Individuals With Prior Chronic Pain and Long-Term Opioid Treatment May Experience Persistence of That Pain Even After Subsequent Complete Cervical Spinal Cord Injury: Suggestions From a Prospective Case-Controlled Study.

Objective: To determine whether chronic pain persists after complete spinal cord injury (SCI). Design: Prospective observational study regarding the outcome of pre-existent chronic pain of inpatients admitted with new clinically diagnosed complete cervical SCI. For patients who acknowledged chronic pain of ≥3 years duration before the SCI, further questions explored whether they still experienced that pain, whether they were experiencing current posttraumatic pain, and whether they had any past exposure to opioids. The included patients were identified during the initial consultation in the trauma center for treatment of the SCI. Setting: Level I trauma center. Participants: From a total of 49 participants with acute cervical SCI with clinically diagnosed complete motor and sensory tetraplegia admitted between 2018 and 2020, 7 were selected on the basis of a history of chronic pain. Intervention: Collected complete history and performed physical examination with serial follow-ups during the acute hospital stay until death or discharge. Main Outcome Measures: The primary outcome was a finding of chronic pain experienced before new clinical diagnosis of complete SCI, compared with whether or not that pain continued after the SCI injury. The secondary outcome was the relation of persistent pain with opioid use; it was formulated after data collection. Results: Among 49 patients with clinically diagnosed complete cervical SCIs, 7 had experienced prior chronic pain. Four participants experienced a continuation of the prior pain after their complete tetraplegia (4/7), whereas 3 participants did not (3/7). All the participants with continued pain had been previously treated with opioids, whereas those whose pain ceased had not received chronic opioid therapy. Conclusions: There may be a unique form of chronic pain that is based in the brain, irrespective of peripheral pain or spinal mechanisms. Otherwise healthy people with longstanding antecedent chronic pain whose pain persists after acute clinically complete SCI with tetraplegia may provide a new model for evaluation of brain-based pain. Opioids may be requisite for this type of pain.

Oxycodone or Higher Dose of Levodopa for the Treatment of Parkinsonian Central Pain: OXYDOPA Trial.

BACKGROUND: Among the different types of pain related to Parkinson's disease (PD), parkinsonian central pain (PCP) is the most disabling. OBJECTIVES: We investigated the analgesic efficacy of two therapeutic strategies (opioid with oxycodone- prolonged-release (PR) and higher dose of levodopa/benserazide) compared with placebo in patients with PCP. METHODS: OXYDOPA was a randomized, double-blind, double-dummy, placebo-controlled, multicenter parallel-group trial run at 15 centers within the French NS-Park network. PD patients with PCP (≥30 on the Visual Analogue Scale [VAS]) were randomly assigned to receive oxycodone-PR (up to 40 mg/day), levodopa/benserazide (up to 200 mg/day) or matching placebo three times a day (tid) for 8 weeks at a stable dose, in add-on to their current dopaminergic therapy. The primary endpoint was the change in average pain intensity over the previous week rated on VAS from baseline to week-10 based on modified intention-to-treat analyses. RESULTS: Between May 2016 and August 2020, 66 patients were randomized to oxycodone-PR (n = 23), levodopa/benserazide (n = 20) or placebo (n = 23). The mean change in pain intensity was -17 ± 18.5 on oxycodone-PR, -8.3 ± 11.1 on levodopa/benserazide, and -14.3 ± 18.9 in the placebo groups. The absolute difference versus placebo was -1.54 (97.5% confidence interval [CI], -17.0 to 13.90; P = 0.8) on oxycodone-PR and +7.79 (97.5% CI, -4.99 to 20.58; P = 0.2) on levodopa/benserazide. Similar proportions of patients in each group experienced all-cause adverse events. Those leading to study discontinuation were most frequently observed with oxycodone-PR (39%) than levodopa/benserazide (5%) or placebo (15%). CONCLUSIONS: The present trial failed to demonstrate the superiority of oxycodone-PR or a higher dose of levodopa in patients with PCP, while oxycodone-PR was poorly tolerated. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Repetitive transcranial magnetic stimulation in central post-stroke pain: a meta-analysis and systematic review of randomized controlled trials.

