigue, dyspnea, brain fog, anxiety or depressive levels, poor sleep, or pain catastrophism between patients with and without neuropathic symptoms were found.ConclusionIt seems that neuropathic-like post-COVID pain symptoms are not associated with neither of assessed serological biomarkers at hospital admission nor hospitalization treatments received in this cohort of hospitalized COVID-19 survivors.

Three dimensions of pain in osteoarthritis: development and validation of the Osteoarthritis Symptom Inventory Scale (OASIS).

We describe here the development and validation of the Osteoarthritis Symptom Inventory Scale (OASIS), a new self-administered questionnaire specifically designed to evaluate the various osteoarthritis (OA) pain symptoms with different dimensions related to OA pain mechanisms. The initial development phase and qualitative study generated a list of 17 descriptors reflecting OA pain and other associated symptoms, leading to the first version of the questionnaire (OASIS17). Each item was quantified on a 0-10 numerical scale. Validation was performed using 123 consecutive patients with OA pain recruited at 28 centers in France, mainly general practitioner offices. Validation involved: (i) determining the questionnaire's factorial structure through exploratory and confirmatory analyses, (ii) analyzing convergent and divergent validities (i.e., construct validity), (iii) assessing each item's test-retest reliability, and (iv) evaluating OASIS's ability to detect treatment effects (i.e., sensitivity to change). The final OASIS version includes nine items discriminating and quantifying three distinct, clinically relevant OA pain dimensions sensitive to treatment. OASIS9's psychometric properties suggest that it could improve the characterization of OA pain profiles for three clinically relevant domains: localized, neuropathic-like, and deep pain. The OASIS9 questionnaire could be used to phenotype OA pain patients and identify responders to various therapeutic interventions as a function of OA pain dimensions.

Neuropathic pain component and its association with time elapsed since pain onset in patients with low back pain.

Time elapsed since pain onset might affect the likelihood of neuropathic component in low back pain. The aim of this study was to investigate the relationship between neuropathic pain component and pain duration in patients with low back pain and to identify factors associated with neuropathic pain component. Patients with low back pain who received treatment at our clinic were enrolled. Neuropathic component was assessed using the painDETECT questionnaire at the initial visit. PainDETECT scores and the results for each item were compared according to pain duration category (< 3months, 3months to 1year, 1year to 3 years, 3 years to 10 years, and ≥ 10 years). A multivariate analysis was used to identify factors associated with neuropathic pain component (painDETECT score ≥ 13) in low back pain. A total of 1957 patients, including 255 patients who reported neuropathic-like pain symptoms (13.0%), fully satisfied the study criteria for analysis. No significant correlation between painDETECT score and pain duration was observed (ρ=-0.025, p=0.272), and there were no significant differences between median painDETECT score or trend of change in the proportion of patients with neuropathic component and the pain duration category (p=0.307, p=0.427, respectively). The electric shock-like pain symptom was frequently reported in patients with acute low back pain, and the persistent pain pattern with slight fluctuations was predominant in chronic low back pain. The pattern of attacks with pain between them was much less common in patients with pain for 10 years or longer. Multivariate analysis revealed that a history of lumbar surgery, severe maximum pain, opioid use, lumbosacral radiculopathy, and sleep disturbance were significantly associated with a neuropathic component in low back pain. Time elapsed since current pain onset did not correlate with neuropathic pain component in patients with low back pain. Therefore, diagnostic and therapeutic approaches for this condition should be based on a multidimensional evaluation at assessment and not on pain duration alone.

Neuropathic-like Pain Symptoms and Their Association with Muscle Strength in Patients with Chronic Musculoskeletal Pain.

