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Background: Changes in quantitative sensory testing (QST) parameters following topical anaesthesia could contribute to better elucidate underlying mechanisms of somatosensory alterations in temporomandibular disorder (TMD) pain patients. This placebo‐controlled crossover investigation compared the somatosensory profile following topical anaesthesia between TMD patients (n = 20) and healthy participants (n = 20). Methods: Cold detection threshold, warm detection threshold, cold pain threshold, heat pain threshold, mechanical detection threshold, mechanical pain threshold, wind‐up ratio and pressure pain threshold were assessed on the skin overlying the masseter at three consecutive days (baseline and immediately after lidocaine 4%/placebo cream). Mixed ANOVA and a coding system that accounts for the diversity of types of peripheral axons associated with the somatosensory parameters were applied for data analysis. Results: The lidocaine application caused no changes in the somatosensory sensitivity in the masseter region in TMD patients (P >.050), but sensitivity to cold, cold pain, touch and pinprick stimuli were reduced after topical anaesthesia in healthy participants (P <.050). Also, the degree of topical anaesthesia was greater in healthy participants (P =.008). The coding system suggested that TMD patients presented only Aδ‐fibre block, whereas a combination of either Aβ‐ and/or C‐fibre block was observed in 35% of healthy participants in addition to Aδ‐fibre block following lidocaine application. Conclusion: Quantitative sensory testing can be successfully applied to identify meaningful differences in the degree of hypoalgesia and hypoesthesia following short‐time topical anaesthesia. [ABSTRACT FROM AUTHOR]

BACKGROUND: One-third of individuals with acute low back pain (LBP) experience recurrent symptoms within 12 months but the underlying mechanisms are unclear. One explanation is that individuals experiencing recurrent LBP develop altered central pain processing that predisposes to symptom recurrence. We compared central pain processing between individuals experiencing their first episode of acute LBP, recurrent acute LBP, and pain-free controls. METHODS: A cross-sectional study was conducted to evaluate central pain processing in 11 individuals experiencing their first episode of acute LBP, 11 individuals with recurrent acute LBP, and 11 pain-free controls. Outcome measures included pain and disability, pressure and heat pain thresholds (PPTs and HPTs), nociceptive flexor withdraw reflex (NFR) and conditioned pain modulation (CPM). RESULTS: The NFR latency was shorter in individuals experiencing their first episode of acute LBP when compared with pain-free controls (p = 0.01). Descending inhibitory pain control measured by CPM was less efficient in both acute LBP groups when compared with pain-free controls. HPTs and PPTs did not differ between people with and without acute LBP. There were no differences between the two LBP groups for any outcome measure. CONCLUSIONS: These data demonstrate altered central pain processing in the acute stage of LBP. However, the degree of impairment did not differ between individuals with a first episode vs. recurrent acute LBP. These findings suggest that altered central pain processing in acute LBP is not related to a previous history of LBP. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this single-subject experimental study was to describe the patient's outcome following pain neuroscience education in combination with therapeutic exercise for Brazilian women with central sensitisation and a low level of education. Methods: Eight Brazilian women with central sensitisation and a low level of education were screened from a total of 57 patients with musculoskeletal disorders in an outpatient physiotherapy department. Twelve sessions were performed, once a week, including group pain education and supervised exercises. The outcome measures of pain intensity, functionality, catastrophizing, kinesiophobia, quality of life, knowledge of pain physiology and global improvement rating were collected pre- and post-intervention. Results: There was an improvement in pain (before median = 8.5, after median = 5.0; Z = −2.032, p =.042) and functionality (before median = 2.5, after median = 5.6; Z = −2.366, p =.018) at post-intervention evaluation measured by the Wilcoxon signed-rank test. A meaningful improvement was observed in global perceived effect. There were no statistically significant differences for other outcomes. Conclusion: Following a combination of pain neuroscience education with therapeutic exercise, Brazilian women with central sensitisation and a low level of education showed pain relief and improved function. Nonetheless, psychosocial factors, knowledge of pain and quality of life did not improve with the intervention. [ABSTRACT FROM AUTHOR]

The common chronic pain syndromes of fibromyalgia, regional pain syndrome, and complex regional pain syndrome have been made to appear separate because they have been historically described by different groups and with different criteria, but they are really phenotypically accented expressions of the same processes triggered by emotional distress and filtered or modified by genetics, psychology, and local physical factors.