Background: The rehabilitation of central post-stroke pain (CPSP) is a complex clinical challenge, and repetitive transcranial magnetic stimulation (rTMS) has been widely applied in the research of neurofunctional recovery following stroke. However, there is currently no reliable evidence-based medicine supporting the efficacy of rTMS in central post-stroke pain. This review aims to evaluate the effects of rTMS on central post-stroke pain. Methods: Following the PRISMA guidelines, we conducted searches on PubMed, Cochrane Library, Embase, Web of Science, CNKI, and Wan Fang Data Knowledge Service Platform. We searched for randomized controlled trials (RCTs) investigating the use of rTMS in treating central post-stroke pain, and conducted screening based on inclusion and exclusion criteria. Characteristics of the included RCTs were extracted. The heterogeneity of the trials was assessed using the I2 statistic. Meta-analysis was performed using Stata 17 software. Bias risk and methodological quality were evaluated using the Cochrane RoB 2 tool and the Pedro scale. Results: A total of six randomized controlled trials involving 288 patients met our inclusion criteria. In our analysis, rTMS was more effective in treating patients with CPSP compared to the placebo group (SMD=-1.15, 95% CI: -1.69, -0.61, P < 0.001). Furthermore, results from subgroup analysis indicated no statistically significant difference in the improvement of pain for durations exceeding 6 months when comparing rTMS to conventional treatment (SMD=-0.80, 95% CI: -1.63, 0.03, P = 0.059). Conclusion: TMS can alleviate pain in CPSP patients and improve their motor function, but its effects on depression, anxiety, and MEP-latency are not significant. Systematic review registration: https://www.crd.york.ac.uk/prospero/, CRD42024497530.

Neuropathic and Nociplastic Pain Profiles are Common in Adult Chronic Nonbacterial Osteitis (CNO).

Chronic nonbacterial osteitis (CNO) is a rare musculoskeletal disease causing chronic bone pain. It is known that chronic musculoskeletal pain may involve other mechanisms than nociceptive pain only. We investigate the prevalence of neuropathic and nociplastic pain in adult CNO and their association with clinical characteristics and treatment outcomes. Survey study among the Dutch adult CNO cohort (n = 84/195 participated), including PAIN-detect for neuropathic pain, and the Central Sensitization Inventory (CSI), Fibromyalgia Rapid Screening Tool (FiRST), and ACTTION-APS Pain Taxonomy (AAPT) for nociplastic pain. Clinical characteristics and CNO-related bone pain scores were compared between patients with exclusive nociceptive pain and those with nociceptive pain plus neuropathic and/or nociplastic pain (mixed pain). 31% (95% CI 21-41) of patients classified as likely having neuropathic pain according to PAIN-detect. 53% (41-64) of patients displayed central sensitization on CSI, 61% (50-72) screened positive for fibromyalgia on FiRST and 14% (7-23) of patients fulfilled the AAPT criteria, all indicative of nociplastic pain. Mixed pain was associated with longer diagnostic delay (mean difference 2.8 years, 95% CI 0.4-5.2, p = 0.023), lower educational level (72% versus 20%, p < 0.001), and opioid use (37% versus 13%, p = 0.036). Despite comparable disease severity and extent, patients with mixed pain reported significantly higher CNO-related bone pain scores. This study demonstrates the high prevalence of mixed pain in adult CNO, in which neuropathic and nociplastic pain exist alongside nociceptive inflammatory bone pain. Disease burden in CNO may extend beyond inflammatory activity, highlighting the need for a multifaceted management approach.

Cingulotomy: the last man standing in the battle against medically refractory poststroke pain.

Introduction: Central poststroke pain (CPSP) places a huge burden on patient lives because patients are often refractory to conventional strategies and have little chance for spontaneous recovery. A subset of patients is even given approval for euthanasia and is without any perspective. Because the anterior cingulate cortex historically seems to be a promising target for patients with both mental and chronic pain disorders, lesioning of this central "hub" with cingulotomy may be a useful strategy for medically refractory CPSP. However, limited research is available on cingulotomy for central pain. Hence, we represent a rare case in which cingulotomy is performed on a patient with CPSP. Objectives: To describe the potential of cingulotomy in a case with CPSP. Methods: The case presented in this study concerns a 60-year-old woman who experienced CPSP, caused by a hemorrhagic stroke in the basal ganglia and thalamus. The patient visited several centers and tried multiple off-label treatments; however, she was told nothing else could be done and was even given approval for euthanasia. Hence, anterior cingulotomy was performed. Results: After surgery, no transient adverse events occurred, except for vocabulary disturbances post stroke, which disappeared after several weeks. After 14 weeks, changes in pain behavior were observed, followed by a decreased pain intensity. At a later follow-up, the pain had completely disappeared. Conclusion: Anterior cingulotomy seems to be a suitable "last-resort" option for patients with CPSP. Future research, including homogenous groups, to define the best location for lesioning is required to allow the revival of this "old" technique in the current era.

