UNASSIGNED: The immune system is believed to be important in the initiation and maintenance of chronic pain.
UNASSIGNED: The aim was to investigate whether patients with chronic painful polyneuropathy (PP) differ in cytokine profiles of serum and/or cerebrospinal fluid (CSF) compared with pain-free controls.
UNASSIGNED: Thirty-nine patients (16 women and 23 men, mean age, 69.2 ± 12.7 years, range 41-92 years) with PP (mean duration 43 ± 48.3 months) were phenotyped with quantitative sensory testing and electroneurography, and serum and CSF samples were analyzed by 40-multiplexed, bead-based cytokine immunoassays. Results were compared with 36 age- and gender-matched patients with normal pressure hydrocephalus and absence of abnormal CSF findings.
UNASSIGNED: Compared with controls, patients with PP had lower concentrations of several proinflammatory and anti-inflammatory chemokines and cytokines in CSF, and others showed the same tendency, among these were tumor necrosis factor-α (14.1 ± 10.0 vs 23.9 ± 16.4 pg/mL, P < 0.005), interleukin (IL)-2 (0.6 ± 0.4 vs 1.2 ± 0.6 pg/mL, P < 0.0001), IL-6 (4.7 ± 6.8 vs 7.3 ± 9 pg/mL, P = 0.001), and IL-10 (7.5 ± 6.8 vs 16.8 ± 19.2 pg/mL, P < 0.01), whereas no differences were observed in serum.
UNASSIGNED: Results suggest that (1) inflammatory mediators play a minor role in the maintenance of chronic pain in contrast to initiation of acute pain, (2) chemokines/cytokines are downregulated in chronic pain, or (3) chemokines/cytokines have a protective role for nerve regeneration that is disturbed in patients with chronic pain.

Sensory features of autism include hypo- or hyper-reactivity to pain; however, previous studies on pain in autism lead to conflicting results. Here, we present the state of the art and the methodological challenges concerning pain perception in autism, focusing on studies that used standardized protocol as Quantitative Sensory Testing (QST) to measure perception. Despite there are still scant evidences found with the use of QST, they have challenged the presumed hyposensitivity to pain in autisms, which emerged from parents\' reports. Both, peripheral and central mechanisms, have been found involved in typical features of perception in autism. Nonetheless, evidences with controlled protocols are still scarce, and even scarcer are studies focused on children. Overall, complex ethical challenges have to be overcome in order to collect subjective and objective measures from autistic children. With heterogeneous neurodevelopmental features, or intellectual disability, novel or modified protocols are needed.

UNASSIGNED: In patients with sickle cell disease (SCD), negative physical and emotional experiences result from intense chronic and acute pain episodes, but factors underlying these, and their interactions, are not well understood. The arginine vasopressin receptor 1a gene (AVPR1A) single nucleotide polymorphism rs10877969 has been previously associated with aspects of acute pain and stress related pain. In this study, we tested for associations between this SNP, thermal and pressure pain thresholds, clinical pain, and stress in people with SCD.
UNASSIGNED: 150 adults enrolled with SCD completed pain intensity measures (Average Pain Intensity, API) and the Perceived Stress Questionnaire (PSQ). Thermal and pressure pain threshold data were available from quantitative sensory testing (QST), and rs10877969 genotypes were obtained.
UNASSIGNED: In models adjusted for age and gender, between rs10877969 genotypes, we observed no significant differences in thermal (cold, p = 0.66; heat, p = 0.91) and mechanical (pressure, p = 0.33) pain thresholds. The association of rs10877969 with API (p = 0.09) was borderline, but non-significant with PSQ (p = 0.51). The correlation between clinical pain and environmental stress was significant, r = 0.18, p = 0.024, however, the interaction of genotype and PSQ was not significant (p = 0.63).
UNASSIGNED: Clinical and experimental pain were not significantly associated with the rs10877969 genotype. The rs10877969 genotype did not moderate the correlation between environmental stress and clinical pain in this population. However, a trend toward a protective T allele effect on average pain rating in SCD warrants future exploration of this SNP/gene in SCD.