Purpose: To translate and cross-culturally adapt the English version of the Central Sensitisation Inventory (CSI) into Thai (CSI-Thai) and to evaluate its psychometric properties in individuals with chronic non-specific neck pain., Materials and Methods: Cross-cultural translation and adaptation of the CSI were performed according to standard guidelines. A total of 340 participants were invited to complete the CSI-Thai, Visual Analogue Scale (pain intensity), Neck Disability Index, Fear-Avoidance Beliefs Questionnaire, Pain Catastrophising Scale (PCS), and Short Form-36. Psychometric evaluation included confirmatory factor analysis, internal consistency, test-retest reliability, agreement, and construct validity., Results: Dimensionality analyses indicated that a bifactor model, comprising one general factor plus four orthogonal factors, fit the CSI structure better than unidimensional and the four-factor models. The general factor showed substantial reliability (Cronbach α  = 0.91, Omega ω  = 0.94, and omega hierarchical ω - h  = 0.91). The intraclass correlation coefficient was 0.90, representing excellent stability over a 48 h interval. Moderate-to-strong correlations and acceptable-to-excellent discriminations were found between the CSI-Thai and all questionnaires. The exception was the PCS (no correlation and discrimination). The standard error of measurement and minimal detectable change of the CSI-Thai were 2.33 and 6.47, respectively., Conclusions: The translation and cross-cultural adaptation of the CSI-Thai were successful, with satisfactory reliability and construct validity.Implications for rehabilitationCentral Sensitisation Inventory-Thai version (CSI-Thai) is successfully adapted and demonstrated satisfactory reliability and construct validity.The CSI-Thai can be applicable to assess central sensitisation-related signs and symptoms in Thai-speaking patients with chronic non-specific neck pain (CNSNP) both clinical and research purposes.The CSI-Thai correlated to pain, disability and quality of life among patients with CNSNP.

• Pre-morbid contexts may relate to the onset of central sensitisation in chronic low back pain. • Themes of developmental learning experiences and personal characteristics emerged. • Themes of physical and emotional sensitivities and traumas also emerged. • These four themes may be linked with autonomic stress responses and central sensitisation pain. Central sensitisation pain is a predominant mechanism in a proportion of individuals with non-specific chronic low back pain and is associated with poor outcomes. It is proposed that the pre-morbid experiences and contexts may be related to the development of central sensitisation. The objective of this study was to explore the pre-morbid experiences and personal characteristics of participants with central sensitisation pain from a non-specific chronic low back pain population. This was a qualitative, exploratory study, using a concurrent nested design within a mixed methods protocol. n = 9 participants were recruited purposively based on sensory profiles and trait anxiety-related personality types. Data were collected through semi structured interviews, managed using QSR NVivo 10 software and analysed using theoretical thematic analysis. Four themes emerged: developmental learning experiences, personal characteristics, sensitivity and trauma. Reported was lack of confidence, low esteem and a need to please others, physical hyper-sensitivities (smell, light, sound) and emotional sensitivity (anxiety) as well as physical hypo-sensitivity. Participants had also suffered emotional and/or physical trauma. Learning difficulties, sensory sensitivities and trauma are associated with autonomic stress responses, which in turn have been linked to physiological changes seen in central sensitisation pain. Central sensitisation pain developed in the context of sensory processing differences related to learning difficulties, sensitivities and trauma, and personal characteristics of low confidence and control, in a group of participants with non-specific chronic low back pain. The role of pre-existing sensory processing differences, as a component of altered central nervous system function, in relation to central sensitisation pain warrants further investigation. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Intravesically administered lidocaine is used in patients with bladder pain syndrome (BPS) to test the hypothesis that symptoms have a peripheral versus central mechanism. Methods: A cross-sectional study of 24 female patients with BPS was performed. The Central Sensitisation Inventory (CSI) and Kings Health Questionnaire (KHQ) were completed. Urodynamic assessment was undertaken. Women were asked to report their pain using a numeric rating scale at cystometric capacity and post void. Participants then received an intravesical instillation of either 20 ml of 2% alkalinised lidocaine (n = 16) or 20 ml of normal saline (n = 8). These solutions were allowed to remain in situ for 20 min and pain score repeated. Urodynamics was repeated. Results: There was a statistically significant volume increase following lidocaine treatment: maximal cystometric capacity (MCC) 192–261 ml post lidocaine (p = 0.005.) In contrast, there was no significant difference in the saline controls: MCC 190–183 ml (p = 0.879.) Individual analysis revealed five of 16 lidocaine participants did not respond to lidocaine. These five reported a significantly worse quality of life (QoL) than lidocaine responders and had a tendency towards central sensitivity syndromes. Conclusion: Lidocaine significantly improved MCC in 11/16 participants in this study. These patients appear to have peripherally mediated disease. However, the failure of response to treatment in five participants, as well as their tendency towards central sensitivity syndromes, implies that in this subgroup, a peripheral drive from the bladder is not critical to their pain, suggesting central nervous system (CNS) pathology. This simple and safe test could be used to stratify patients for research or therapeutic trials. [ABSTRACT FROM AUTHOR]

Background: Naloxone, an opioid receptor antagonist, is used as a pharmacological tool to detect tonic endogenous activation of opioid receptors in experimental pain models. We describe a pharmacokinetic model linking naloxone pharmacokinetics to its main metabolite after high-dose naloxone infusion.Methods: Eight healthy volunteers received a three-stage stepwise high-dose i.v. naloxone infusion (total dose 3.25 mg kg-1). Naloxone and naloxone-3-glucuronide (N3G) plasma concentrations were sampled from infusion onset to 334 min after infusion discontinuation. Pharmacokinetic analysis was performed using non-linear mixed effect models (NONMEM). The predictive performances of Dowling's and Yassen's models were evaluated, and target-controlled infusion simulations were performed.Results: Three- and two-compartment disposition models with linear elimination kinetics described the naloxone and N3G concentration time-courses, respectively. Two covariate models were developed: simple (weight proportional) and complex (with the shallow peripheral volume of distribution linearly increasing with body weight). The median prediction error (MDPE) and wobble for Dowling's model were -32.5% and 33.4%, respectively. For Yassen's model, the MDPE and wobble were 1.2% and 19.9%, respectively.Conclusions: A parent-metabolite pharmacokinetic model was developed for naloxone and N3G after high-dose naloxone infusion. No saturable pharmacokinetics were observed. Whereas Dowling's model was inaccurate and over-predicted naloxone concentrations, Yassen's model accurately predicted naloxone pharmacokinetics. The newly developed covariate models may be used for high-dose TCI-naloxone for experimental and clinical practice.Clinical Trials Registration: NCT01992146. [ABSTRACT FROM AUTHOR]