Relationship of migraine and other forms of chronic pain.

The disability of migraine, a highly prevalent condition, is worsened by a second comorbid chronic pain condition. There is evidence of a relationship between migraine and several visceral pain conditions including irritable bowel syndrome, endometriosis, and dysmenorrhoea, as well as nonvisceral conditions including temporomandibular dysfunction, fibromyalgia, and lower back pain. While the mechanisms linking these conditions are inadequately surmised, a two-way relationship between migraine and these comorbidities likely exists. The progression and chronification of migraine is associated with peripheral and central sensitization, which may predispose to other conditions. Conversely, aspects of the mechanism of each comorbid condition may promote further migraine attacks. This chapter introduces each comorbidity, briefly summarizes the existing evidence, and discusses implications for treatment.

Conditioned pain modulation and psychological factors in young adults with recurrent or chronic neck pain.

BACKGROUND: Controversy exists with the presence of alterations in descending pain inhibition mechanisms in patients with non-specific neck pain (NSNP). The aim of the present study was to evaluate the status of conditioned pain modulation CPM, remote pressure pain thresholds (PPT), and psychological factors in a specific subgroup of patients with NSNP such as young adult students. In addition, possible associations between CPM, psychological factors, and pain characteristics were analyzed. METHODS: Thirty students with recurrent or chronic NSNP and 30 pain-free students were included in this cross-sectional study. The following measures were assessed: CPM, remote PPT, psychological factors (depression, anxiety, pain catastrophizing, and kinesiophobia), pain characteristics (duration, intensity, severity of chronic pain, interference with daily life), and central sensitization inventory (CSI). RESULTS: No significant differences were found in the efficacy of CPM between students with chronic or recurrent NSNP and pain-free students (ß coefficient = -0.67; 95% CI = -1.54, 0.20). However, students with pain showed a significantly higher remote PPT (mean difference = -1.94; 95% CI = -2.71, -1.18). and a greater presence of anxious (mean difference = 6; 95% CI = 2, 9) and depressive symptoms (mean difference = 8.57; 95% CI = 3.97, 13.16). In addition, significant moderate or strong correlations were found between CPM and pain intensity (partial r = 0.41), pain catastrophizing and mean pain intensity (r = 0.37), grade (r = 0.50), and interference of pain (r = 0.57), kinesiophobia and disability (r = 0.38), and depression and CSI (r = 0.39). CONCLUSIONS: Young adult students with chronic or recurrent NSNP present remote hyperalgesia and symptoms of depression and anxiety but not dysfunctional CPM.

Exploration of the clinical course and longitudinal correlations in frozen shoulder: The role of autonomic function, central pain processing, and psychological variables. A longitudinal multicenter prospective observational study.

BACKGROUND: Altered central pain processing (CPP) and dysautonomia might play a role in the clinical course of frozen shoulder and psychological factors, like pain catastrophizing and hypervigilance, might influence clinical variables in frozen shoulder. OBJECTIVES: To explore the clinical course of frozen shoulder regarding CPP, dysautonomia, pain catastrophizing, and hypervigilance and to explore whether longitudinal correlations between these outcomes and pain intensity were present. DESIGN: prospective longitudinal observational study. METHOD: Participants with frozen shoulder were recruited at hospitals and general practitioner practices and followed for 9 months. They completed six questionnaires (about demographics, shoulder pain and disability, pain intensity, pain catastrophizing, pain hypervigilance, and autonomic symptoms) and underwent tactile sensitivity (allodynia), pressure pain thresholds (hyperalgesia), temporal summation, and conditioned pain modulation during four timeframes (3-month intervals). RESULTS: Initially, 149 participants with frozen shoulder were recruited and 88 completed all the measurements. An improvement from baseline to at least one follow-up measurement was found for shoulder pain and disability, pain intensity, pain catastrophizing, hypervigilance, and dysautonomia. A fair longitudinal correlation was found between pain intensity and catastrophizing and hypervigilance (r = 0.301-0.397). Poor longitudinal correlations were found between pain intensity and allodynia and hyperalgesia (r = -0.180-0.193), between pain catastrophizing and dysautonomia (r = 0.209) and between hypervigilance and hyperalgesia (r = -0.159). CONCLUSION: Patients with frozen shoulder showed an early improvement that flattened with time in several pain and psychological variables over the course of 9 months. However, autonomic symptoms rather showed a late improvement over 9 months.

