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Neuroimaging studies have documented brain structural alterations induced by chronic pain, particularly in gray matter volume. However, the effects of trigeminal neuralgia (TN), a severe paroxysmal pain disorder, on cortical morphology are not yet known. In this study, we recruited 30 TN patients and 30 age-, and gender-matched healthy controls (HCs). Using Computational Anatomy Toolbox (CAT12), we calculated and compared group differences in cortical thickness, gyrification, and sulcal depth with two-sample t tests (p

Sectio Caesarea is a fragmented tissue or skin that stimulates the sensory area and stimulates the safety of sensory areas, resulting in and other neurological injuries can be a risk of infection if the opening of tissues and lack of treatment cause bacteria to enter through operating wounds. The purpose of the research aims to illustrate the acute nursing care of a post section Caesarea with autogenic relaxation therapy. Methodelogythis research is deductive with a qualitative approach and case study design with acute pain disorders in post section cesarean with autogenic relaxation therapy. The result is maternal screening indicates a scale of 3 pain, acute pain like gangstas, pain scale 3, pain that is felt constantly on the move and is impeded by mobility, activity interrupted. Vital Sign is within normal limits, the action done by performing an autogenic relaxation to treat post pain, after three days of nursing and treatment of the subject data has cooled down on both sides.Keywords: Sectio-Caesarea, nursing care, pain disorder

The present study aimed to investigate mandibular asymmetry as a possible etiopathologic factor in temporomandibular disorder (TMD). A prospective cross-sectional study of patients with dentofacial deformities seeking corrective orthognathic surgery was conducted. The pre-operative prevalence of TMD in patients with mandibular asymmetry and other dentofacial deformities was assessed using the Diagnostic Criteria for TMD (DC/TMD) Axis I protocol. A total of 134 patients were recruited – 82 with mandibular asymmetry and 52 without. There was a significantly higher prevalence of TMD in those with mandibular asymmetry (67.1%; 95% CI 59 to 75%) compared to those without (40.4%; 95% CI 32 to 49%, p = 0.002). The overall pre-operative prevalence of TMD in this population of patients was 56.7% (95% CI 48 to 65%). Pain disorder only was present in 9.7%, TMJ disorder only in 29.9%, and both pain and TMJ disorders in 17.2%. The most prevalent type of TMD is disc displacement with reduction (77.6%), followed by myalgia (35.5%) and arthralgia (21.1%). The prevalence of TMD in those with mandibular asymmetry was significantly higher than those without, suggesting that mandibular asymmetry could be a possible etiopathologic factor in TMD. The significantly higher prevalence of temporomandibular disorder in those with mandibular asymmetry suggests that we need to be especially cognizant of this condition in our pre-operative, surgical, and post-operative management of this group of orthognathic patients.

A dismenorreia primária é considerada um distúrbio álgico em região suprapúbica associada também a outros sintomas, que ocorrem no período menstrual, provocando redução da qualidade das atividades de vida diária, atenuação da produtividade laboral e absenteísmo, constituindo-se um problema de saúde pública, o que torna imprescindível a busca por tratamentos eficientes. Diante dessa problemática e do grande número de mulheres que sofrem e são prejudicadas por esse distúrbio a pergunta norteadora desta pesquisa foi: “Quais as terapias não farmacológicas que podem combater ou amenizar a dismenorreia?” O objetivo deste estudo foi identificar na literatura evidências científicas sobre terapias não farmacológicas que podem ser utilizadas para o alívio da dismenorreia primária. Trata-se de uma revisão integrativa de literatura, que explorou artigos nas bases de dados Literatura Latino-Americana e do Caribe em Ciências da Saúde e Medical Literature Analysis and Retrieval System Online. O corpus da revisão foi composto por 29 publicações. Os métodos não farmacológicos relevantes para a redução da dismenorreia primária encontrados foram: acupressão; acupuntura; aromaterapia; bandagem elástica funcional; estimulação elétrica nervosa transcutânea; exercícios físicos; massagem aromaterapêutica; massagem terapêutica; moxabustão; pilates; raios infravermelhos; termoterapia e yoga. Os estudos apontaram que estes métodos foram efetivos para o alívio da dismenorreia primária. Nesse âmbito, é importante que os profissionais de saúde, tenham conhecimento acerca da efetividade destas terapias, o que contribui para a integralidade do cuidado, orientação eficiente e assertiva quanto aos inúmeros métodos alternativos existentes para estes quadros dolorosos.

Objectives With the International Classification of Diseases 11th revision (classifying fibromyalgia as a primary pain disorder) soon to be implemented, the importance of pain physicians being able to identify patients with fibromyalgia is emphasized. The diagnostic criteria proposed in 2016 are based on self-reported pain distribution and symptom severity. The study aimed to evaluate the diagnostic accuracy of the 2016 diagnostic criteria for fibromyalgia applied in a population of patients with high impact chronic pain referred for pain rehabilitation. Methods The study was performed as a diagnostic accuracy study at two Danish interdisciplinary pain rehabilitation centers, including 215 participants. All participants were evaluated clinically to identify patients with fibromyalgia. The diagnosis was based on expert opinion, but the minimum requirements were: (1) pain in all four body quadrants and axially for at least three months and (2) minimum 8 of 18 positive tender points. Participants filled in the fibromyalgia survey questionnaire, the patient version of the 2016 diagnostic criteria. Sensitivity, specificity, likelihood ratios, and positive and negative post-test probabilities were calculated using a clinical diagnosis of fibromyalgia as the reference standard. Results Based on clinical diagnosis 45% of the participants were diagnosed with fibromyalgia; of these, only 19% had been diagnosed previously. The 2016 diagnostic criteria demonstrated a sensitivity of 88.5%, a specificity of 81.5%, a positive likelihood ratio of 4.79, a negative likelihood ratio of 0.14, a positive post-test probability of 79.4%, and a negative post-test probability of 10.2%. Conclusions Fibromyalgia was severely under-diagnosed among patients with high impact chronic pain referred to tertiary care in two pain rehabilitation centers in Denmark. The 2016 diagnostic criteria showed sufficient discriminatory properties suggesting that the fibromyalgia survey questionnaire can be used as a screening tool assisting the identification of fibromyalgia in this patient population.

Study Objectives It is common to provide insomnia patients a second treatment when the initial treatment fails, but little is known about optimal treatment sequences for different patient types. This study examined whether pre-treatment characteristics/traits predict optimal treatment sequences for insomnia patients. Methods A community sample of 211 adults (132 women; Mage = 45.6 ± 14.9 years) with insomnia were recruited. Patients were first treated with behavioral therapy (BT) or zolpidem (Zol). Non-remitting BT recipients were randomized to a second treatment with either Zol or cognitive therapy; non-remitting Zol recipients underwent BT or Trazodone as a second treatment. Remission rates were assessed at the end of the first and second 6-week treatments. We then compared the remission rates of dichotomous groups formed on the basis of gender, age, pretreatment scores on SF36 and Multidimensional Fatigue Scale, the presence/absence of psychiatric/medical comorbidities or pain disorders, and mean subjective sleep duration and efficiency within and across treatment sequences. Results Lower remission rates were noted for those: with a pain disorder, poor mental health perceptions, high MFI fatigue scores, and lower sleep times and efficiencies. Patients with a pain disorder responded best to the BT-to-Zol sequence, whereas patients with more mental impairment, severe fatigue, short sleep, and low sleep efficiency responded poorly to treatment starting with BT. Conclusions Pain, fatigue, poor mental health status, and subjective sleep duration and efficiency all affect response to different insomnia treatment sequences. Findings may guide clinicians in matching insomnia treatments to their patients. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT01651442, Protocol version 4, April 20, 2011, registered June 26, 2012, https://clinicaltrials.gov/ct2/show/NCT01651442?rslt=With&type=Intr&cond=Insomnia&cntry=US&state=US%3ACO&city=Denver&age=12&draw=2&rank=1.