The relationship between sarcopenia and pain remains unclear; thus, this study evaluated whether muscle strength is independently associated with neuropathic-like pain symptoms in patients with chronic musculoskeletal pain. A cut-off score of painDETECT ≥13 was used to indicate a possible neuropathic component. Handgrip strength was measured, and muscle mass was estimated. A total of 2599 patients, including 439 patients who reported neuropathic-like pain symptoms (16.9%), were included for analysis. Handgrip strength was significantly lower in patients experiencing neuropathic-like pain symptoms (23.23 ± 10.57 vs. 24.82 ± 10.43 kg, p < 0.001), and this result was chiefly found in female patients. However, there was no difference in estimated muscle mass. Shorter duration of pain, opioid usage, pain in lower limbs, sleep disturbance, and lower handgrip strength were significantly associated with neuropathic-like pain symptoms. In patients with handgrip strength below the reference values by sex, experiencing radiating pain and at least moderate sensory symptoms by light touch and thermal stimulation were more frequently reported. In conclusion, lower handgrip strength appeared to be an independent factor associated with symptoms suggestive of neuropathic pain in this population. Interventional studies are required to determine whether improvement in muscle strength can reduce the neuropathic pain component in chronic musculoskeletal pain.

Neuropathic-like pain symptoms in inflammatory hand osteoarthritis lower quality of life and may not decrease under prednisolone treatment.

BackgroundPain is common in hand osteoarthritis (OA) and multiple types may occur. We investigated the prevalence, associated patient characteristics, influence on health‐related quality of life (HR‐QoL) and response to anti‐inflammatory treatment of neuropathic‐like pain in inflammatory hand OA.MethodsData were analysed from a 6‐week, randomized, double‐blind, placebo‐controlled trial investigating prednisolone treatment in 92 patients with painful inflammatory hand OA. Neuropathic‐like pain was measured with the painDETECT questionnaire. Associations between baseline characteristics and baseline neuropathic‐like pain were analysed with ordinal logistic regression, association of baseline neuropathic‐like pain symptoms with baseline HR‐QoL with linear regression, painDETECT and visual analogue scale (VAS) change from baseline to week 6 and interaction of painDETECT with prednisolone efficacy on VAS pain change from baseline to week 6 with generalized estimating equations (GEE).ResultsOf 91 patients (79% female, mean age 64) with complete painDETECT data at baseline, 53% were unlikely to have neuropathic‐like pain, 31% were indeterminate and 16% were likely to have neuropathic‐like pain. Neuropathic‐like pain was associated with female sex, less radiographic damage and more comorbidities. Patients with neuropathic‐like pain had lower HR‐QoL (PCS‐6.5 [95% CI −10.4 to −2.6]) than those without. Neuropathic‐like pain symptoms remained under prednisolone treatment and no interaction was seen between painDETECT and prednisolone efficacy on VAS pain.ConclusionsIn this study, 16% of inflammatory hand OA patients had neuropathic‐like pain. They were more often female, had more comorbidities and had lower QoL than those without. Neuropathic‐like pain symptoms remained despite prednisolone treatment and did not seem to affect the outcome of prednisolone treatment.SignificancePain is the dominant symptom in hand OA, with an unclear aetiology. In this study, we found that neuropathic‐like pain may play a role in hand OA, that it showed associations with female sex, younger age and more comorbidities and that it lowered health‐related quality of life in hand OA. Neuropathic‐like pain in hand OA seems resistant to prednisolone therapy but did not seem to interfere with the treatment of inflammatory pain with prednisolone.

Neuropathic-like Pain in Fibrous Dysplasia/McCune-Albright Syndrome.

Pain is a major symptom in adults with fibrous dysplasia/McCune-Albright syndrome (FD/MAS) and response to current treatments, including bisphosphonates and standard analgesics (nonsteroidal anti-inflammatory drugs and opiates) is unpredictable. No studies have explored whether the type of pain is variable in this patient group. To determine the frequency of neuropathic-like pain in patients with FD/MAS. Retrospective, dual registry study. Community. FD/MAS online registries: the US-based Familial Dysautonomia Foundation (FDF) and the UK-based Rare and Undiagnosed Diseases (RUDY) study. Subjects completed questionnaires to evaluate the presence of features of neuropathic-like pain (painDETECT) and the impact on sleep quality (Pittsburgh Sleep Quality Index) and mental health (Hospital Anxiety and Depression Scale). Descriptive statistics were used to characterize the prevalence and associated burden of neuropathic-like pain. Incidence of neuropathic, nociceptive, and unclear pain. Of 249 participants, one third experienced neuropathic-like pain. This group had statistically significantly (P < 0.001) worse mental well-being and sleep in comparison to those with predominately nociceptive pain. Neuropathic-like pain is common in patients with FD/MAS and associated with worse quality of life. Evaluation of pain in patients with FD/MAS should include assessment of neuropathic-like pain to guide personalized approaches to treatment and inform future research.