Manual Therapy Effects on Nonspecific Neck Pain Are Not Mediated by Mechanisms Related to Conditioned Pain Modulation: A Randomized Clinical Trial.

BACKGROUND: Manual therapy (MT) is a treatment recommended by clinical practice guidelines in the management of patients with neck pain. However, the mechanisms through which MT works remain unknown. The aim of the present study is to investigate if MT is mediated by mechanisms related to conditioned pain modulation (CPM), comparing the effects of painful with a pain-free MT treatment. METHODS: A two-arm, parallel, randomized controlled clinical trial with concealed allocation and blinding of the outcome assessor was conducted in university students with chronic or recurrent nonspecific neck pain (NSNP). Participants received either a painful or pain-free MT session. Psychophysical variables including pressure pain thresholds, CPM, temporal summation of pain and cold pain intensity were assessed before and immediately after treatment. In addition, changes in neck pain intensity over the following 7 days and self-perceived improvement immediately and 7 days after treatment were assessed. RESULTS: No significant differences were found between groups in any of the psychophysical variables or in patients' self-perceived improvement. Only a significantly greater decrease in neck pain intensity immediately after treatment was found in the pain-free MT group compared to the painful MT group. CONCLUSION: The results suggest that the immediate and short-term effects of MT on NSNP are not mediated by CPM-related mechanisms.

Alterations of pain pathways by experimental sleep disturbances in humans: central pain-inhibitory, cyclooxygenase, and endocannabinoid pathways.

STUDY OBJECTIVES: There is strong evidence that sleep disturbances are an independent risk factor for the development of chronic pain conditions. The mechanisms underlying this association, however, are still not well understood. We examined the effect of experimental sleep disturbances (ESDs) on three pathways involved in pain initiation/resolution: (1) the central pain-inhibitory pathway, (2) the cyclooxygenase (COX) pathway, and (3) the endocannabinoid (eCB) pathway. METHODS: Twenty-four healthy participants (50% females) underwent two 19-day long in-laboratory protocols in randomized order: (1) an ESD protocol consisting of repeated nights of short and disrupted sleep with intermittent recovery sleep; and (2) a sleep control protocol consisting of nights with an 8-hour sleep opportunity. Pain inhibition (conditioned pain modulation, habituation to repeated pain), COX-2 expression at monocyte level (lipopolysaccharide [LPS]-stimulated and spontaneous), and eCBs (arachidonoylethanolamine, 2-arachidonoylglycerol, docosahexaenoylethanolamide [DHEA], eicosapentaenoylethanolamide, docosatetraenoylethanolamide) were measured every other day throughout the protocol. RESULTS: The central pain-inhibitory pathway was compromised by sleep disturbances in females, but not in males (p < 0.05 condition × sex effect). The COX-2 pathway (LPS-stimulated) was activated by sleep disturbances (p < 0.05 condition effect), and this effect was exclusively driven by males (p < 0.05 condition × sex effect). With respect to the eCB pathway, DHEA was higher (p < 0.05 condition effect) in the sleep disturbance compared to the control condition, without sex-differential effects on any eCBs. CONCLUSIONS: These findings suggest that central pain-inhibitory and COX mechanisms through which sleep disturbances may contribute to chronic pain risk are sex specific, implicating the need for sex-differential therapeutic targets to effectively reduce chronic pain associated with sleep disturbances in both sexes. CLINICAL TRIALS REGISTRATION: NCT02484742: Pain Sensitization and Habituation in a Model of Experimentally-induced Insomnia Symptoms. https://clinicaltrials.gov/ct2/show/NCT02484742.

IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice.