Despite the ubiquity of rib fractures in patients with blunt chest trauma, long-term outcomes for patients with this injury pattern are not well described.The Functional Outcomes and Recovery after Trauma Emergencies (FORTE) project has established a multicenter prospective registry with 6- to 12-month follow-up for trauma patients treated at participating centers. We combined the FORTE registry with a detailed retrospective chart review investigating admission variables and injury characteristics. All trauma survivors with complete FORTE data and isolated chest trauma (Abbreviated Injury Scale score of ≤1 in all other regions) with rib fractures were included. Outcomes included chronic pain, limitation in activities of daily living, physical limitations, exercise limitations, return to work, and both inpatient and discharge pain control modalities. Multivariable logistic regression models were built for each outcome using clinically relevant demographic and injury characteristic univariate predictors.We identified 279 patients with isolated rib fractures. The median age of the cohort was 68 years (interquartile range, 56-78 years), 59% were male, and 84% were White. Functional and quality of life limitations were common among survivors of isolated rib fractures even 6 to 12 months after injury. Forty-three percent of patients without a preexisting pain disorder reported new daily pain, and new chronic pain was associated with low resilience. Limitations in physical functioning and exercise capacity were reported in 56% and 51% of patients, respectively. Of those working preinjury, 28% had not returned to work. New limitations in activities of daily living were reported in 29% of patients older than 65 years. Older age, higher number of rib fractures, and intensive care unit admission were independently associated with higher odds of receiving regional anesthesia. Receiving a regional nerve block did not have a statistically significant association with any patient-reported outcome measures.Isolated rib fractures are a nontrivial trauma burden associated with functional impairment and chronic pain even 6 to 12 months after injury.Prognostic/epidemiologic, level III.

International audience; BACKGROUND: Parents of children with atopic dermatitis (AD) report reduced quality of life and higher stress level, which could increase risk of psychiatric and pain disorders, and medication use. METHODS: By use of Danish national registries, we identified family members of all first-born Danish children born between January 1(st) , 1995 and December 31(st) , 2013 with a hospital diagnosis of AD, matched them 1:10 with family members of children without AD, and followed the cohorts over time. RESULTS: Mothers of children with hospital-managed AD had higher risk of filling a prescription for medications for depression, anxiety, pain and sleep problems, and of consulting a psychologist, but most associations disappeared after full adjustment. Siblings had higher risk of receiving a diagnosis for adjustment disorder, and fathers showed increased risk of filling a prescription for pain medication and of divorce, in crude but not adjusted models. CONCLUSIONS: The increased risk of study endpoints seen in mothers of children with hospital-managed AD was not explained by pediatric AD alone. Rather, the total burden in these families including parent and child morbidity and socioeconomic resources seem to explain these observations. The burden in families of children with AD may potentially affect the overall management of their child’s AD.

Background Somatoform disorder (SD), known as the presence of physical symptoms suggesting a physical condition, for which there are no demonstrable organic findings or established physiological mechanisms with positive evidence that the symptoms are related to psychological causes. The aim of this study was to highlight the epidemiological characteristics, demographic features, comorbidities, and clinical presentations of patients with SD. Materials and methods This was a retrospective study of SD patients at King Abdulaziz Medical City in Riyadh, Saudi Arabia. We reviewed the patients' electronic health records from January 2015 to December 2020 for collecting the patients' demographic information, including gender, age, marital status, and occupation. The types of SD, presenting symptoms of each disorder, department to which patients initially presented, comorbidities, and management were also documented. The diagnosis of SD was based on the International Classification of Diseases, Tenth Revision (ICD-10). Results In total, 89 patients were included in the study. The majority (n=50, 56.2%) were female, with a mean age of 42.7±17.1 years. More than half of the sample was married (n=54, 60.7%). The most common subtype of SD was somatization disorder followed by conversion disorder, pain disorder, and hypochondriasis, diagnosed in 69 (77.5%), 12 (13.5%), 5 (5.6%), and three (3.4%) patients, respectively. Neurological symptoms and pain were the most frequent presenting symptoms for all the somatoform patients. More than half of the sample (n=48, 53.9%) initially presented at an outpatient clinic. Conclusions The number of SD patients was less than expected, and a third did not receive any treatment. This emphasizes the need for more SD awareness among clinicians in various medical specialties. Appropriate SD and other mental disorders education for physicians may support achieving a better identification of SD and subsequently an improved quality of life for the patients.

Background: Musculoskeletal pain (MSKP) is an extremely common pain disorder in almost all populations. Self-management (SM) support is a programme to prepare people to self-manage their health condition effectively, while maintaining quality of life. SM is a cost-effective and context-specific strategy to address the global public health burden. Objectives: Self-management needs a change in behaviour from seeking unnecessary medical care to safely self-managing symptoms. As changing individuals’ behaviour is challenging, the objective of my literature review was to identify the characteristics, in both therapist and patient, to successfully engage in SM. Method: A narrative literature review, that could inform evidence-based support programmes for SM of MSKP. Results: Studies on successful implementation of SM of MSKP do not report strong outcomes. However, in more recent years a few positive outcomes were reported, possibly as a result of research evidence for the application of psychosocial skills and contemporary pain neuroscience in the management of persistent MSKP. Conclusion: Psychologically-informed physiotherapy, addressing psychosocial barriers to the maintenance of SM programmes, could facilitate more successful outcomes. Clinical implications: Before engaging in a SM support programme, obstacles to behaviour change must be identified and addressed in a SM support programme, to facilitate individuals towards taking safe responsibility for their healthcare. Therapists working with patients with persistent MSKP, should upskill themselves to be in line with the latest pain and psychosocial research literature. Moreover, communication skills training seems to be a priority for effective SM support programmes.

Insertion tendinosis of stylomandibular ligament (SML) or Ernest syndrome is a very rare and under reported head and neck pain disorder. The pain originates from the insertion of stylomandibular region and radiates to the temple, lateral side of the neck and temporomandibular joint (TMJ). The diagnosis is confirmed by palpation of SML and local anesthetic block at the insertion of SML. The authors report 4 patients who presented with chronic pain which radiated to the TMJ and temple and did not respond to conservative management. All patients after diagnosed with Local anesthetic block were given methylprednisolone injection at the insertion of SML. Complete remission of pain was seen at 12 months of follow up without any recurrence. Craniofacial surgeons involved in the treatment of various head and neck pain should include this less documented syndrome in their differential diagnosis when treating TMJ disorders.