Joint Damage and Neuropathic Pain in Rats Treated With Lysophosphatidic Acid.

Joint pain is a complex phenomenon that involves multiple endogenous mediators and pathophysiological events. In addition to nociceptive and inflammatory pain, some patients report neuropathic-like pain symptoms. Examination of arthritic joints from humans and preclinical animal models have revealed axonal damage which is likely the source of the neuropathic pain. The mediators responsible for joint peripheral neuropathy are obscure, but lysophosphatidic acid (LPA) has emerged as a leading candidate target. In the present study, male and female Wistar rats received an intra-articular injection of LPA into the right knee and allowed to recover for 28 days. Joint pain was measured by von Frey hair algesiometry, while joint pathology was determined by scoring of histological sections. Both male and female rats showed comparable degenerative changes to the LPA-treated knee including chondrocyte death, focal bone erosion, and synovitis. Mechanical withdrawal thresholds decreased by 20-30% indicative of secondary allodynia in the affected limb; however, there was no significant difference in pain sensitivity between the sexes. Treatment of LPA animals with the neuropathic pain drug amitriptyline reduced joint pain for over 2 hours with no sex differences being observed. In summary, intra-articular injection of LPA causes joint degeneration and neuropathic pain thereby mimicking some of the characteristics of neuropathic osteoarthritis.

Different genes may be involved in distal and local sensitization: A genome-wide gene-based association study and meta-analysis.

BackgroundNeuropathic pain symptoms and signs of increased pain sensitization in osteoarthritis (OA) patients may explain persistent pain after total joint replacement (TJR). Therefore, identifying genetic markers associated with pain sensitization and neuropathic‐like pain phenotypes could be clinically important in identifying targets for early intervention.MethodsWe performed a genome‐wide gene‐based association study (GWGAS) using pressure pain detection thresholds (PPTs) from distal pain‐free sites (anterior tibia), a measure of distal sensitization, and from proximal pain‐affected sites (lateral joint line), a measure of local sensitization, in 320 knee OA participants from the Knee Pain and related health in the Community (KPIC) cohort. We next performed gene‐based fixed‐effects meta‐analysis of PPTs and a neuropathic‐like pain phenotype using genome‐wide association study (GWAS) data from KPIC and from an independent cohort of 613 post‐TJR participants, respectively.ResultsThe most significant genes associated with distal and local sensitization were OR5B3 and BRDT, respectively. We also found previously identified neuropathic pain‐associated genes—KCNA1, MTOR, ADORA1 and SCN3B—associated with PPT at the anterior tibia and an inflammatory pain gene—PTAFR—associated with PPT at the lateral joint line. Meta‐analysis results of anterior tibia and neuropathic‐like pain phenotypes revealed genes associated with bone morphogenesis, neuro‐inflammation, obesity, type 2 diabetes, cardiovascular disease and cognitive function.ConclusionsOverall, our results suggest that different biological processes might be involved in distal and local sensitization, and common genetic mechanisms might be implicated in distal sensitization and neuropathic‐like pain. Future studies are needed to replicate these findings.SignificanceTo the best of our knowledge, this is the first GWAS for pain sensitization and the first gene‐based meta‐analysis of pain sensitization and neuropathic‐like pain. Higher pain sensitization and neuropathic pain symptoms are associated with persistent pain after surgery hence, identifying genetic biomarkers and molecular pathways associated with these traits is clinically relevant.

Persistent, neuropathic-like trigeminal pain after dental implant loading.