Chronic stress causes several pain conditions including fibromyalgia. Its pathophysiological mechanisms are unknown, and the therapy is unresolved. Since the involvement of interleukin-1 (IL-1) has been described in stress and inflammatory pain but no data are available regarding stress-induced pain, we studied its role in a chronic restraint stress (CRS) mouse model. Female and male C57Bl/6J wild-type (WT) and IL-1αß-deficient (knock-out: IL-1 KO) mice were exposed to 6 h of immobilization/day for 4 weeks. Mechanonociception, cold tolerance, behavioral alterations, relative thymus/adrenal gland weights, microglia ionized calcium-binding adaptor molecule 1 (IBA1) and astrocyte glial fibrillary acidic protein (GFAP) integrated density, number and morphological transformation in pain-related brain regions were determined. CRS induced 15-20% mechanical hyperalgesia after 2 weeks in WT mice in both sexes, which was significantly reduced in female but not in male IL-1 KOs. Increased IBA1+ integrated density in the central nucleus of amygdala, primary somatosensory cortex hind limb representation part, hippocampus cornu ammonis area 3 (CA3) and periaqueductal gray matter (PAG) was present, accompanied by a cell number increase in IBA1+ microglia in stressed female WTs but not in IL-1 KOs. CRS induced morphological changes of GFAP+ astrocytes in WT but not in KO mice. Stress evoked cold hypersensitivity in the stressed animals. Anxiety and depression-like behaviors, thymus and adrenal gland weight changes were detectable in all groups after 2 but not 4 weeks of CRS due to adaptation. Thus, IL-1 mediates chronic stress-induced hyperalgesia in female mice, without other major behavioral alterations, suggesting the analgesic potentials of IL-1 in blocking drugs in stress-related pain syndromes.

Corticomotor excitability is altered in central neuropathic pain compared with non-neuropathic pain or pain-free patients.

OBJECTIVES: Central neuropathic pain (CNP) is associated with altered corticomotor excitability (CE), which can potentially provide insights into its mechanisms. The objective of this study is to describe the CE changes that are specifically related to CNP. METHODS: We evaluated CNP associated with brain injury after stroke or spinal cord injury (SCI) due to neuromyelitis optica through a battery of CE measurements and comprehensive pain, neurological, functional, and quality of life assessments. CNP was compared to two groups of patients with the same disease: i. with non-neuropathic pain and ii. without chronic pain, matched by sex and lesion location. RESULTS: We included 163 patients (stroke=93; SCI=70: 74 had CNP, 43 had non-neuropathic pain, and 46 were pain-free). Stroke patients with CNP had lower motor evoked potential (MEP) in both affected and unaffected hemispheres compared to non- neuropathic pain and no-pain patients. Patients with CNP had lower amplitudes of MEPs (366 µV ±464 µV) than non-neuropathic (478 ±489) and no-pain (765 µV ± 880 µV) patients, p < 0.001. Short-interval intracortical inhibition (SICI) was defective (less inhibited) in patients with CNP (2.6±11.6) compared to no-pain (0.8±0.7), p = 0.021. MEPs negatively correlated with mechanical and cold-induced allodynia. Furthermore, classifying patients' results according to normative data revealed that at least 75% of patients had abnormalities in some CE parameters and confirmed MEP findings based on group analyses. DISCUSSION: CNP is associated with decreased MEPs and SICI compared to non-neuropathic pain and no-pain patients. Corticomotor excitability changes may be helpful as neurophysiological markers of the development and persistence of pain after CNS injury, as they are likely to provide insights into global CE plasticity changes occurring after CNS lesions associated with CNP.

Neuropathic Pain in Parkinson's Disease.

Pain is a well-recognized and important non-motor manifestation in Parkinson disease (PD). Painful or unpleasant sensations in PD can be classified as musculoskeletal, dystonia, akathisia, radicular, and central or primary pain; the last two are associated with neuropathic pain. Particularly, neuropathic pain in PD has not been fully clarified; therefore, it goes somewhat unnoticed, and the affected patients do not receive adequate pain treatment. The main purpose of this literature review was to identify the incidence of neuropathic pain in PD and the involvement of dopamine of this type of pain by the integration of different lines of investigation. In this review, a search was conducted using PubMed, ProQuest, EBSCO, Medline, EMBASE, and the Science Citation index for studies evaluating pain in patients with PD. The inclusion criteria were as follows: original articles that evaluated incidence and possible mechanism of neuropathic, central, and radicular pain in PD. Nine studies related to the incidence of neuropathic pain in PD suggest the activation of cerebral areas, such as the cortex, striatum, amygdala, thalamus, raphe nuclei, and locus coeruleus. Neuropathic pain is related to altered levels of dopamine, serotonin, and norepinephrine; these neurotransmitters are related to the sensitive and emotional dimensions of pain. Dopamine could cause hypersensitivity to pain, either indirectly through modulatory effects on affective pain processing and/or directly by affecting the neural activity in key areas of the brain that modulate pain. A considerable proportion of patients with PD suffer neuropathic pain; however, it has been disregarded, this has led to an inability to achieve an adequate treatment and a decrease in pain to improve the quality of life of these patients. We consider that neuropathic pain in PD is possibly induced by neurophysiological changes due to the degradation of dopaminergic neurons.