Background Low back pain secondary to discopathy is a common pain disorder. Multiple minimally invasive therapeutic modalities have been proposed; however, to date no study has compared percutaneous laser disc decompression (PLDD) with intradiscal injection of radiopaque gelified ethanol (DiscoGel®). We are introducing the first study on patient-reported outcomes of DiscoGel® vs. PLDD for radiculopathy. Methods Seventy-two patients were randomly selected from either a previous strategy of PLDD or DiscoGel®, which had been performed in our center during 2016-2017. Participants were asked about their numeric rating scale (NRS) scores, Oswestry disability index (ODI) scores, and progression to secondary treatment. Results The mean NRS scores in the total cohort before intervention was 8.0, and was reduced to 4.3 in the DiscoGel® group and 4.2 in the PLDD group after 12 months, which was statistically significant. The mean ODI score before intervention was 81.25% which was reduced to 41.14% in the DiscoGel® group and 52.86% in the PLDD group after 12 months, which was statistically significant. Between-group comparison of NRS scores after two follow-ups were not statistically different (P = 0.62) but the ODI score in DiscoGel® was statistically lower (P = 0.001). Six cases (16.67%) from each group reported undergoing surgery after the follow-up period which was not statistically different. Conclusions Both techniques were equivalent in pain reduction but DiscoGel® had a greater effect on decreasing disability after 12 months, although the rate of progression to secondary treatments and/or surgery was almost equal in the two groups.

Rheumatic diseases are a leading cause of chronic, noncancer pain. Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease characterized by periodic flares that can result in irreversible target organ damage, including end-stage renal disease. Both intermittent and chronic musculoskeletal pain, as well as fibromyalgia (considered a centralized pain disorder due to dysregulation of pain processing in the central nervous system), are common in SLE. Opioids are generally not indicated for long-term management of musculoskeletal pain or centralized pain (fibromyalgia) because of lack of efficacy, safety issues ranging from adverse medical effects to overdose, and risk for addiction (1,2). In this study of 462 patients with SLE from the population-based Michigan Lupus Epidemiology and Surveillance (MILES) Cohort and 192 frequency-matched persons without SLE, nearly one third (31%) of SLE patients were using prescription opioids during the study period (2014-2015), compared with 8% of persons without SLE (p0.001). Among the SLE patients using opioids, 97 (68%) were using them for1 year, and 31 (22%) were concomitantly on two or more opioid medications. Among SLE patients, those using the emergency department (ED) were approximately twice as likely to use prescription opioids (odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3-3.6; p = 0.004). In SLE, the combined contributions of underlying disease and adverse effects of immunosuppressive and glucocorticoid therapies already put patients at higher risk for some known adverse effects attributed to long-term opioid use. Addressing the widespread and long-term use of opioid therapy in SLE will require strategies aimed at preventing opioid initiation, tapering and discontinuation of opioids among patients who are not achieving treatment goals of reduced pain and increased function, and consideration of nonopioid pain management strategies.

Fibromyalgia syndrome (FMS) is a chronic pain syndrome. Neuroimaging studies provided evidence of altered gray matter volume (GMV) in FMS but, similarly, in chronic pain of other origin as well. Therefore, the purpose of this study was to evaluate the disease specificity of GMV alterations in FMS by direct comparison. Structural MRI data of the brain were acquired in 25 females with FMS and two different control groups: 21 healthy subjects and 23 patients with osteoarthritis. Regional GMVs were compared by voxel-based morphometry and additional ROI-analyses. In conclusion, we did not identify significant GMV alterations in either FMS or OA patients compared to healthy controls when adopting a conservative statistical approach with multiple comparison correction. However, even under a more liberal approach no FMS-specific GMV changes were found because both pain groups presented increased gray matter volumes in the precentral gyrus and decreased GMV in the angular gyrus/middle occipital gyrus and middle temporal gyrus in comparison with healthy controls. Since no differences between both pain groups could be detected cortical GMV changes in FMS should not be interpreted as FMS-specific but might rather reflect changes in chronic pain in general. This previously held notion is confirmed in this study by direct comparison with a control group consisting of another pain disorder.

Francis Sahngun Nahm,1,2 Sang-Soep Nahm,3 Woong Ki Han,1 Ho Young Gil,4 Eunjoo Choi,1 Pyung Bok Lee1,2 1Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea; 2College of Medicine, Seoul National University, Seoul, South Korea; 3Laboratory of Veterinary Anatomy, College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 4Department of Anesthesiology and Pain Medicine, Ajou University Hospital, Suwon, South Korea Purpose: Complex regional pain syndrome (CRPS) is a rare but refractory pain disorder. Recent advanced information retrieval studies using text-mining and network analysis have suggested nuclear factor kappa B (NFκB) as a possible central mediator of CRPS. The brain is also known to play important roles in CRPS. The aim of this study was to evaluate changes in cerebral NFκB in rats with CRPS. Materials and methods: The chronic post-ischemia perfusion (CPIP) model was used as the CRPS animal model. O-rings were applied to the left hind paws of the rats. The rats were categorized into three groups according to the results of behavioral tests: the CPIP-positive (A) group, the CPIP-negative (B) group, and the control (C) group. Three weeks after the CPIP procedure, the right cerebrums of the animals were harvested to measure NFkB levels using an ELISA. Results: Animals in group A had significantly decreased mechanical pain thresholds (P

Objective To assess the intraepidermal nerve fiber density in patients diagnosed with fibromyalgia (FM) and to evaluate the role of IgM binding to trisulfated heparin disaccharide (TS-HDS) in these patients. Methods FM is a poorly understood pain disorder with several proposed pathophysiologic mechanisms. It is characterized by widespread pain, fatigue, and sleep abnormalities. Small fiber neuropathy (SFN) has been proposed as an underlying mechanism, and patients with FM have been shown to have a reduction in the intraepidermal nerve fiber density. An underlying inflammatory process that could be a result of autoimmune phenomena has also been suggested. Non-length-dependent SFN (NLDSFN) has been shown to have a higher incidence of autoimmune disease. Twenty-two patients with established diagnosis of FM underwent skin biopsy at 2 sites; 10 cm above the lateral malleolus and 10 cm above the patella. Serum IgM binding to TS-HDS was assayed using an ELISA method. Results A total of 5/22 patients had positive TS-HDS antibodies; of these, 4 had NLDSFN (P = 0.0393). Comparison with a control group at Washington University showed no significant difference in percentage with TS-HDS antibodies (P = 0.41). When compared with Washington University database of skin biopsy, there was a trend for an increased percentage of NLDSFN in patients with FM (P = 0.06). Conclusions This study further supports the hypothesis that a subgroup of patients with FM has SFN. We suggest a correlation between the presence of NLDSFN and TS-HDS antibodies.