Neuropathic orofacial pain conditions represent a challenge to diagnose and treat. Natural substances are promising therapeutic options for the control of pain. This study aimed to examine whether (−)-α-bisabolol (BISA), a natural terpene, can attenuate nociceptive behaviour and central sensitisation in a rodent model of trigeminal neuropathic pain. Infraorbital nerve transection (IONX) or sham operation was performed in adult male rats. Head withdrawal thresholds as a measure of facial mechanical sensitivity were tested with von Frey monofilaments applied bilaterally to the facial vibrissal pad pre-operatively (baseline) and then post-operatively before and at 60, 120, 240 and 360 min after administration of vehicle control per oris (p.o.) or BISA (200 mg/kg p.o.) (n = 8/group). Effects of BISA or vehicle on the activity of nociceptive neurons recorded in the medullary dorsal horn (MDH) were tested on post - operative day 8–10. ANOVA followed by post-hoc Bonferroni tested for statistically significant differences (p < 0.05) across study groups and time points. IONX animals (but not sham or naïve animals) showed post-operative facial mechanical hypersensitivity that was unaffected by vehicle. However, administration of BISA at post-operative day 7 significantly reversed the mechanical hypersensitivity in IONX rats; this effect lasted for at least 6 h. BISA also attenuated IONX-induced central sensitisation of MDH nociceptive neurons, as reflected in reversal of their reduced activation thresholds, increased responses to graded mechanical stimuli and enhanced spontaneous activity. BISA may attenuate nociceptive behaviour and central sensitisation in a rat model of acute trigeminal neuropathic pain. [ABSTRACT FROM AUTHOR]

Introduction: Pain is considered to be one of a number of idiosyncratic, context-dependent 'protective actions' projected into the conscious domain by the central nervous system (CNS), as a result of a series of complex interactions in response to perceived threat. A model is described which proposes chronic pain and a variety of long-term, systemic functional neurological conditions to be a consequence of significant dysregulation of these protection systems. The Model: Previous research has demonstrated that a cognitive–behavioural model, first described in 1995 by Surawy et al., for chronic fatigue has been successful in predicting the transition from acute to chronic states in a number of conditions. This model includes predisposing, precipitating and perpetuating biopsychosocial factors. This article discusses the potential role of these factors in affecting descending inhibition in the CNS, significantly altering its ability to modulate the threat detection system. The development of 'central sensitisation' is considered in this context. Conclusion: This model proposes that chronic pain, chronic fatigue and other so-called functional neurological phenomena can, perhaps, be more helpfully seen as the actions of a dysregulated neurological protection system, rather than symptoms of an untreatable and deteriorating medical condition. Recommendations are made for the development of appropriate therapeutic interventions indicated by this model. [ABSTRACT FROM AUTHOR]

Review of a practical resource providing children with ongoing pain (and their parents) information of the neurobiology of pain. The book 'My Bodyguard Brain - How your brain uses pain to protect you' explains why we feel pain. The brain makes pain when it notices any sort of danger. Pain is associated with acute injury but it can also be evoked by social interaction and unpleasant emotion that children don't know how to deal with. The text and drawings explain in a child-friendly way how your 'Bodyguard' brain wants to look after you, and how it sometimes gets a bit 'too good' at that job. It is a book I would recommend for teachers and clinicians dealing with children experiencing chronic pain. Ongoing pain in children is a huge problem in society. Paediatric pain should matter to everyone. It affects approximately one quarter to one third of all children and adolescents. Children with chronic pain have often cut back all their normal activities like school, sports, social life and sleep. Almost 60% of these children become adults experiencing pain and 50% of the children with pain has a parent suffering from chronic pain. Understanding what you feel will turn the oversensitive alarm down and is the first step to improve the lives of children and adolescents with pain. [ABSTRACT FROM AUTHOR]

The purinergic P2Y12 receptor regulates microglial activation, resulting in persistence and aggravation of pain in neuropathic and nociceptive pain models. We conducted a retrospective chart review to explore the analgesic potency of the P2Y12 receptor-specific antagonist, clopidogrel, for clinical management of postoperative pain in patients who underwent abdominal surgery. Twenty-seven patients with cardiovascular comorbidities, who underwent laparoscopic abdominal surgery and had ceased aspirin (ASP, n = 17) or clopidogrel (CLP, n = 10) for 14 days pre-operatively, were enrolled retrospectively. In both groups, the number of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) consumed for managing postoperative pain was compared using the chi-square test and Mann–Whitney test. Our results showed that from postoperative day (POD) 0 to POD 3, the average numerical rating reflecting the postoperative pain was comparable between the two groups (CLP: 4.0 ± 1.4 vs. ASP: 3.7 ± 0.8, P-value = 0.56). However, at POD 7, opioid consumption in the CLP-treated group (fentanyl-equivalent dose: 0.49 ± 0.56 mg) was significantly lower than that in the ASP-treated group (1.48 ± 1.35 mg, P-value = 0.037). After reaching a stable state by repeated systemic administration, clopidogrel sustained the analgesic efficacy for a certain period. In conclusion, microglial P2Y12 receptors may mediate signal transduction of postoperative nociceptive pain and enhance clinical opioid analgesia.