BackgroundPainful post-traumatic trigeminal neuropathy (PTTN) is a known complication of dental implant therapy. Besides cases resulting of nerve damage during surgery or implant placement, some patients report delayed neuropathic-like symptoms only after implant loading i.e. crown placement. The present retrospective study aimed at describing the clinical features of pain experienced by these patients. Material and MethodsThe cohort of patients consulting for chronic orofacial pain at the Groupe Hospitalier Pitié-Salpêtrière (Paris, France) between 2015 and 2020 (ABCD study, IRB # TPS 1106180), was screened for patients with history of dental implant placement and persistent pain. Patients with no pain after surgery for 6 months and pain resulting from the loading of the implant, were included. ResultsAmong 675 files of patients screened, 5 fulfilled inclusion criteria. All patients were women, mean age 62.4 ± 9.8 y.o, and reported trigeminal neuropathic-like persistent pain. Intensity of pain was described as moderate to severe, with pin and needles, burning and tingling, and electric shocks as main symptoms. ConclusionsThese results suggest that implant loading can trigger trigeminal neuropathy, in a previously sensitized nerve. Putative neurophysiological basis of the phenomenon is discussed. Key words:Neuropathic pain, trigeminal nerve, lesion, dental implant, implant loading, allodynia.

P093 Algodystrophy in children: a case report

Abstract Background Algodystrophy is an entity very often unrecognized by pediatricians. The evolution is readily dragging and disabling in the absence of early and coordinated care. The Objective: Based on a case observed in a 10-year-old boy, the authors recall the main characteristics of the syndrome, guiding the practitioner to make the diagnosis, and implement appropriate and early therapy. Observation A 10-year-old boy with no previous medical history, presenting with neuropathic-like pain in the wrist and the hand that started a month ago without any triggers. Clinical exam noted functional impotence, a whole limb tremor, hyperesthesia as well as allodynia. The patient's hand is swollen and warm with a claw-like appearance. The rest of the body exam is normal. The laboratory markers and x-rays of the whole limb are normal. Bone scintigraphy confirms the diagnosis of wrist algodystrophy. The treatment combining corticosteroids, functional rehabilitation, and psychotherapy allowed a favorable outcome with no sequelae. Conclusion The diagnosis of algodystrophy remains too often unrecognized, and its management is sometimes inadequate. Early diagnosis and treatment improve the prognosis.

Effect of preoperative duloxetine treatment on postoperative chronic residual pain after total hip or knee arthroplasty: a randomised controlled trial

ObjectivesA key predictor for developing chronic residual pain after total knee or hip arthroplasty (TKA/THA) is sensitisation. Sensitisation can be defined as an ‘increased responsiveness of nociceptive neurons in the...

Low prevalence of neuropathic-like pain symptoms in long-term controlled acromegaly

PurposePain is a common symptom of acromegaly, impairing health-related quality of life (HR-QoL) significantly despite long-term disease remission. Neuropathic-like pain (NP-like) symptoms are invalidating, with great impact on HR-QoL. Studies characterizing or investigating the etiology of pain in acromegaly are scarce. Therefore, we aimed to assess NP-like symptoms in a cohort of controlled acromegaly patients.MethodsForty-four long-term controlled acromegaly patients (aged 62.6 ± 12.6 years; 56.8% female) were included in this cross-sectional study. NP-like symptoms were assessed using the validated painDETECT questionnaire. Patients were divided in three probability-based NP-like symptoms categories based on the total score (range 0–35): unlikely (≤ 12), indeterminate (13–18) and likely (≥ 19). HR-QoL (physical component score (PCS), and mental component score (MCS)), and self-reported pain were assessed using Short Form-36 (SF-36). Potential risk factors were determined using linear regression analyses.ResultsSelf-reported pain was reported by 35 patients (79.5%). Likely NP-like symptoms were present in 4/44 patients (9.1%), and indeterminate NP-like symptoms in 6/44 patients (13.6%). All patients with likely NP-like symptoms were female. Higher painDETECT scores were negatively associated with HR-QoL (PCS: r = − 0.46, P = 0.003; MCS: r = − 0.37, P = 0.018), and SF-36 pain scores (r = − 0.63, P < 0.0001). Female sex was a risk factor for NP-like symptoms.ConclusionsPain was prevalent in controlled acromegaly patients, whereas NP-like symptoms were relatively infrequent, and only observed in females. NP-like symptoms were associated with lower HR-QoL in acromegaly. Since specific analgesic therapy is available, awareness for characterization, increased understanding, and clinical trials regarding neuropathic pain identification and treatment in acromegaly patients are warranted.