Purpose Persistent idiopathic facial pain (PIFP) is a poorly defined and debilitating chronic pain state with a challenging and often inadequate treatment course. This is the first case report identifying the novel use of low-dose lumbar intrathecal ziconotide to successfully treat PIFP with nearly complete resolution of pain and minimal to no side effects. Methods The patient was a 37 year-old female whose PIFP was refractory to multimodal medication management and multiple neurovascular surgical interventions. A single-shot lumbar intrathecal trial of ziconotide (2.5 mL, equivalent 2.5 μg) was injected when she was at her baseline pain level - VAS 7/10. She received complete resolution of her pain for about 9 hours, concordant with ziconotide's half-life. She was subsequently implanted with a lumbar intrathecal delivery system. Results The patient experienced complete resolution of her facial pain with a single-shot intrathecal trial of ziconotide. The intrathecal pump system has provided nearly complete (VAS 1/10) pain relief. Two flares of pain occurred 10 and 18 months after pump placement, which subsequently resolved after increasing the ziconotide dose by 0.5 μg/day on each occasion. The patient is currently maintained on a dose of 2.0 μg/day and is pain-free. Conclusion This is the first case report describing the use of a single-shot lumbar intrathecal trial of ziconotide and subsequent placement of lumbar (as opposed to thoracic) intrathecal ziconotide pump for PIFP. A single-injection intrathecal trial is a low-risk, viable option for patients with this debilitating and frustrating pain condition. Successful trials and subsequent intrathecal pump placement with ziconotide may supplant multimodal medication management and/or invasive orofacial surgical intervention for PIFP.

Fibromyalgia syndrome (FMS) is a pain disorder characterized by chronic widespread pain, fatigue, and sleep disturbance, in the absence of any well-defined underlying organic disease. The exact pathophysiology and the mechanism which links different factors related to the disease is still unknown. Due to unknown precise pathogenesis, the coexistence of other diseases, and overlapping clinical features, FMS diagnosis may be laborious. Various treatment strategies are used, only a few Food and Drug Administration (FDA) approved, still we are facing challenges regarding effective treatment. Recently, medicinal cannabis has proven to be effective in chronic pain conditions such as osteoarthritis, neuropathic pain, and other non-cancer chronic pain. However, further research is needed about how the cannabinoid system works with the pain pathway. Using the fact that medicinal cannabis is effective in the treatment of chronic pain and certain rheumatic diseases, in this review, we aim to analyze the role of the cannabinoid system in fibromyalgia syndrome. We followed Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines in searching PubMed, MEDLINE (through PubMed), PubMed Central, and Google Scholar using keywords "fibromyalgia, chronic pain, cannabis, cannabinoids, pharmacotherapy, alternative therapy" and Medical Subject Heading (MeSH) words. After applying inclusion/exclusion criteria and checking for the quality assessment, 22 articles were retrieved and used for the analysis of the role of cannabis in the treatment of fibromyalgia. The two main compounds of cannabis with analgesic and anti-inflammatory properties are cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), and their ratio determines the effect on various symptoms of FMS. We included studies regarding the use of cannabinoids in the treatment of fibromyalgia, investigating the use of nabilone, dronabinol (a synthetic analog of THC), Bedrocan (22.4 mg THC

Hypnotizability, one’s ability to experience cognitive, emotional, behavioral, and physical changes in response to suggestions in the context of hypnosis, is a highly stable trait associated with increased functional connectivity between the left dorsolateral prefrontal cortex (L-DLPFC) and dorsal anterior cingulate cortex (dACC). We conducted a preregistered, triple-blinded, randomized controlled trial to test the ability of continuous theta-burst stimulation (cTBS) over a personalized neuroimaging-based L-DLPFC target to temporarily enhance hypnotizability. We tested our hypothesis in 78 patients with fibromyalgia syndrome (FMS), a functional pain disorder for which hypnosis has consistently been shown to be beneficial as a nonpharmacological treatment option. Pre-to-post cTBS change in Hypnotic Induction Profile scores (HIP; a standardized measure of hypnotizability) was significantly greater in the Active versus Sham group. Our findings suggest a causal relationship between L-DLPFC and dACC function and hypnotizability. Dose-response optimization should be further examined to formalize guidelines for future clinical utilization.Trial registrationClinicalTrials.govNCT02969707

Chronic pain is an unpleasant sensory and emotional experience that persists or recurs more than three months and may extend beyond the expected time of healing. Recently, nociplastic pain has been introduced as a descriptor of the mechanism of pain, which is due to the disturbance of neural processing without actual or potential tissue damage, appearing to replace a concept of psychogenic pain. An interdisciplinary task force of the International Association for the Study of Pain (IASP) compiled a systematic classification of clinical conditions associated with chronic pain, which was published in 2018 and will officially come into effect in 2022 in the 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) by the World Health Organization. ICD-11 offers the option for recording the presence of psychological or social factors in chronic pain; however, cognitive, emotional, and social dimensions in the pathogenesis of chronic pain are missing. Earlier pain disorder was defined as a condition with chronic pain associated with psychological factors, but it was replaced with somatic symptom disorder with predominant pain in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in 2013. Recently clinical nosology is trending toward highlighting neurological pathology of chronic pain, discounting psychological or social factors in the pathogenesis of pain. This review article discusses components of the pain pathway, the component-based mechanisms of pain, central and peripheral sensitization, roles of chronic inflammation, and the involvement of tryptophan-kynurenine pathway metabolites, exploring the participation of psychosocial and behavioral factors in central sensitization of diseases progressing into the development of chronic pain, comorbid diseases that commonly present a symptom of chronic pain, and psychiatric disorders that manifest chronic pain without obvious actual or potential tissue damage.

Introduction: Hemiplegic shoulder pain (HSP) is the most common pain disorder after stroke with incidence estimates of 30–70% and associated with reductions in function, interference with rehabilitation, and a reduced quality of life. Onset may occur as soon as a week after stroke in 17% of patients. Management of HSP represents a complex treatment pathway with a lack of evidence to support one treatment. The pain has heterogeneous causes. In the acute setting, decreased range of motion in the shoulder can be due to early-onset spasticity, capsular pattern stiffness, glenohumeral pathology, or complex regional pain syndrome (CRPS). As contracture can form in up to 50% of patients after stroke, effective management of the painful shoulder and upper limb with decreased range of motion requires assessment of each possible contributor for effective treatment. The anesthetic diagnostic nerve block (DNB) is known to differentiate spasticity from contracture and other disorders of immobility and can be useful in determining an appropriate treatment pathway.Objective: To create a diagnostic algorithm to differentiate between the causes of HSP in the stiff, painful shoulder in the subacute setting using diagnostic techniques including the Budapest Criteria for CRPS and DNB for spasticity and pain generators.Results: Examination of each joint in the upper extremity with HSP may differentiate each diagnosis with the use of an algorithm. Pain and stiffness isolated to the shoulder may be differentiated as primary shoulder pathology; sensory suprascapular DNB or intra-articular/subacromial injection can assist in differentiating adhesive capsulitis, arthritis, or rotator cuff injury. CRPS may affect the shoulder, elbow, wrist, and hand and can be evaluated with the Budapest Criteria. Spasticity can be differentiated with the use of motor DNB. A combination of these disorders may cause HSP, and the proposed treatment algorithm may offer assistance in selecting a systematic treatment pathway.