The Management of Poststroke Thalamic Pain: Update in Clinical Practice.

Poststroke thalamic pain (PS-TP), a type of central poststroke pain, has been challenged to improve the rehabilitation outcomes and quality of life after a stroke. It has been shown in 2.7-25% of stroke survivors; however, the treatment of PS-TP remains difficult, and in majority of them it often failed to manage the pain and hypersensitivity effectively, despite the different pharmacotherapies as well as invasive interventions. Central imbalance, central disinhibition, central sensitization, other thalamic adaptative changes, and local inflammatory responses have been considered as its possible pathogenesis. Allodynia and hyperalgesia, as well as the chronic sensitization of pain, are mainly targeted in the management of PS-TP. Commonly recommended first- and second-lines of pharmacological therapies, including traditional medications, e.g., antidepressants, anticonvulsants, opioid analgesics, and lamotrigine, were more effective than others. Nonpharmacological interventions, such as transcranial magnetic or direct current brain stimulations, vestibular caloric stimulation, epidural motor cortex stimulation, and deep brain stimulation, were effective in some cases/small-sized studies and can be recommended in the management of therapy-resistant PS-TP. Interestingly, the stimulation to other areas, e.g., the motor cortex, periventricular/periaqueductal gray matter, and thalamus/internal capsule, showed more effect than the stimulation to the thalamus alone. Further studies on brain or spinal stimulation are required for evidence.

Idiopathic Parkinson's disease and chronic pain in the era of deep brain stimulation: a systematic review and meta-analysis.

OBJECTIVE: Pain is the most common nonmotor symptom of Parkinson's disease (PD) and is often undertreated. Deep brain stimulation (DBS) effectively mitigates the motor symptoms of this multisystem neurodegenerative disease; however, its therapeutic effect on nonmotor symptoms, especially pain, remains inconclusive. While there is a critical need to help this large PD patient population, guidelines for managing this significant disease burden are absent. Herein, the authors systematically reviewed the literature and conducted a meta-analysis to study the influence of traditional (subthalamic nucleus [STN] and globus pallidus internus [GPi]) DBS on chronic pain in patients with PD. METHODS: The authors performed a systematic review of the literature and a meta-analysis following PRISMA guidelines. Risk of bias was assessed using the levels of evidence established by the Oxford Centre for Evidence-Based Medicine. Inclusion criteria were articles written in English, published in a peer-reviewed scholarly journal, and about studies conducting an intervention for PD-related pain in no fewer than 5 subjects. RESULTS: Twenty-six studies were identified and included in this meta-analysis. Significant interstudy heterogeneity was detected (Cochran's Q test p < 0.05), supporting the use of the random-effects model. The random-effects model estimated the effect size of DBS for the treatment of idiopathic pain as 1.31 (95% CI 0.84-1.79). The DBS-on intervention improved pain scores by 40% as compared to the control state (preoperative baseline or DBS off). CONCLUSIONS: The results indicated that traditional STN and GPi DBS can have a favorable impact on pain control and improve pain scores by 40% from baseline in PD patients experiencing chronic pain. Further trials are needed to identify the subtype of PD patients whose pain benefits from DBS and to identify the mechanisms by which DBS improves pain in PD patients.

Orofacial Pain: Molecular Mechanisms, Diagnosis, and Treatment 2021.

The Special Issue "Orofacial Pain: Molecular Mechanisms, Diagnosis, and Treatment 2021" contains 6 articles published by 41 authors from different countries focusing on nucleus accumbens core GABAergic neurons, receptor-interacting serine/threonine-protein kinase 1, pannexin 1-mediated ATP signaling, ultra-low-frequency transcutaneous electrical nerve stimulation, and triamcinolone acetonide. The content covers several pain models, including neuropathic pain caused by peripheral nerve constriction or malpositioned dental implants, tongue cancer, myogenous temporomandibular dysfunction, and oral ulcerative mucositis. In addition, a review paper on trigeminal neuralgia is included.

An observational study of centrally facilitated pain in individuals with chronic low back pain.