Extradigital Glomus Tumor of the Forearm Identified During Neuromuscular Ultrasound: A Case Report

Glomus tumors are rare benign soft tissue tumors that arise from the glomus body. They typically develop in the subungual region but may develop extradigitally anywhere, in the upper or lower limbs. Extradigital glomus tumors can be misdiagnosed for years because of their atypical position and presentation. Being aware of an extradigital glomus tumor is important because they can be encountered during imaging studies and may be the cause of the patient’s symptoms. This report presents a case of an extradigital glomus tumor, of the forearm, diagnosed during neuromuscular sonography, in a patient with chronic intractable neuropathic-like pain, along the medial side of the left forearm. Sonographic imaging of the nerves, muscles, and tendons did not reveal any abnormalities. However, meticulous imaging of all tissue layers detected a subcutaneous vascular nodule. Subsequent excision biopsy and histopathologic assessment revealed a glomus tumor. After surgery, the patient experienced dramatic relief of pain. This case report highlights the importance of careful sonographic examination of all the tissues, including skin and subcutaneous tissue layers, to avoid missing non-neuromuscular pathologies that impact patient’s management.

COVID-19 Related Acro-Ischemic Neuropathic-like Painful Lesions in Pediatric Patients: A Case Series.

BackgroundA variety of skin manifestations have been associated with COVID-19 infection. Acral lesions on hands and feet, closely resembling chilblains, have been reported in association with COVID-19, which are nonspecific. These acro-ischemic painful lesions have been described mainly in asymptomatic and mildly symptomatic pediatric COVID-19 positive patients, without a precise pathogenetic mechanism. COVID-19-induced chilblains may portend an indolent course and a good outcome. In young patients, the IFN-1 response induces microangiopathic changes and produces a chilblain lupus erythematosus-like eruption with vasculitic neuropathic pain features.ObjectivesThis paper presented a case series of pediatric patients with COVID-19-related skin lesions and neuropathic-like pain.MethodsClinical outcomes were collected from 11 patients diagnosed with painful erythematous skin lesions with neuropathic-like pain and positive IgG for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).ResultsIt is a mildly symptomatic condition not related to severe pain rates, and it is treated with paracetamol due to the transitory nature of the problem, which provides good results.ConclusionsA particular point of interest is skin lesion manifestation as a further indirect sign of SARS-CoV-2 infection. Due to the initial manifestation of chilblains in pauci-symptomatic pediatric patients, they need to be immediately tested and isolated. Chilblains can be considered a clinical clue to suspect SARS-CoV-2 infection and help in early diagnosis, patient triage, and infection control.

Associations of peripheral and central pain mechanisms with voluntary muscle strength in people with knee pain