Background Alcohol has dual effects on many systems, including the pain system. We will test whether and how chronic alcohol consumption enhances pain sensation to develop pain disorder. Methods We conducted a retrospective matched cohort study using data from the National Health Insurance Research Database (NHIRD) in Taiwan, in patients with and without alcohol use disorder (AUD). This study enrolled 19,174 individuals with AUD as study cohort and 19,174 propensity score-matched individuals without AUD as comparison cohort. The outcome was the incidence of pain disorders and the need for analgesics. The hazard ratios of pain disorders and the need for analgesics were evaluated using Cox proportional hazard regression analysis after adjusting for age, sex, index year, comorbidities, urbanization, areas of residence, and insurance premium. Results The 14 years of follow-up showed that AUD patients had a higher adjusted hazard ratio (aHR) for developing pain disorders than in non-AUD controls [aHR= 1.290, 95% confidence interval (CI): 1.045-1.591]. Besides, AUD patients had a higher risk of analgesic use (aHR = 1.081, 95% CI: 1.064-1.312), including opioids and non-opioid analgesics. Most importantly, AUD patients required more days of analgesic use, increased dose of analgesics, and higher costs of analgesics. Moreover, AUD patients had more anemia (aHR=2.772, 95% CI: 2.581-2.872), which could be a mediating factor. Conclusions AUD patients had higher risks of developing pain disorders and subsequently increased analgesic demand. These results suggest that AUD worsened pain, and pain syndrome is correlated with the duration of chronic alcohol exposure.

Trigeminal neuropathic pain is the most debilitating pain disorder but current treatments including opiates are not effective. A common symptom of trigeminal neuropathic pain is cold allodynia/hyperalgesia or cold hypersensitivity in orofacial area, a region where exposure to cooling temperatures are inevitable in daily life. Mechanisms underlying trigeminal neuropathic pain manifested with cold hypersensitivity are not fully understood. In this study, we investigated trigeminal neuropathic pain in male rats following infraorbital nerve chronic constrictive injury (ION-CCI). Assessed by the orofacial operant behavioral test, ION-CCI animals displayed orofacial cold hypersensitivity. The cold hypersensitivity was associated with the hyperexcitability of small-sized trigeminal ganglion (TG) neurons that innervated orofacial regions. Furthermore, ION-CCI resulted in a reduction of A-type voltage-gated K+currents (IA currents) in these TG neurons. We further showed that these small-sized TG neurons expressed Kv4.3 voltage-gated K+channels, and Kv4.3 expression in these cells was significantly downregulated following ION-CCI. Pharmacological inhibition of Kv4.3 channels with phrixotoxin-2 inhibited IA-currents in these TG neurons and induced orofacial cold hypersensitivity. On the other hand, pharmacological potentiation of Kv4.3 channels amplified IA currents in these TG neurons and alleviated orofacial cold hypersensitivity in ION-CCI rats. Collectively, Kv4.3 downregulation in nociceptive trigeminal afferent fibers may contribute to peripheral cold hypersensitivity following trigeminal nerve injury, and Kv4.3 activators may be clinically useful to alleviate trigeminal neuropathic pain.SIGNIFICANCE STATEMENTTrigeminal neuropathic pain, the most debilitating pain disorder, is often triggered and exacerbated by cooling temperatures. Here, we created infraorbital nerve chronic constrictive injury (ION-CCI) in rats, an animal model of trigeminal neuropathic pain to show that dysfunction of Kv4.3 voltage-gated K+channels in nociceptive-like trigeminal ganglion (TG) neurons underlies the trigeminal neuropathic pain manifested with cold hypersensitivity in orofacial regions. Furthermore, we demonstrate that pharmacological potentiation of Kv4.3 channels can alleviate orofacial cold hypersensitivity in ION-CCI rats. Our results may have clinical implications in trigeminal neuropathic pain in human patients, and Kv4.3 channels may be an effective therapeutic target for this devastating pain disorder.

Background Headache is the most common pain disorder, affecting around 66% of the global population. This study aimed to investigate the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) in treating patients with primary chronic daily headaches (chronic tension-type headache and chronic migraine). Methods Twenty-seven patients participated in the study, divided into 2 groups: a study group (16 patients) and a control group (11 patients). Treatment consisted of 12 high-frequency (5 Hz) real rTMS sessions, delivered over the left dorsolateral prefrontal cortex (DLPFC), whereas sham rTMS was used for the control group. Results Patients of the study group, after real rTMS stimulation, showed a high statistically significant reduction of the measured headache parameters compared to the control group (P value < 0.001), and the percentage of improvement was 94.5%. No significant reduction of headache parameters, after sham rTMS stimulation, was observed in the control group (P value > 0.05) and the percentage of improvement was 7.9%. Conclusion High-frequency rTMS is effective in reducing chronic tension headaches and chronic migraines. This finding runs with the approval of the suggested role of DLPFC in pain control. This might open opinions for new treatment strategies in tension-type headache and migraine prevention.

Early during treatment of an upper extremity injury, the surgeon must be proactive to evaluate the psychological effects of trauma, which have a high likelihood of resulting in depression, anxiety, and post-traumatic stress disorder (PTSD). Taking a moment to ask relevant screening questions can result in expedient treatment. Not recognizing such disorders can result in ineffective motivation for rehabilitation and decreased functional outcome following even the most effortful of reconstructions – which impairs social interaction and ability to return to work. For a variety of reasons, patients also have a propensity for developing chronic opioid reliance. Due to the staggering rates of opioid abuse in the United States, the clinician should keep a vigilant eye out for opioid use that extends more than one month postoperatively and help guide such patients to appropriate therapy and resources to prevent long-term abuse.

Atypical odontalgia is a pain disorder featured by constant pain without any obvious dental pathology. We report a 38-year-old man having chronic orofacial pain in the past two years. The pain was first located in the left maxillary premolar-molar region, but spread to the contra lateral mandible, occipital region, head and shoulders over time. The pain was described as dull and continuous with the intensity of #6 (VAS), and not relieved even after root canal therapy of all teeth and extraction of wisdom teeth . Some comorbid conditions such as TMJ problems and involvement of masticatory muscles were also reported. Finally, the diagnosis of atypical odontalgia was established due to lack of evidence for any organic pathology on clinical and paraclinical investigations, and a combination therapy including fluoxetine and clonazepam was started. Dental practitioners should consider AO when confronting toothache without any reasonable organic cause and avoid unnecessary dental procedures. KEYWORDS Atypical toothache; Malpractice; Endodontics.

Fibromyalgia is generally considered a pain disorder, but most patients have additional symptoms, most commonly fatigue, insomnia and dizziness. Chronic fatigue syndrome and fibromyalgia overlap in symptoms and are associated with a variety of psychophysiological disorders, including depression, anxiety and migraine. Patients with fibromyalgia have central sensitization to pain which can be traced to several factors including genetic variants, prior exposure to pain and stressful life events. Although many people believe that chronic fatigue syndrome is caused by a viral infection, post-viral activation of the immune system or primary immune system dysfunction, to date there is no convincing evidence for any of these disease mechanisms. Large outbreaks of chronic fatigue syndrome in the UK and USA had features consistent with mass psychogenic illness, including a marked female predominance and the lack of objective neurological and laboratory findings.