Neurotrophins (NTs) belong to a family of trophic factors that regulate the survival, growth and programmed cell death of neurons. In mammals, there are four structurally and functionally related NT proteins, viz. nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 and neurotrophin 4. Most research on NTs to date has focussed on the effects of NGF and BDNF signalling via their respective cognate high affinity neurotrophic tyrosine kinase viz TrkA and TrkB receptors. Apart from the key physiologic roles of NGF and BDNF in peripheral and central nervous system function, NGF and BDNF signalling via TrkA and TrkB receptors respectively have been implicated in mechanisms underpinning neuropathic pain. Additionally, NGF and BDNF signalling via the low-affinity pan neurotrophin receptor at 75 kDa (p75NTR) may also contribute to the pathobiology of neuropathic pain. In this review, we critically assess the role of neurotrophins signalling via their cognate high affinity receptors as well as the low affinity p75NTR in the pathophysiology of peripheral neuropathic and central neuropathic pain. We also identify knowledge gaps to guide future research aimed at generating novel insight on how to optimally modulate NT signalling for discovery of novel therapeutics to improve neuropathic pain relief.

Introduction: The mechanism underlying endometriosis-related pain remains poorly understood. Previous studies have indicated that γ-aminobutyric acid (GABA) type A (GABA A ) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABA A receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABA A receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relation between GABA A receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABA A receptor, in the participating women., Material and Methods: 15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom-free, control women, aged 18-40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection., Results: Compared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABA A receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels., Conclusions: Women with painful endometriosis show altered GABA A receptor function, depicted as a muted response to an exogenous GABA A receptor agonist., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

In man, central sensitisation (CS) contributes to the pain of osteoarthritis (OA). Dogs with spontaneous OA may also exhibit CS. Electrophysiological reflex measurements are more objective than behavioural assessments and can be used to evaluate CS in preclinical and clinical studies. It was hypothesised that dogs suffering from OA would exhibit electrophysiological characteristics indicative of CS, associated with reduced diffuse noxious inhibitory controls (DNICs). One hundred and seventeen client-owned dogs were recruited to the study. Hind limb nociceptive withdrawal reflex thresholds, stimulus response, and temporal summation characteristics were recorded, during alfaxalone anaesthesia, from 46 OA dogs, 29 OA dogs receiving nonsteroidal anti-inflammatory drugs (OANSAIDs), and 27 breed- and weight-matched control dogs. Efficacy of DNIC was evaluated in 12 control and 11 of the OA dogs, by application of a mechanical conditioning stimulus to the contralateral forelimb. Nociceptive withdrawal reflex thresholds were higher in OA compared with control dogs (P = 0.02). Stimulus response characteristics demonstrated an augmented response in OANSAID dogs compared with OA (P < 0.001) and control (P < 0.001) dogs. Temporal summation demonstrated exaggerated C-fibre-mediated responses in both OA (P < 0.001) and OANSAID (P = 0.005) groups, compared with control animals. Conditioning stimulus application resulted in inhibition of test reflex responses in both OA and control animals (P < 0.001); control animals demonstrated greater inhibition compared with OA (P = 0.0499). These data provide evidence of neurophysiological changes consistent with CS in dogs with spontaneous OA and demonstrate that canine OA is associated with reduced DNIC. [ABSTRACT FROM AUTHOR]

Purpose of Review: Osteoarthritis (OA) is a major cause of pain and disability worldwide. There is, however, a relatively poor correlation between the severity of OA based on plain radiograph changes and symptoms. In this review, we consider the mechanisms of pain in OA.Recent Findings: It is now widely recognised that OA is a disease of the whole joint. Data from large observational studies which have used magnetic resonance imaging (MRI) suggest that pain in OA is associated with a number of structural factors including the presence of bone marrow lesions (BMLs) and also synovitis. There is evidence also of alterations in nerve processing and that both peripheral and central nerve sensitisation may contribute to pain in OA.Summary: Identification of the causes of pain in an individual patient may be of benefit in helping to better target with appropriate therapy to help reduce their symptoms and improve function. [ABSTRACT FROM AUTHOR]