Purpose: Knee pain is a major cause of disability and approximately 25% of people, aged 55 years and over in the UK, experience knee pain. Pain might be caused by local structural changes or inflammation linked to knee osteoarthritis (OA), and might be associated with alterations in central nervous system pain processing. People with knee pain commonly report weakness or giving way of their knees, despite often a lack of evidence of structural instability. Knee pain can reduce quadriceps voluntary contractions, a process referred to as reflex inhibition. "Central mechanisms trait" (CMT), a composite self-report tool, was designed to measure central pain augmentation in individuals with knee pain (Akin-Akinyosoye et al. Osteoarthritis Cartilage 2020; 28(2):173-81). It can be measured using 8 questionnaire items addressing anxiety, depression, catastrophizing, neuropathic-like pain, fatigue, sleep disturbance, pain distribution, and cognitive impact. This study aimed to explore possible effects of central and peripheral pain mechanisms on muscle strength in people with knee pain. Methods: This is a sub-study embedded in the Nottingham Knee Pain and Health in the Community (KPIC) cohort study in the East Midlands region of the UK including 9506 men and women aged ≥ 40 years at baseline. 322 participants that reported knee pain took part in additional baseline clinical assessments and were invited for repeat assessment at 1 year. The “Early Knee Pain” group at baseline was defined as pain commencing within the past 3 years, with the “Established Knee Pain” group being those reporting moderate to severe knee pain that lasted more than 3 years. Clinical assessment related to central pain mechanisms comprised CMT and pressure pain detection thresholds (PPT) at the proximal tibia ipsilateral to the index knee. Assessment related to peripheral pain mechanisms were total radiographic OA score (Nottingham Line Drawing Atlas), and ultrasound synovitis score. The mean value of 3 repeats of maximum quadriceps voluntary contraction (MVC) for index knee was assessed by ‘Nicholas Manual Muscle Tester’ (Lafayette Instruments, Indiana). The index knee was selected based on the only (unilateral) or most painful knee (bilateral). A knee was randomly selected if all scores were the same. The index knee was the only knee that was analysed in this study. The dominant hand grip strength was measured by the mean value of 3 repeats using a JAMAR hydraulic dynamometer (Lafayette, Indiana). Associations were explored using Spearman’s correlation coefficient and multiple linear regression models. Results were presented with standardized coefficients beta (β value), 95% Confidence Interval (CI), and p-value. Results: Of the 322 participants that provided baseline data, 219 had early and 103 had established knee pain. Quadriceps and hand grip strength were each associated with knee pain severity both at baseline and in longitudinal analyses. In cross-sectional analyses at baseline, PPT and CMT were associated with quadriceps strength, more strongly than were radiographic OA scores, while ultrasound synovitis score was not significantly associated with muscle strength. CMT was associated with hand grip strength. At 1 year, 255 people were reassessed (181 with early knee pain and 74 with established knee pain). The correlations between baseline variables and year 1 quadriceps strength were examined for baseline index knee pain (r=-0.32, p<0.001), age (r= -0.08, p=0.2), female sex (r=-0.46, p<0.001), study group (r= -0.25, p<0.001), CMT (r=-0.44, p<0.001), PPT (r=0.29, p<0.001), global X-ray score (r=-0.13, p=0.001) and total ultrasound score (r=-0.01, p=0.9). In longitudinal regression analysis (after adjustment for the above variables plus baseline quadriceps strength) baseline CMT was associated with year 1 quadriceps strength (β=-0.20 (95%CI:-0.34 to -0.06); p=0.005; Table 1). Baseline CMT was also associated with year 1 hand grip strength (Table 1). Conclusions: Central mechanisms of pain are associated with reduced muscle strength, both at the index knee and at a distant site (hand). Central pain mechanisms appeared to drive these associations, whereas local radiographic changes did not appear to be strongly linked. Addressing central pain augmentation has potential to improve muscle strength and reduce frailty in people with knee pain.Tabled 1Baseline and longitudinal regression analyses for muscle strengthAnalysesDependent variableIndependent variablesBeta95% CIpBaseline regressionBaseline quadriceps strengthCMT-0.19-0.33 to -0.040.012PPT0.130.01 to 0.250.037Global X-ray-0.11-0.24 to 0.020.102Total ultrasound score0.03-0.10 to 0.160.645Baseline hand grip strengthCMT-0.21-0.33 to -0.080.001PPT0.190.08 to 0.300.001Longitudinal regressionYear 1 quadriceps strengthCMT-0.20-0.34 to -0.060.005PPT0.04-0.07 to 0.150.485Global X-ray0.01-0.12 to 0.140.831Total ultrasound score-0.03-0.15 to 0.090.637Year 1 hand grip strengthCMT-0.24-0.40 to -0.080.004PPT0.04-0.07 to 0.160.454 Open table in a new tab

Systematic review and meta-analsyis of the prevalence of neuropathic-like pain and/or pain sensitisation in people with knee and hip osteoarthritis

Purpose: Pain in osteoarthritis (OA) may be nociceptive or neuropathic-like in nature. In knee OA, pain severity is known to be poorly correlated with joint damage. Identifying a patient’s pain profile may guide the provision of specific therapy. This study aimed to determine the prevalence of neuropathic-like pain and/or pain sensitisation in people with knee and hip osteoarthritis, as defined by self-report questionnaires. The secondary aim was to determine whether prevalence differed according to patient setting.