Background: Myofascial pain syndrome (MPS) is a chronic systemic pain disorder. Among the common treatments, moxibustion has an irreplaceable therapeutic effect and is an effective Traditional Chinese Medicine therapy for MPS. However, the lack of clinical practice guidelines (CPGs) has prompted the publication of guidelines on the use of moxibustion in the treatment of MPS. Methods: The clinical practice guideline will base on the Institute of Medicine, the World Health Organization guideline handbook, the Grade of Recommendations Assessment, Development, and Evaluation the Appraisal of Guidelines for Research & Evaluation II, Reporting Items for practice, Guideline in Healthcare and recommendations thereof will be made on the basis of systematic reviews. We will establish a guidelines development team that will draft clinical questions in the form of population, intervention, comparison, results and conduct a literature search and quality of evidence assessment. The experts will make recommendations after 2 or 3 rounds of Delphi investigations. We will carefully consider the patient's values and preferences and conduct a peer review. Ethics and dissemination: The guidelines will not contain any personal data and will not prejudice individual rights, so no ethical approval will be required. The guidelines will be subject to rigorous peer review and may be published in a journal or circulated at relevant conferences. Results: The guidelines will be published in relevant peer-reviewed journals. Conclusion: This guideline will make it easier for clinicians to treat MPs in the clinical setting and improve the effectiveness of treatment for MPS. Study registration: The study is registered with the International Practice Guideline Registry Platform (IPGRP): IPGRP-2020CN030

Complex regional pain syndrome (CRPS)-an extremely painful primary pain disorder related to trauma-is rare in the orofacial region. The authors describe a case of orofacial CRPS with a clinical phenotype that fits the Budapest diagnostic criteria. A 39-year-old female patient presented with left-side facial pain that had been untreated for 10 months. Symptoms included burning pain and allodynia accompanied by swelling and redness on exposure to cold or stress. The diagnosis was confirmed after stellate ganglion anesthetic block resulted in substantial improvement.

Non-invasive measures of neuroinflammatory processes in humans could substantially aid diagnosis and therapeutic development for many disorders, including chronic pain. Several proton Magnetic Resonance Spectroscopy ((1)H-MRS) metabolites have been linked with glial activity (i.e. choline and myo-inositol) and found to be altered in chronic pain patients, but their role in the neuroinflammatory cascade is not well known. Our multimodal study evaluated resting fMRI connectivity and (1)H-MRS metabolite concentration in insula cortex in 43 patients suffering from fibromyalgia, a chronic centralized pain disorder previously demonstrated to include a neuroinflammatory component, and 16 healthy controls. Patients demonstrated elevated choline (but not myo-inositol) in anterior insula (p=0.03), with greater choline levels linked with worse pain interference (r=0.41, p=0.01). In addition, reduced resting functional connectivity between anterior insula and putamen was associated with both pain interference (whole brain analysis, p(corrected)

Chronic pain is highly prevalent and poorly controlled, of which the accurate underlying mechanisms need be further elucidated. Herbal drugs have been widely used for controlling various pain disorders. The systematic integration of pain herbal data resources might be promising to help investigate the molecular mechanisms of pain phenotypes. Here, we integrated large-scale bibliographic literatures and well-established data sources to obtain high-quality pain relevant herbal data (i.e. 426 pain related herbs with their targets). We used machine learning method to identify three distinct herb categories with their specific indications of symptoms, targets and enriched pathways, which were characterized by the efficacy of treatment to the chronic cough related neuropathic pain, the reproduction and autoimmune related pain, and the cancer pain, respectively. We further detected the novel pathophysiological mechanisms of the pain subtypes by network medicine approach to evaluate the interactions between herb targets and the pain disease modules. This work increased the understanding of the underlying molecular mechanisms of pain subtypes that herbal drugs are participating and with the ultimate aim of developing novel personalized drugs for pain disorders.

Background and Aims Fibromyalgia Syndrome (FMS) is a chronic centralized pain disorder characterized by widespread pain and fatigue. Of those affected by FMS, the majority are women, and minimal research exists involving men. The purpose of this paper is to describe the pain and fatigue experiences of men with FMS from two Western countries, Spain and the United States, in order to support more accurate and earlier recognition and diagnosis in men. Design and Methods We used individual and focus group interviews with qualitative and quantitative assessments. Settings and Participants/Subjects Ten men in Spain and seven men in the United States provided information about their symptoms, psychosocial and health-seeking behaviors, and gender experiences with FMS. Results Men articulated types, trends, and triggers of pain and fatigue that enrich an understanding of their symptoms. For example, men report more localized pain than generalized pain. Employment status and activities, among other contextual factors, impacted men's pain and fatigue experiences. Conclusions Men experience distinct facets of pain and fatigue compared with women, with notable similarities and differences across the Spanish and U.S. samples. Cross-cultural comparisons highlight contextual factors that may inspire future inquiries about determinants of men's experiences with FMS. Clinical Implications The present study could be useful for anyone treating men suffering from FMS, especially care providers in nursing, medical, and psychology fields. These initial findings may prompt a closer examination of recommendations for assessment and diagnostic criteria used internationally for patients with FMS with better recognition of men's experience.

Migraine is a pain disorder accompanied by various symptoms. The insula, a “cortical hub,” is involved in many functions. Few studies have focused on the insula in migraine. We explored the resting-state functional connectivity between the insula and other brain areas in rats subjected to repeated meningeal nociception which was commonly used as animal model of migraine. Inflammatory soup was infused through supradural catheters in conscious rats. The rats were subdivided based on the frequency of the inflammatory soup infusions. Magnetic resonance imaging data were acquired on rats 21 days after inflammatory soup infusion and functional connectivity seeded on the insula was analyzed. In the low-frequency inflammatory soup group, magnetic resonance imaging was performed again 1 h after the glyceryl trinitrate injection following baseline scanning. The cerebellum showed increased functional connectivity with the insula in the inflammatory soup groups. The insula showed increased functional connectivity with the medulla and thalamus in the ictal period in the low-frequency inflammatory soup rats. In the high-frequency inflammatory soup group, several areas showed increased functional connectivity with the insula, including the pons, midbrain, thalamus, temporal association cortex, and retrosplenial, visual, and sensory cortices. Our findings support the hypothesis that the headache phase of migraine depends on the activation and sensitization of the trigeminovascular system, and that the chronification of migraine may be related to higher brain centers and limbic cortices. The insula may be a new target for treatment of migraine.

Importance: Although attachment is associated with sensory modulation among children and adolescents and insecure attachment is associated with pain severity among adolescents, relationships among sensory modulation, attachment, and function have not previously been demonstrated in a clinical sample of children and adolescents with complex persistent pain. Objective: To investigate relationships among sensory modulation, attachment, function, and quality of life (QOL) in a pediatric population with persistent pain. Design: Cross-sectional quantitative design. From October 2015 to July 2017, all children, adolescents, and parents attending a clinic for assessment completed questionnaires and were provided information and consent forms. Those who consented completed sensory modulation and attachment questionnaires. Setting: Tertiary pain management clinic. Participants: Children (ages 8–12 yr) and adolescents (ages 13–18 yr) with persistent pain (pain of >3 mo duration or a specific pain disorder) and the capacity to answer questionnaires independently. Measures: Standardized sensory modulation, attachment, pain intensity, functional disability, and QOL questionnaires. Hypotheses were generated before data collection. Results: Of 152 children and adolescents, 114 children (30 girls, 9 boys) and adolescents (68 girls, 7 boys) met study criteria and consented to participate. Hierarchical multiple regression analyses revealed that sensory sensitivity predicted disability for children and adolescents, and attachment anxiety mediated the relationship between low registration and poorer school-related QOL. Conclusion and Relevance: Behaviors related to insecure attachment patterns provide a mediating pathway from sensory modulation to functional disability; addressing such behaviors clinically may facilitate engagement in daily activities for children and adolescents with persistent pain. What This Article Adds: Results support the need to consider the interactions between sensory modulation and attachment when addressing functional abilities with occupational therapy treatment.