Hereditary neuropathy with liability to pressure palsy (HNPP) has historically been considered a pain-free condition, though some people with HNPP also complain of pain. This study characterised persistent pain in people with HNPP. Participants provided cross-sectional demographic data, information on the presence of neurological and persistent pain symptoms, and the degree to which these interfered with daily life. The painDETECT and Central Sensitization Inventory questionnaires were used to indicate potential neuropathic, central sensitisation and musculoskeletal (nociceptive) pain mechanisms. Additionally, participants were asked if they thought that pain was related to/part of HNPP. 32/43 (74%) subjects with HNPP had persistent pain and experience this pain in the last week. Of those with pain, 24 (75%) were likely to have neuropathic pain and 27 (84%) were likely to have central sensitisation. All 32 participants felt that their pain could be related to/part of their HNPP. Significant negative impact of the pain was common. Pain characterisation identified neuropathic pain and/or central sensitisation as common, potential underlying processes. Pain may plausibly be directly related to the underlying pathophysiology of HNPP. Further consideration of including pain as a primary symptom of HNPP is warranted. [ABSTRACT FROM AUTHOR]

Background/objectives Chronic pancreatitis (CP) pain is challenging to treat. Treatment selection is hampered by there being no validated pain assessment tool that accounts for the complexity of CP pain and its underlying mechanisms. This study aims to develop a comprehensive pain assessment tool (COMPAT) specific for CP, evaluate its face validity with experts and patients and test it with a pilot cohort of patients. Methods COMPAT was developed from existing pain assessment tools and a literature review. Face validity was conducted by pancreatologists and CP patients using an item-content validity index for importance, relevance and clarity. Subsequent revisions were made to COMPAT. A pilot cohort of CP patients tested COMPAT. Results COMPAT was developed and covered all important aspects of CP pain. Experts and CP patients reported that 70% of questions were important and relevant to CP pain. Most experts were willing to use COMPAT in clinic, ward/hospital and research settings. The most common location of pain was the epigastrium and food was the most important trigger. Pain Pattern C (constant background pain with pain attacks), had significantly higher frequency of pain attacks, higher opioid use, and affective descriptors of pain than Pattern A (pain attacks with no background pain). Conclusions COMPAT has high face validity and met with high acceptance. CP patients successfully self-reported their pain with COMPAT. The results reveal many differences in the CP pain within the pilot cohort, which may reflect different mechanisms of pain. A larger prospective cohort study is planned to further validate COMPAT. [ABSTRACT FROM AUTHOR]

Upregulation of defensive reflexes such as the nociceptive flexion reflex (NFR) has been attributed to sensitisation of peripheral and spinal nociceptors and is often considered biomarkers of pain. Experimental modulation of defensive reflexes raises the possibility that they might be better conceptualised as markers of descending cognitive control. Despite strongly held views on both sides and several narrative reviews, there has been no attempt to evaluate the evidence in a systematic manner. We undertook a metaanalytical systematic review of the extant English-language literature from inception. Thirty-six studies satisfied our a priori criteria. Seventeen were included in the meta-analysis. Reflexive threshold was lower in people with clinical pain than it was in pain-free controls, but reflex size, latency, and duration were unaffected. The pattern of difference was not consistent with sensitisation of nociceptive neurones, as these changes were not isolated to the affected body part but was more consistent with top-down cognitive control reflective of heightened protection of body tissue. The pattern of modulation is dependent on potentially complex evaluative mechanisms. We offer recommendations for future investigations and suggest that defensive reflex threshold may reflect a biomarker of a broader psychological construct related to bodily protection, rather than sensitisation of primary nociceptors, spinal nociceptors, or pain. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FM) is the most commonly encountered chronic widespread pain (CWP) condition in rheumatology. In comparison to inflammatory arthritis (IA), it can seem ill defined with no clear understanding of the pathology and therefore no specific targeted treatment. This inevitably raises controversies and challenges. However, this is an outdated view perpetuated by poor teaching of pain at undergraduate and postgraduate levels, and the perennial problem of advances in relevant cross-speciality knowledge penetrating speciality silos. Research has provided a better understanding of the aetiopathology and FM is now regarded as a centralized pain state. Effective treatment is possible utilizing a multidisciplinary approach combining nonpharmacologic and pharmacologic treatments rooted in a biopsychosocial model. This article will provide a review of the mechanisms, diagnosis and treatment of FM, focus on some ongoing contentious issues and propose a change to the diagnostic terminology. [ABSTRACT FROM AUTHOR]

Chronic fatigue syndrome (CFS) is a debilitating disorder of unknown pathogenesis, characterised by fatigue, which is exacerbated after minimal exercise. We examined the effect of a single bout of aerobic exercise on leucocyte mRNA expression of genes putatively linked to exaggerated afferent signalling as an under-pinning of the fatigue state. A carefully-characterised sample of patients with CFS (N = 10) and healthy matched control participants (N = 12) were included. Participant ratings of fatigue and other symptoms, as well as blood samples, were obtained at baseline, and five other time-points up to 72 hours after 25 minutes of moderate-intensity cycling exercise. Leucocyte mRNA of 19 metabolite-sensing, adrenergic, immune and neurotransmission genes was examined using quantitative polymerase chain reaction. Patients with CFS reported substantial fatigue, functional impairment and poor sleep at baseline (all p < 0.02), and exercise immediately induced worsened patients’ fatigue (effect size, ES = 1.17). There were no significant changes in gene expression after exercise and patients did not differ from control participants at any time point. Higher levels of expression of ficolin (FCN1) and a purinergic receptor (P2RX4) in patients with CFS were found when all time points were combined. Patients with CFS did not show significant exercise-induced changes in leucocyte mRNA of 19 metabolite-sensing, adrenergic, immune and neurotransmission genes despite a prominent exacerbation of fatigue.