Introduction: Central pain facilitation can hinder recovery in people with chronic low back pain (CLBP). Objectives: The objective of this observational study was to investigate whether indices of centrally facilitated pain are associated with pain outcomes in a hospital-based cohort of individuals with CLBP undertaking a pain management programme. Methods: Participants provided self-report and pain sensitivity data at baseline (n = 97) and again 3 months (n = 87) after a cognitive behavioural therapy-based group intervention including physiotherapy. Indices of centrally facilitated pain were pressure pain detection threshold, temporal summation and conditioned pain modulation at the forearm, Widespread Pain Index (WPI) classified using a body manikin, and a Central Mechanisms Trait (CMT) factor derived from 8 self-reported characteristics of anxiety, depression, neuropathic pain, fatigue, cognitive dysfunction, pain distribution, catastrophizing, and sleep. Pain severity was a composite factor derived from Numerical Rating Scales. Cross-sectional and longitudinal regression models were adjusted for age and sex. Results: Baseline CMT and WPI each was associated with higher pain severity (CMT: r = 0.50, P < 0.001; WPI: r = 0.21, P = 0.04) at baseline and at 3 months (CMT: r = 0.38, P < 0.001; WPI: r = 0.24, P = 0.02). High baseline CMT remained significantly associated with pain at 3 months after additional adjustment for baseline pain (ß = 2.45, P = 0.04, R 2 = 0.25, P < 0.0001). Quantitative sensory testing indices of pain hypersensitivity were not significantly associated with pain outcomes at baseline or at 3 months. Conclusion: Central mechanisms beyond those captured by quantitative sensory testing are associated with poor CLBP outcome and might be targets for improved therapy.

Partial Restoration of Spinal Cord Neural Continuity via Sural Nerve Transplantation Using a Technique of Spinal Cord Fusion.

BACKGROUND: Spinal cord injury (SCI) can cause paralysis and serious chronic morbidity, and there is no effective treatment. Based on our previous experimental results of spinal cord fusion (SCF) in mice, rats, beagles, and monkeys, we developed a surgical protocol of SCF for paraplegic human patients. We designed a novel surgical procedure of SCF, called sural nerve transplantation (SNT), for human patients with lower thoracic SCI and distal cord dysfunction. METHODS: We conducted a clinical trial (ChiCTR2000030788) and performed SNT in 12 fully paraplegic patients due to SCI between T1 and T12. We assessed pre- and postoperative central nerve pain, motor function, sensory function, and autonomic nerve function. Conduction of action potentials across the sural nerve transplant was evaluated. Neural continuity was also examined by diffusion tensor imaging (DTI). RESULTS: Among the 12 paraplegic patients enrolled in this clinical trial, seven patients demonstrated improved autonomic nerve functions. Seven patients had clinically significant relief of their symptoms of cord central pain. One patient, however, developed postoperative cord central pain (VAS: 4). Five patients had varying degrees of recovered sensory and/or motor functions below the single neurologic level 1 month after surgery. One patient showed recovery of electrophysiologic, motor-evoked potentials 6 months after the operation. At 6 months after surgery, DTI indicated fusion and nerve connections of white cord and sural nerves in seven patients. CONCLUSION: SNT was able to fuse the axonal stumps of white cord and sural nerve and at least partially improve the cord central pain in most patients. Although SNT did not restore the spinal cord continuity in white matter in some patients, SNT could restore spinal cord continuity in the cortico-trunco-reticulo-propriospinal pathway, thereby restoring in part some motor and sensory functions. SNT may therefore be a safe, feasible, and effective method to treat paraplegic patients with SCI. Future clinical trials should be performed to optimize the type/technique of nerve transplantation, reduce surgical damage, and minimize postoperative scar formation and adhesion, to avoid postoperative cord central pain. CLINICAL TRIAL REGISTRATION: [http://www.chictr.org.cn/showproj.aspx?proj=50526], identifier [ChiCTR2000030788].