Objective To report on intra- and perioperative complications associated with working channel endoscopic spine surgery. Methods This study is a retrospective chart review of a multi-institutional patient cohort operated on by surgeons within the Endoscopic Spine Study Group between May 2010 and June 2017. Results Our study cohort consists of a total of 553 consecutive cases with an average age of 57 years. The most common procedure was an endoscopic discectomy (n = 377, 68%) followed by foraminotomy (n = 156, 28.2%), unilateral laminotomy for bilateral decompression (n = 55, 9.9%), and lateral recess decompression (n = 29, 5.2%). Overall, the rate of intra- and perioperative complications was 2.7%. There were 3 durotomies (0.54%), 2 epidural hematomas (0.36%), 2 patients developed a complex pain disorder (0.36%), 4 recurrent disc herniations within 3 months (1.1%), 4 systemic complications (1.1%), and no wound infections. No risk factors were identified with regards to age, sex, approach, or number of segments. Conclusions Endoscopic spine surgery is associated with a favorable rate of intra- and perioperative complications compared with reported rates of minimally invasive ortraditional open spine surgeries. Our report proposes safe and effective strategies for management of these complications.

Postvasectomy pain syndrome (PVPS) can be debilitating and is notoriously difficult to treat, often requiring a multidisciplinary approach. In this case report, osteopathic manipulative treatment (OMT) was used to treat a patient with PVPS. After vasectomy, an otherwise-healthy man experienced chronic right testicular pain, aggravated by exercise, touch, and sexual intercourse, resulting in marital strain and an inability to perform routine fitness activities. Symptoms persisted for 8 years, despite lifestyle modifications, orally administered pain regimens, pelvic floor physical therapy, nerve blocks, steroid injections, epididymectomy, spermatic cord denervation, and counseling. After the patient's urologist suggested orchiectomy, his family medicine physician referred him for OMT. The OMT interventions, applied over a 4-month period, were directed at the lumbar spine, pelvis, pelvic floor, and lower abdomen. After treatment, the patient reported absence of testicular pain most of the time and described his quality of life as “10 times better.” Literature review revealed no reports of OMT used to manage PVPS.

Complex regional pain syndrome (CRPS) is a complex pain disorder that can emerge after limb trauma or a lesion in the peripheral nervous system. Typical features include continuing pain, sensory, vasomotor, sudomotor, motor, and trophic changes as well as edema. These signs provide the basis of CRPS diagnosis. A detailed description of the signs, symptoms, and medical history of CRPS could potentially facilitate an earlier and more accurate diagnosis. The aim of this study was to provide such a description, on the basis of epidemiological measures, clinical presentation, and a thorough description of pain sensations. Some signs (eg, differences of skin temperature >1°C), which have been thought to be crucial for diagnosis, were less common than assumed. We identified 11 distinct etiological triggers, which cover more than 99% of the study participants. We developed a weighted score on the basis of the most decisive data, which achieved a sensitivity of .869 and a specificity of .829, compared with .819 and .679 for the Budapest criteria. The weighted diagnostic criteria may help to better aid in distinguishing CRPS from other pain disorders. Perspective This article provides a retrospective epidemiological analysis of 1,043 CRPS patients compared with 421 patients with other pain disorders. The findings could potentially facilitate a more reliable and earlier diagnosis of CRPS, a better differentiation from other pain disorders, and ultimately in a more targeted and effective therapy.

Objective To evaluate the cost-effectiveness of the inclusion of trigger point-dry needling (TrP-DN) into an exercise program for the management of subacromial pain syndrome. Methods Fifty patients with unilateral subacromial pain syndrome were randomized with concealed allocation to exercise alone or exercise plus TrP-DN. Both groups were asked to perform an exercise program targeting the rotator cuff musculature twice daily for five weeks. Patients allocated to the exercise plus TrP-DN group also received dry needling during the second and fourth sessions. Societal costs and health-related quality of life (estimated by EuroQol-5D-5L) over a one-year follow-up were used to generate incremental cost per quality-adjusted life-year (QALY) ratios for each intervention. Results Intention-to-treat analysis was possible for 48 (96%) of the participants. Those in the exercise group made more visits to medical doctors and received a greater number of other treatments (P

The article of record as published may be found at http://dx.doi.org/10.1093/milmed/usx116 Sleep disorders are increasingly recognized in active duty service members (ADSM). While there are multiple studies in male ADSM, there are limited data regarding sleep disorders in women in the military. The purpose of this study was to characterize sleep disorders in female ADSM referred for clinical evaluation to provide a better understanding of this unique population. Materials and Methods: We conducted a retrospective review of female ADSM who underwent a sleep medicine evaluation and an attended polysomnogram (PSG). Demographic and polysomnogram variables, as well as medical records, were reviewed. Associated illnesses to include post-traumatic stress disorder, pain disorders, anxiety, and depression, were recorded. Results: The cohort consisted of 101 women. The average age was 33.9 ± 9.0 years and body mass index was 27.3 ± 4.5, with an average Epworth Sleepiness Scale score of 12.9 ± 5.2, and Insomnia Severity Index score of 17.6 ± 5.7. Overall, 36.6% were diagnosed with insomnia only, 14.9% with obstructive sleep apnea (OSA) only, and 34.7% met diagnostic criteria for both insomnia and OSA. The average apnea-hypopnea index for the entire cohort was 5.37 ± 7.04/h whereas it was 10.34 ± 3.14/h for those meeting diagnostic criteria for OSA. The women referred for sleep evaluations had the following rates of associated illnesses: pain disorders (59.4%), anxiety (48.5%), depression (46.5%), and post-traumatic stress disorder (21.8%). For patients with OSA, the relative risk of having post-traumatic stress disorder was 2.72 (95% confidence interval 1.16–6.39). Conclusions: Women in the U.S. military who have sleep disorders have a high rate of behavioral medicine and pain disorders. Interestingly, nearly 50% of active duty females referred for a sleep study have OSA while not necessarily manifesting the typical signs of obesity or increased age. The reasons for this finding are not completely understood, though factors related to military service may potentially contribute. The findings from our study indicate a need for increased awareness and evaluation of sleep disorders in women in the military, especially those with behavioral medicine disorders.