Background Patients with chronic pancreatitis (CP) frequently report chronic abdominal pain that adversely impacts their quality of life. Assessment of pain in CP is required for clinical management and clinical studies. International consensus guidelines recognized a lack of specific and validated pain assessment tools for CP. Therefore, the aim of this systematic review is to identify and compare all clinical studies that assessed pain in the context of a treatment for pain in CP. Methods A systematic literature search was performed in PubMed, Cochrane Library and Ovid MEDLINE. The search identified all intervention studies for pain in CP and the pain assessment tools used based on pre-defined inclusion and exclusion criteria. Results Of 341 articles identified, 137 studies were included. Pain assessment tools were both general and CP-specific. The latter were used in only 22 (16%) studies. Despite recommendations the aspects of pain assessed were limited and variable between tools. Validation of these tools in CP patients was limited to quality of life measures. None of the pain assessment tools evaluated duration of pain and postprandial pain. Conclusions There are no published pain assessment tools for CP that includes all relevant aspects of pain. There is the need to develop a comprehensive and validated pain assessment tool for patients with CP to standardised pain assessment, identify likely underlying pain mechanisms, help select appropriate treatments, report outcomes from interventions, improve clinical communication and aid the allocation of patients to clinical trials. [ABSTRACT FROM AUTHOR]

Chronic fatigue syndrome (CFS) is a debilitating disorder of unknown pathogenesis, characterized by fatigue, which is exacerbated after minimal exercise. We examined the effect of a single bout of aerobic exercise on leucocyte mRNA expression of genes putatively linked to exaggerated afferent signaling as an under-pinning of the fatigue state. A carefully-characterized sample of patients with CFS (N = 10) and healthy matched control participants (N = 12) were included. Participant ratings of fatigue and other symptoms, as well as blood samples, were obtained at baseline, and five other time-points up to 72 h after 25 min of moderate-intensity cycling exercise. Leucocyte mRNA of 19 metabolite-sensing, adrenergic, immune, and neurotransmission genes was examined using quantitative polymerase chain reaction. Patients with CFS reported substantial fatigue, functional impairment, and poor sleep at baseline (all p < 0.02), and exercise immediately induced worsened patients' fatigue (effect size, ES = 1.17). There were no significant changes in gene expression after exercise and patients did not differ from control participants at any time point. Higher levels of expression of ficolin (FCN1) and a purinergic receptor (P2RX4) in patients with CFS were found when all time points were combined. Patients with CFS did not show significant exercise-induced changes in leucocyte mRNA of 19 metabolite-sensing, adrenergic, immune and neurotransmission genes despite a prominent exacerbation of fatigue. [ABSTRACT FROM AUTHOR]

Introduction: Central sensitisation (CS) can't be demonstrated and thus only be assumed to be present in humans: Human Assumed Central Sensitization (HACS)1. The Central Sensitisation Inventory (CSI)2 is a screening instrument for HACS with a cut-off score of 40 (range 0-100) 3. This study aims to re-establish the optimal cut-off value for the CSI and to study associated factors. Methods: Via ROC-analyses we compared patients with chronic pain with healthy controls. Regression analysis was performed on factors (descriptives; pain-related characteristics) possibly associated with CSI-score. Results: Based on patients (n = 1730) and controls (n = 250), CSI cut-off values for the presence of HACS were established at =30 (women: = 33; men: = 25(table)). Regression analyses showed that the CSI-score was associated with all factors (adjusted R2 = 54-58%). A low association between the CSI-score and pain severity was shown in women and men separately. Discussion: In contrast with previous studies, a lower cut-off score is established for patients with chronic pain, being higher for women than for men. Process evaluation: The question rises whether CSI should be used with a dichotomous, categorical or continuous scale. More insight is needed in the presence of HACS and, the influence of sex, other characteristics and specific sub-populations of patients. [ABSTRACT FROM AUTHOR]