The Central Aspects of Pain in the Knee (CAP-Knee) questionnaire; a mixed-methods study of a self-report instrument for assessing central mechanisms in people with knee pain

SummaryObjectivesPain is the prevailing symptom of knee osteoarthritis. Central sensitisation creates discordance between pain and joint pathology. We previously reported a Central Pain Mechanisms trait derived from eight discrete characteristics: Neuropathic-like pain, Fatigue, Cognitive-impact, Catastrophising, Anxiety, Sleep disturbance, Depression, and Pain distribution. We here validate and show that an 8-item questionnaire, Central Aspects of Pain in the Knee (CAP-Knee) is associated both with sensory- and affective- components of knee pain severity.MethodsParticipants with knee pain were recruited from the Investigating Musculoskeletal Health and Wellbeing study in the East Midlands, UK. CAP-Knee items were refined following cognitive interviews. Psychometric properties were assessed in 250 participants using Rasch-, and factor-analysis, and Cronbach's alpha. Intra-class correlation coefficients tested repeatability. Associations between CAP-Knee and McGill Pain questionnaire pain severity scores were assessed using linear regression.ResultsCAP-Knee targeted the knee pain sample well. Cognitive interviews indicated that participants interpreted CAP-Knee items in diverse ways, which aligned to their intended meanings. Fit to the Rasch model was optimised by rescoring each item, producing a summated score from 0 to 16. Internal consistency was acceptable (Cronbach's alpha = 0.74) and test–retest reliability was excellent (ICC2,1 = 0.91). Each CAP-Knee item contributed uniquely to one discrete ‘Central Mechanisms trait’ factor. High CAP-Knee scores associated with worse overall knee pain intensity, and with each of sensory- and affective- McGill Pain Questionnaire scores.ConclusionCAP-Knee is a simple and valid self-report questionnaire, which measures a single ‘Central Mechanisms’ trait, and may help identify and target centrally-acting treatments aiming to reduce the burden of knee pain.

Demise of nociceptive Schwann cells causes nerve retraction and pain hyperalgesia.

Recent findings indicate that nociceptive nerves are not "free", but similar to touch and pressure sensitive nerves, terminate in an end-organ in mice. This sensory structure consists of the nociceptive nerves and specialized nociceptive Schwann cells forming a mesh-like organ in subepidermis with pain transduction initiated at both these cellular constituents. The intimate relation of nociceptive nerves with nociceptive Schwann cells in mice raises the question whether defects in nociceptive Schwann cells can by itself contribute to pain hyperalgesia, nerve retraction, and peripheral neuropathy. We therefore examined the existence of nociceptive Schwann cells in human skin and their possible contribution to neuropathy and pain hyperalgesia in mouse models. Similar to mouse, human skin contains SOX10+/S100B+/AQP1+ Schwann cells in the subepidermal border that have extensive processes, which are intimately associated with nociceptive nerves projecting into epidermis. The ablation of nociceptive Schwann cells in mice resulted in nerve retraction and mechanical, cold, and heat hyperalgesia. Conversely, ablating the nociceptive nerves led to a retraction of epidermal Schwann cell processes, changes in nociceptive Schwann cell soma morphology, heat analgesia, and mechanical hyperalgesia. Our results provide evidence for a nociceptive sensory end-organ in the human skin and using animal models highlight the interdependence of the nerve and the nociceptive Schwann cell. Finally, we show that demise of nociceptive Schwann cells is sufficient to cause neuropathic-like pain in the mouse.