Mechanisms of complex regional pain syndrome (CRPS) are still debated. Identifying subgroups of patients have been attempted in the hope of linking clinical findings to possible mechanisms. The aim of the present study was to investigate whether subgroups of CRPS (based on quantitative sensory testing (QST)-results) differed with respect to different characteristics of pain like spontaneous ongoing or paroxysmal pain and mechanical dynamic allodynia.
61 CRPS-patients (type 1 and 2) were examined clinically and with QST, in affected and contralateral extremity, with assessment of thresholds for warmth, cold and heat-and cold pain.
43 patients (20 men, 23 men) were diagnosed with CRPS 1 (70.5%) and 18 patients (8 women and 10 men) with CRPS 2 (29.5%). Three subgroups were defined based on thermal thresholds; A (thermal allodynia 22.9%), B (thermal hyposensitivity 37.3%), C (thermal allodynia and hyposensitivity 39.3%). Paroxysmal pain was more prevalent in patients with thermal allodynia (merging group A + C, 25/38-65.8%) compared to patients without thermal allodynia (group B, 5/23-21.7%) (p-value=0.00085).
We suggest that cold allodynia is based on hyper-excitability of very superficial skin nociceptors. The correlation between paroxysmal pain, allodynia to light touch and cold allodynia suggests that activity in those peripheral nociceptors can drive both, paroxysmal pain and spinal sensitization leading to stroke evoked allodynia. Mechanistically, the physical cold stimulus can unmask disease-related hyperexcitability by closure of temperature-sensitive potassium channels or induction of resurgent currents. Small fiber degeneration alone may not be the crucial mechanism in CRPS, nor explain pain.

Aims: The aim of this study was to define the sensory phenotypes of taxane-induced peripheral neuropathy (TIPN) between neuropathic and nonneuropathic symptoms in a breast cancer population to identify future targets for mechanism-based pain management. Methods: Participants (n = 48) with stage I-III breast cancer. Self-report questionnaires and quantitative sensory testing were used to assess sensory symptoms. The self-report version of the Leeds Assessment for Neuropathic Symptoms and Signs (S-LANSS) divided the groups into neuropathic and nonneuropathic sensory phenotypes. In total, five visits over approximately 8 months assessed each participant from pre-chemotherapy to 6 months post-chemotherapy. Results: Out of 191 nerve assessments, 150 had an S-LANSS <12 defined as \"nonneuropathic\" and 41 scored >12, which was defined as \"neuropathic.\" Numeric Pain Rating Scale (NPRS) was analyzed based on percentages of those experiencing 1+ pain (graded 1/10 or higher) versus no pain. The neuropathic group had 82.9% of 1+ pain vs. 28.7% in the nonneuropathic group (odds ratio = 7.49; 95% confidence interval, 2.76-20.3; P = 0.001). The neuropathic group reported impaired function on the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire (P = 0.002). Heat pain threshold resulted in statistical differences for the left hand but not the right hand in the neuropathic group (P = 0.05). No other quantitative data on warm/cool or cold or vibration demonstrated sensory differences between the groups. Conclusions: Few differences in sensory profiles measured using quantitative sensory testing (QST) were found. Heat pain thresholds were normalized, possibly suggesting that the neuropathic group retained C-fiber and transient potential vanilloid 1 (TRPV1) function. Participants with neuropathic pain demonstrated significant differences with increased pain and decreased function.
Objectif: Déterminer les phénotypes sensoriels associés à la neuropathie périphérique induite par le taxane dans une population de personnes atteintes de cancer du sein, selon qu’elles présentent des symptômes de neuropathie ou non, afin de déterminer les cibles futures pour la prise en charge de la douleur axée sur les mécanismes.Méthodes: Participants (n = 48) atteints d’un cancer du sein de stade I-III. Des questionnaires d’auto-évaluation et des tests sensoriels quantitatifs ont été utilisés pour évaluer les symptômes sensoriels. À l’aide de la version d’auto-évaluation de l’outil d’évaluation des symptômes et des signes de la douleur neuropathique de Leeds (S-LANSS), les groupes ont été divisés en phénotypes sensoriels avec neuropathie et sans neuropathie. Au total, cinq visites échelonnées sur une période d’environ huit mois ont permis d’évaluer chaque participant avant le début de la chimiothérapie jusqu’à six mois après le début de celle-ci.Résultats: 191 évaluations des nerfs, parmi lesquelles 150 participantes ont obtenu une note < 12 pour le S-LANSS, définis comme «sans neuropathie », tandis que 41 participantes ont obtenu une note > 12, définie comme « avec neuropathie ». L’échelle numérique d’évaluation de la douleur a été analysée sur la base du pourcentage de participantes éprouvant une douleur égale ou supérieure à 1 (note de 1/10 ou plus) comparativement à aucune douleur. 82,9 % des patientes du groupe avec neuropathie éprouvaient une douleur égale ou supérieure à 1 comparativement à 28,7% pour le groupe sans neuropathie (RR = 7,49, CI 95 % 2,76-20,3, p = 0,001). Le groupe avec neuropathie a fait état d’une altération du fonctionnement selon le questionnaire DASH (p = 0,002). Des différences significatives ont été observées en ce qui concerne le seuil de la douleur thermique pour la main gauche, mais pas pour la main droite dans le groupe avec neuropathie (p = 0,05). Aucune autre donnée quantitative portant sur la sensibilité aux températures chaudes, tièdes ou froides, ou encore à la vibration, n’a révélé de différences sensorielles entre les groupes.Conclusions: On a constaté peu de différences entre les profils sensoriels mesurés par les tests sensoriels qualitatifs. Les seuils de douleur thermique ont été normalisés, ce qui indique probablement le maintien du fonctionnement des fibres de C et du TRPV1 chez le groupe avec neuropathie. Des différences significatives ont été observées chez les personnes souffrant de douleur neuropathique, dont une augmentation de la douleur et une diminution du fonctionnement.