Long-term potentiation in the spinal dorsal horn requires peptidergic C-fibre activation in animals. Perceptual correlates of long-term potentiation following high-frequency electrical stimulation in humans include increased sensitivity to electrical stimuli at the high frequency stimulation site (homotopic pain-long-term potentiation) and increased sensitivity to pinprick surrounding the high frequency stimulation site (heterotopic pain-long-term potentiation, equivalent to secondary hyperalgaesia). To characterize the peripheral fibre populations involved in induction of pain-long-term potentiation, we performed two selective nerve block experiments in 30 healthy male volunteers. Functional blockade of TRPV1-positive nociceptors by high-concentration capsaicin (verified by loss of heat pain) significantly reduced pain ratings to high frequency stimulation by 47% (P < 0.001), homotopic pain-long-term potentiation by 71% (P < 0.01), heterotopic pain-long-term potentiation by 92% (P < 0.001) and the area of secondary hyperalgesia by 76% (P < 0.001). The selective blockade of A-fibre conduction by nerve compression (verified by loss of first pain to pinprick) significantly reduced pain ratings to high frequency stimulation by 37% (P < 0.01), but not homotopic pain-long-term potentiation (-5%). It had a marginal effect on heterotopic pain-long-term potentiation (-35%, P = 0.059), while the area of secondary hyperalgesia remained unchanged (-2%, P = 0.88). In conclusion, all nociceptor subclasses contribute to high frequency stimulation-induced pain (with a relative contribution of C > A? fibres, and an equal contribution of TRPV1-positive and TRPV1-negative fibres). TRPV1-positive C-fibres are the main inducers of both homotopic and heterotopic pain-long-term potentiation. TRPV1-positive A-fibres contribute substantially to the induction of heterotopic pain-long-term potentiation. TRPV1-negative C-fibres induce a component of homotopic self-facilitation but not heterotopic pain-long-term potentiation. TRPV1-negative A-fibres are the main afferents mediating pinprick pain and hyperalgesia, however, they do not appear to contribute to the induction of pain-long-term potentiation. These findings show that distinct peripheral fibre classes mediate induction of long-term potentiation-like pain amplification, its spatial spread to adjacent skin (i.e. secondary hyperalgesia), and the resulting enhanced sensitivity to pinprick in humans. Nociceptive afferents that induce pain amplification can be readily dissociated from those mediating pain. These findings add substantially to our understanding of the mechanisms of pain amplification, that form the basis for understanding the mechanisms of hyperalgesia encountered in patients.See Sandkühler (doi:10.1093/brain/awv193) for a scientific commentary on this article. [ABSTRACT FROM AUTHOR]

Neurotrophins (NTs) belong to a family of trophic factors that regulate the survival, growth and programmed cell death of neurons. In mammals, there are four structurally and functionally related NT proteins, viz. nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 and neurotrophin 4. Most research on NTs to date has focussed on the effects of NGF and BDNF signalling via their respective cognate high affinity neurotrophic tyrosine kinase viz TrkA and TrkB receptors. Apart from the key physiologic roles of NGF and BDNF in peripheral and central nervous system function, NGF and BDNF signalling via TrkA and TrkB receptors respectively have been implicated in mechanisms underpinning neuropathic pain. Additionally, NGF and BDNF signalling via the low-affinity pan neurotrophin receptor at 75 kDa (p75NTR) may also contribute to the pathobiology of neuropathic pain. In this review, we critically assess the role of neurotrophins signalling via their cognate high affinity receptors as well as the low affinity p75NTR in the pathophysiology of peripheral neuropathic and central neuropathic pain. We also identify knowledge gaps to guide future research aimed at generating novel insight on how to optimally modulate NT signalling for discovery of novel therapeutics to improve neuropathic pain relief. [ABSTRACT FROM AUTHOR]

Objectives Functional somatic syndromes are common and disabling conditions that all include chronic pain, and which may be related to central nervous system sensitisation. Here, we address the concept of central sensitisation as a physiological basis for the functional somatic syndromes. Methods A narrative review of the current literature on central sensitisation and physiological studies in the functional somatic syndromes. Results Central sensitisation may be a common neurophysiological process that is able to explain non-painful as well as painful symptoms in these disorders. Furthermore, central sensitisation may represent an endophenotypic vulnerability to the development of these syndromes that potentially explains why they cluster together. Conclusions Further research is needed to verify these findings, including prospective studies and the standardisation of combined methods of investigation in the study of central sensitisation in functional somatic syndromes. In turn, this may lead to new explanatory mechanisms and treatments being evaluated. Our conclusions add to the debate over the nomenclature of these syndromes but importantly also provide an explanation for our patients. [ABSTRACT FROM AUTHOR]

In healthy participants, high-frequency electrical stimulation of the forearm not only evokes local hyperalgesia but also inhibits sensitivity to pressure-pain in the ipsilateral forehead, possibly due to activation of ipsilateral inhibitory pain modulation processes. The aim of this study was to compare the effects of high- and low-frequency electrical stimulation of the forearm on sensitivity to pressure-pain in the ipsilateral forehead, as inhibitory pain modulation may be stronger after low- than high-frequency electrical stimulation. Before and after high- and low-frequency electrical stimulation, sensitivity to heat and to blunt and sharp stimuli was assessed at and adjacent to the electrically conditioned site in the forearm. In addition, sensitivity to blunt pressure was measured bilaterally in the forehead. Pain was more intense after high- than low-frequency electrical stimulation and was followed by primary and secondary hyperalgesia to mechanical stimulation after high- but not low-frequency electrical stimulation. Nevertheless, sensitivity to pressure-pain decreased to the same extent in the ipsilateral forehead after both forms of electrical stimulation. This decrease was associated with heightened sensitivity to pressure-pain at the electrically conditioned forearm site and with diminished sensitivity to heat around this site. These findings suggest that sensitisation of pressure-sensitive nociceptive afferents at the site of electrical stimulation is associated with generation of an ipsilateral pain-inhibitory process. This ipsilateral pain-inhibitory process may decrease sensitivity to pressure-pain in the ipsilateral forehead and suppress secondary hyperalgesia to heat. [ABSTRACT FROM AUTHOR]

Highlights: [•] A model that can predict pain intensity in knee osteoarthritis (KOA) is proposed. [•] 55% of the variability in pain can be explained by two pain measures in KOA. [•] The pain measures reflect spreading sensitisation and temporal summation. [•] This underlines the importance of central pain mechanisms in KOA pain management. [Copyright &y& Elsevier]