Evolución del dolor en pacientes con sensibilización central y artrosis tras artroplastia de rodilla / Pain evolution in patients with central sensitization and osteoarthritis after knee arthroplasty

Introducción: En pacientes con artrosis de rodilla se ha identificado un 30% de asociación de dolor de sensibilización central (DSC). El objetivo es analizar la persistencia de DSC en pacientes tras artroplastia de rodilla y su correlación con la intensidad del dolor, funcionalidad y los factores determinantes asociados, además de evaluar la exploración física como instrumento de valoración. Material y métodos: Estudio cuasiexperimental antes-después de pacientes intervenidos de artroplastia total de rodilla. Se analiza la evolución de variables subjetivas (características del dolor, cuestionarios painDETECT, WOMAC y escala visual numérica) y de exploración física (hiperalgesia térmica, alodinia, hipoestesia, algometría y goniometría), tres meses antes y tres y seis meses después de la cirugía mediante el test de ANOVA de medidas repetidas para las cuantitativas y el Q de Cochran para las cualitativas. Se utilizó la prueba de Spearman para la correlación de los cuestionarios, del PD-Q y variables de exploración y para el modelo multivariante del PD-Q con determinantes clínicos. Resultados: Sesenta y siete pacientes completaron el estudio. La evolución de las variables cuantitativas y cualitativas fue significativa, con correlación entre cuestionarios. En el modelo multivariante lineal de PD-Q se obtuvo relación significativa de antecedentes de limitación movilidad en flexión, dolor musculoesquelético crónico y la asociación de depresión y tiempo. Conclusiones: Un porcentaje significativo de pacientes con artrosis de rodilla tras artroplastia persistieron con probable DSC, correlacionándose con intensidad y funcionalidad. La limitación de movilidad y comorbilidad crónica previas podrían ser determinantes de DSC, siendo la exploración y anamnesis, herramientas útiles en consulta.(AU)

IntroductionIn patients with knee osteoarthritis, a group of 30% has been identified with central pain sensitization (CPS). The aim is to analyze the persistence of CPS in patients after knee arthroplasty and its correlation with pain intensity, functionality, determining factors and to evaluate physical examination as an assessment instrument.Material and methodsQuasi-experimental before–after study of patients operated on total knee arthroplasty. The evolution of subjective variables (pain characteristics, painDETECT questionnaire, WOMAC and Numerical Rating Scale) and physical examination (thermal hyperalgesia, allodynia, hypoesthesia, algometry and goniometry) 3 months before and 3 and 6 months after surgery are analysed using repeated measures ANOVA test for the quantitative ones and Cochran's Q for the qualitative ones. Spearmen test was used for the correlation of the questionnaires, the PD-Q and exploration variables and for the multivariate model of the PD-Q with clinical determinants. Results: Sixty-seven patients completed the study. The evolution of the quantitative and qualitative variables was significant, with a correlation between questionnaires. In the linear multivariate model of PD-Q, a significant relationship was obtained from personal history of flexion limitation, chronic musculoskeletal pain and the association between depression and time. Conclusions: A significant percentage of patients with knee osteoarthritis after arthroplasty persisted with probable CPS, correlating with intensity and functionality. The limitation of mobility and previous chronic comorbidity could be determinants of CPS, with anamnesis and exploration being useful tools in consultation.(AU)

The effect of one dry needling session on pain, central pain processing, muscle co-contraction and gait characteristics in patients with knee osteoarthritis: a randomized controlled trial.

OBJECTIVES: To assess the immediate and three days postintervention effect of one dry needling session compared to one sham needling session on pain, central pain processing, muscle co-contraction and spatiotemporal parameters during gait in knee osteoarthritis patients. METHODS: A double-blind randomized controlled trial was conducted. Sixty-one knee osteoarthritis patients were randomly assigned to the dry needling or sham needling group. Primary outcomes were pain and central pain processing. Secondary outcomes included muscle co-contraction and spatiotemporal parameters during gait. Patients were assessed at baseline and 15 min after the intervention, and pain also three days after the intervention. Linear mixed models were used to examine between- and within-group differences. RESULTS: No significant between-group differences for pain were found, but within-group scores showed a significant decrease 15 min after sham needling and three days after dry needling. The mean conditioned pain modulation effect measured at the m. Trapezius worsened significantly 15 min after sham needling compared to after dry needling (between-group difference). However, individual conditioned pain modulation percentage scores remained stable over time. Various significant within-group differences were found 15 min after sham needling: a decrease of conditioned pain modulation measured at m. Quadriceps and m. Trapezius and stride- and step-time scores, and an increase in step length and widespread pain pressure threshold. A significant decrease in muscle co-contraction index of the m. Vastus Medialis and Semitendinosus was found as within-group difference 15 min after dry needling. CONCLUSIONS: Dry needling has no larger effect on pain, central pain processing, muscle co-contraction and gait pattern 15 min and three days postintervention compared to sham needling. Mean conditioned pain modulation scores worsened after sham needling compared to after dry needling. Further research remains necessary.