Therapeutic advances in hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy extended life expectancy and delayed symptom progression especially in patients with early disease. Thus, detection and monitoring of asymptomatic carriers gained importance. However, there is still limited consensus on genetic screening of ATTRv-polyneuropathy patients\' family members and diagnostic tests that must be done in the follow-up. In this study, we followed prospectively five asymptomatic carriers of a family with ATTRV30M (p.Val50Met) mutation by different diagnostic tests for three years. The carriers were followed by neurological examination, nerve conduction studies, sympathetic skin response test, heart rate variability, SFN-SIQ and DN4 questionnaires, quantitative sensory testing (QST), skin biopsy and in vivo corneal confocal microscopy. Nerve conduction studies, sympathetic skin response test and heart rate variability were normal in all for three years. Baseline QST and SFN-SIQ were normal but became abnormal during follow-up of two individuals who developed small fiber neuropathy symptoms. Baseline intraepidermal nerve fiber density was low in three carriers and decreased to below normative values in all during follow-up, while corneal sub-basal nerve density was low in all carriers compared to controls during the entire follow-up. Thus, our study showed that SFN-SIQ and QST are useful diagnostic tools to detect the transition to symptomatic ATTRv-polyneuropathy.

BACKGROUND: Up to 25% of people who have had carpal tunnel release surgery (CTR) fail to report improvement; however, evidence for prognostic indicators in this surgical cohort is limited. To identify candidate prognostic factors, this study investigated the association of quantitative sensory testing (QST) derived sensory phenotype and attendant impairment with patient-reported surgical outcome.
METHODS: With ethical approval and informed consent, this prospective observational longitudinal study recruited patients from two London hospitals. Multimodal phenotyping measures including quantitative sensory testing (QST), pain parameters, insomnia, pain-related worry, mood and function, were evaluated prior to; and at 3- and 6-months post-surgery. Pain in median nerve distribution with electrophysiologically confirmed conduction delay and DN4 score ≥ 4 was defined as neuropathic. Primary outcome was patient-rated change at 6 months, dichotomised as poor outcome; \"worse\" or \"no change\" and good outcome; \"slightly better\", \"much better\" or \"completely cured\".
RESULTS: Seventy-six patients participated. Prior to surgery, substantial heterogeneity in established categories of somatosensory function was observed with 21% of participants categorised as having a healthy sensory phenotype; 29% with thermal hyperalgesia; 32% mechanical hyperalgesia and 18% sensory loss. Seventy six percent of participants were classified as having neuropathic pain, 33% with high levels of pain related worry and 64% with clinical insomnia. Observed differences in pain, sleep impairment, psychological factors and function, between sensory phenotypic groups, was not significant. At 3- and 6-months post-surgery there was significant improvement in all phenotyping measures with a moderate to large effect size. Thermal and mechanical measures of somatosensation improved (p < 0.001), as did functional ability (p < 0.001). Symptom severity diminished (p < 0.001), as did pain-related worry (p < 0.001), anxiety (p = 0.02) and insomnia (p < 0.001). Patient-rated surgical outcome was good in 92% of the cohort, poor in 8%. Baseline sensory phenotype category was not associated with surgical outcome however pain-related worry, anxiety and functional interference were significantly associated with outcome (p ≤ 0.05).
CONCLUSIONS: In patients undergoing carpal tunnel surgery, pain-related worry, anxiety and pain functional interference are candidate prognostic outcome factors and require further elucidation.