Objective: The aim of the present study is to evaluate the presence and frequency of central sensitisation (CS) in primary Sjögren Syndrome (pSS) and to determine the effect of CS on sleep quality., Materials and Methods: In this cross-sectional study, 50 patients diagnosed with pSS between the ages of 18 and 75 were included. The healthy control group was composed of 43 healthcare workers. Each participant underwent a physical examination, and demographic data and the medications they used were recorded. Central sensitisation inventory and Pittsburgh Sleep Quality Index questionnaires were filled in to garner data on CS and sleep quality, respectively, from all participants., Results: While central sensitisation inventory  >40 was detected in 74% of pSS patients, it was 25.6% in healthy controls, and there is a statistically significant difference between the groups (p < .05). A correlation analysis of the central sensitisation inventory and Pittsburgh Sleep Quality Index values of all participants revealed a statistically significant correlation between all parameters other than the duration of sleep (p < .05)., Conclusions: CS was found to have a negative effect on sleep quality in patients with pSS. We suggest that the cause of widespread pain seen in patients with pSS as the possible development of CS should be considered., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a debilitating condition characterised by bladder/pelvic pain and pressure as well as persistent or recurrent urinary symptoms in the absence of an identifiable cause. It is hypothesised that in addition to organ specific visceral hypersensitivity, contributions of the hypertonic pelvic floor, peripheral sensitisation, and central sensitisation exacerbate this condition. The aim of this paper is to investigate outcomes of treating underlying neuromuscular dysfunction and neuro-plastic mechanisms in BPS/IC patients., Methods: A retrospective chart review of 84 patients referred to an outpatient pelvic rehabilitation centre with a diagnosis of BPS/IC given to them by a urologist. All 84 patients failed to progress after completing 6 weeks of pelvic floor physical therapy and underwent an institutional review board approved protocol (IRB# 17-0761) consisting of external ultrasound-guided trigger point injections to the pelvic floor musculature, peripheral nerve blocks of the pudendal and posterior femoral cutaneous nerves and continued pelvic floor physical therapy once weekly for 6 weeks. Pelvic pain intensity and functionality were measured pretreatment and 3 months posttreatment using Visual Analogue Scale (VAS) and Functional Pelvic Pain Scale (FPPS)., Results: Pretreatment, mean VAS was 6.23 ± 2.68 (95% CI 5.65 to 6.80). Posttreatment mean VAS was 3.90 ± 2.63 (95% CI 3.07-4.74). Mean FPPS before treatment was 11.98 ± 6.28 (95% CI 10.63 to 13.32). Posttreatment mean FPPS was 7.68 ± 5.73 (95% CI 6.45-8.90). Analysis of subcategories within FPPS indicated highest statistically significant improvement in the categories of bladder, intercourse and working., Conclusions: Analysis suggests the treatment was effective at ameliorating bladder pain and function including urinary urgency, frequency, and burning in BPS/IC patients., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Rheumatic pain and, in particular, rheumatoid arthritis, osteoarthritis and fibromyalgia, are common and debilitating chronic pain syndromes. Recently, human functional neuroimaging, for example EEG, fMRI, and PET has begun to reveal some of the crucial central nervous system mechanisms underlying these diseases. The purpose of this review is to summarise current knowledge on the brain mechanisms of rheumatic pain revealed by functional neuroimaging techniques. The evidence suggests that two mechanisms may be largely responsible for the clinical pain associated with these rheumatic diseases: abnormalities in the medial pain system and/or central nervous system sensitisation and inhibition. If we can understand how functioning of the central nociceptive system becomes altered, even in the absence of peripheral nociceptive input, by using functional neuroimaging techniques, in the future we may be able to develop improved, more effective treatments for patients with chronic rheumatic pain. [ABSTRACT FROM AUTHOR]

Abstract: As a mechanisms-based classification of pain ‘central sensitisation pain’ (CSP) refers to pain arising from a dominance of neurophysiological dysfunction within the central nervous system. Symptoms and signs associated with an assumed dominance of CSP in patients attending for physiotherapy have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of CSP in patients with low back (±leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (±leg) pain were assessed using a standardised assessment protocol. Patients’ pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist specifying the presence or absence of various clinical criteria. A binary logistic regression analysis with Bayesian model averaging identified a cluster of three symptoms and one sign predictive of CSP, including: ‘Disproportionate, non-mechanical, unpredictable pattern of pain provocation in response to multiple/non-specific aggravating/easing factors’, ‘Pain disproportionate to the nature and extent of injury or pathology’, ‘Strong association with maladaptive psychosocial factors (e.g. negative emotions, poor self-efficacy, maladaptive beliefs and pain behaviours)’ and ‘Diffuse/non-anatomic areas of pain/tenderness on palpation’. This cluster was found to have high levels of classification accuracy (sensitivity 91.8%, 95% confidence interval (CI): 84.5–96.4; specificity 97.7%, 95% CI: 95.6–99.0). Pattern recognition of this empirically-derived cluster of symptoms and signs may help clinicians identify an assumed dominance of CSP in patients with low back pain disorders in a way that might usefully inform their management. [Copyright &y& Elsevier]