To prevent pain associated with 8% capsaicin application, pretreatment with local anesthetics, such as EMLA (eutectic mixture of lidocaine 2.5% and prilocaine 2.5%), is considered an option. However, there is contradicting evidence regarding the effects of local analgesia on capsaicin-induced desensitization. In session 1, 2 skin areas in each forearm of 24 healthy volunteers were randomized to 2-hour pretreatment with EMLA/placebo cream. After pretreatment, 8% capsaicin patches were applied for 3 hours in 1 placebo and 1 EMLA pretreated area, obtaining the following four areas: Capsaicin + EMLA, Capsaicin + Placebo, EMLA alone, and Placebo. Pain intensity scores were assessed during the 3-hour application of capsaicin. Warmth detection, heat pain sensitivity, and microvascular reactivity were measured after the removal of capsaicin. After 24 hours, in session 2, all tests were repeated followed by histamine application in each area to examine itch intensity and neurogenic flare. Overall, EMLA caused significant reductions in capsaicin-induced pain compared with placebo (P= .007) and enhanced the capsaicin-induced increase in superficial blood perfusion immediately after the 3-hour capsaicin application (P< .01). Regardless of pretreatment, capsaicin induced heat hyperalgesia immediately after the application (P< .001). Twenty-four hours post application, heat pain sensitivity was normalized. However, WDT increased significantly (P< .001). Capsaicin tended to reduce the itch intensity and significantly reduced the neurogenic flare (P< .05) induced by histamine compared with EMLA alone. The findings suggest that pretreatment with topical analgesic cream reduces application site pain without interfering with the 8% topical capsaicin-induced desensitization. PERSPECTIVE: Pretreatment with local anesthetic EMLA cream might be considered a good therapeutic option to reduce the pain associated with 8% capsaicin application currently used for treatment of neuropathic pain syndromes. This study also suggests the existence of a synergistic effect of capsaicin and EMLA on the process of neurogenic inflammation.

BACKGROUND: Spinal infections represent a therapeutic challenge. The often protracted course of the disease is accompanied by pain, which can lead to a chronic pain experience even after the infectious disease has been treated successfully. The aim of this study was to investigate possible risk factors of pain chronification.
METHODS: In a prospective study, 14 patients with spinal infections were examined at admission (T1), at discharge from inpatient therapy (T2), and three to eight months postoperatively (T3) byquestionnaires on risk factors for pain chronification and by quantitative sensory testing (QST).
RESULTS: In-patient treatment lasted on average 45.3 days (±33.13). The patients complained of pain for 3.43 months (±2.77) prior to inpatient treatment. The visual analogue scale (VAS) for pain (0-10) and the Oswestry Disability Index detected significant improvement in the course of the study. However, patients also reported catastrophic thinking, as well as fear of movement and (re)-injury.
CONCLUSIONS: In summary, our results demonstrate that patients with spinal infections did not suffer from pain chronification, but might benefit from an interdisciplinary therapeutic approach, which emphasizes promoting active pain-coping strategies, as well as addressing fear of movement and catastrophic thinking.

To study for the first-time, pain perception, pain sensitivity, and self-reported pain in young adults with long disease duration of juvenile idiopathic arthritis (JIA) compared with controls.
Children from Central Norway diagnosed with JIA between 1997 and 2004 were included consecutively in a population-based prospective study. Children with onset 1997-2000 were part of the Nordic JIA cohort. Controls were age- and sex-matched. In 2015-2017, study visits with investigator-blinded quantitative sensory testing (QST) comprising cold and warm detection thresholds (CDT/WDT), cold and heat pain thresholds (CPT/HPT), pressure pain threshold (PPT), and a suprathreshold heat pain test were performed. We constructed separate multilevel models for each variable of detection and pain thresholds with interaction between groups and site adjusted for the effect of age and sex.
Among 96 young adults with JIA, 71% were female, median age was 22.7 years, disease duration was 16.1 years, and 47% had oligoarticular disease. Among 109 controls, 71% were female, and median age was 23.5 years. Participants with JIA had lower pressure pain thresholds (PPTs) (95% CI) compared to controls, upper limb 888 (846,930) versus 1029 (999,1059) kPa and lower limb 702 (670,734) versus 760 (726,794) kPa. Participants with inactive disease had the lowest PPTs and cold pain thresholds (CPTs), compared to those in remission off medication and those with active disease. Minor differences were found regarding CDT/WDT and CPT/HPT in JIA compared to controls. The median (IQR) temperature needed to evoke pain = 6 on a 0-10 numeric rating scale (NRS) in the suprathreshold heat pain tests were lower in JIA than in controls (46 °C (45-47 °C) versus 47 °C (46-48 °C)). We found no associations between self-reported pain and pain thresholds.
Our results indicate for the first time that young adults with long disease duration of JIA may have altered pain perception and sensitivity compared to controls. A clinical implication may be the importance of early treatment to quickly achieve pain-free remission and avoid long-term pain sensitization.