Post-treatment Lyme disease syndrome (PTLDS) is a pain disorder for which there remains no gold standard treatment option. Here, we report a case of PTLDS in a female patient whose pain was refractory to treatment options such as radiofrequency ablation, vitamin infusion therapy, opioid analgesics, and other pharmacotherapies. The patient commenced an experimental intravenous ketamine infusion therapy at the Florida Spine Institute (Clearwater, FL, USA) and achieved relief from her chronic pain, an improved quality of life, reduced depression and suicidal ideation, and reduced opioid consumption., Video abstract

Dominant mutations in voltage-gated sodium channel NaV1.7 cause inherited erythromelalgia, a debilitating pain disorder characterized by severe burning pain and redness of the distal extremities. NaV1.7 is preferentially expressed within peripheral sensory and sympathetic neurons. Here, we describe a novel NaV1.7 mutation in an 11-year-old male with underdevelopment of the limbs, recurrent attacks of burning pain with erythema, and swelling in his feet and hands. Frequency and duration of the episodes gradually increased with age, and relief by cooling became less effective. The patient's sister had short stature and reported similar complaints of erythema and burning pain, but with less intensity. Genetic analysis revealed a novel missense mutation in NaV1.7 (2567G>C; p.Gly856Arg) in both siblings. The G856R mutation, located within the DII/S4-S5 linker of the channel, substitutes a highly conserved non-polar glycine by a positively charged arginine. Voltage-clamp analysis of G856R currents revealed that the mutation hyperpolarized (-11.2 mV) voltage dependence of activation and slowed deactivation but did not affect fast inactivation, compared with wild-type channels. A mutation of Gly-856 to aspartic acid was previously found in a family with limb pain and limb underdevelopment, and its functional assessment showed hyperpolarized activation, depolarized fast inactivation, and increased ramp current. Structural modeling using the Rosetta computational modeling suite provided structural clues to the divergent effects of the substitution of Gly-856 by arginine and aspartic acid. Although the proexcitatory changes in gating properties of G856R contribute to the pathophysiology of inherited erythromelalgia, the link to limb underdevelopment is not well understood.

Objective Complex regional pain syndrome type 1 is a disabling pain disorder with unclear etiology. It is usually triggered by an injury to a limb with or without specific nerve injury. The objective of this study is to explore the risk factors and predictors for this disease utilizing a large national database. Design Retrospective analysis of the Nationwide Inpatient Sample database from 2007 to 2011 in the United States. Setting and patients Adult inpatients diagnosed with complex regional pain syndrome type 1. Statistical analysis Chi-square, simple and multivariate logistic regression analyses were conducted. The regression model was adjusted to the patient's demographics and comorbidities. Main results There were 22,533 patients with the discharge diagnosis of complex regional pain syndrome type 1 of an inpatient sample of 33,406,123. It peaks between age 45 and 55. Female gender, Caucasian race, higher median household income, headache, depression, drug abuse and private insurance patients (vs Medicaid patients) were associated with higher rate of complex regional pain syndrome type 1. On the other hand, diabetes, obesity, hypothyroidism, and anemia were associated with a lower rate. Conclusions Utilizing a large database, our study added more information to the risk profile of the complex regional pain syndrome type 1 in an inpatient population. Such information should be useful for physician for early recognition, diagnosis of patients at risk.

Voltage-gated sodium channel (NaV) mutations cause genetic pain disorders that range from severe paroxysmal pain to a congenital inability to sense pain. Previous studies on NaV1.7 and NaV1.8 established clear relationships between perturbations in channel function and divergent clinical phenotypes. By contrast, studies of NaV1.9 mutations have not revealed a clear relationship of channel dysfunction with the associated and contrasting clinical phenotypes. Here, we have elucidated the functional consequences of a NaV1.9 mutation (L1302F) that is associated with insensitivity to pain. We investigated the effects of L1302F and a previously reported mutation (L811P) on neuronal excitability. In transfected heterologous cells, the L1302F mutation caused a large hyperpolarizing shift in the voltage-dependence of activation, leading to substantially enhanced overlap between activation and steady-state inactivation relationships. In transfected small rat dorsal root ganglion neurons, expression of L1302F and L811P evoked large depolarizations of the resting membrane potential and impaired action potential generation. Therefore, our findings implicate a cellular loss of function as the basis for impaired pain sensation. We further demonstrated that a U-shaped relationship between the resting potential and the neuronal action potential threshold explains why NaV1.9 mutations that evoke small degrees of membrane depolarization cause hyperexcitability and familial episodic pain disorder or painful neuropathy, while mutations evoking larger membrane depolarizations cause hypoexcitability and insensitivity to pain.

Temporomandibular joint disorder (TMD) is a broad pain disorder that refers to several conditions affecting the temporomandibular joint of the jaw and the muscles of mastication. As with most pain disorders, a high prevalence of depression and anxiety is associated with TMD. Research has shown that selective serotonin reuptake inhibitors (SSRIs), the first-line drug therapy for major depressive disorder, may not be suitable for TMD patients because SSRIs can induce teeth-grinding, otherwise known as bruxism. This is problematic because bruxism is believed to further exacerbate TMD. Therefore, the purpose of this literature review is to better understand the mechanism of SSRI-induced bruxism, as well as discuss alternative antidepressant options for treating depression and anxiety in patients with bruxism and TMD. Alternative classes of antidepressants reviewed include serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, and monoamine oxidase inhibitors. Findings indicate that dopamine agonists and buspirone are currently the most effective medications to treat the side effects of SSRI-induced bruxism, but results regarding the effectiveness of specific antidepressants that avoid bruxism altogether remain inconclusive.

This paper presents a first study to apply a computational approach to Genito-Pelvic Pain/Penetration Disorder (GPPPD) using a Fear Avoidance Model. An adaptive temporal-causal network model for fear avoidance was designed and therapeutic interventions were incorporated targeting one or two emotional states. Validation with empirical data shows that for one type of individual therapeutic intervention targeting two states can reduce pain and other complaints. For three other types of individuals, targeting two emotional states was not sufficient to reduce pain and other complaints. The computational model can address large individual differences and supports the claim that interventions for GPPPD should be multidisciplinary.

Background Korea is one of the countries with the highest rate of suicide, while suicidality is known to be closely related to mental illnesses. The study aimed to evaluate the suicide rates in psychiatric patients, to compare it to that of the general population, and to investigate the differences among psychiatric diagnoses and comorbidities. Methods Medical records and mortality statistics of psychiatric patients at Seoul National University Hospital from 2003 to 2017 were reviewed. The standardized mortality ratio (SMR) for suicide was calculated to compare the psychiatric patients with the general population. The diagnosis-specific standardized mortality rate and hazard ratio (HR) were adjusted by age, sex, and psychiatric comorbidity (i.e., personality disorder and/or pain disorder). Results A total of 40,692 survivors or non-suicidal deaths and 597 suicidal death were included. The suicide rate among psychiatric patients was 5.13-fold higher than that of the general population. Psychotic disorder had the highest SMR (13.03; 95% confidence interval [CI], 11.23–15.03), followed by bipolar disorder (10.26; 95% CI, 7.97–13.00) and substance-related disorder (6.78; 95% CI, 4.14–10.47). In survival analysis, psychotic disorder had the highest HR (4.16; 95% CI, 2.86–6.05), which was further increased with younger age, male sex, and comorbidity of personality disorder. Conclusion All psychiatric patients are at a higher risk of suicide compared to the general population, and the risk is highest for those diagnosed with psychotic disorder., Graphical Abstract

Animal studies have shown that local injection of botulinum neurotoxins (BoNTs) reduces neuropathic pain. This effect is exerted via interfering with the function of pain transmitters and modulators at peripheral and central levels. Recent studies in humans have demonstrated an analgesic effect in several pain disorders. In this chapter, the effect of BoNT therapy in different medical, human pain syndromes is reviewed. The level of efficacy in each pain syndrome is determined according to the guidelines of the Assessment Subcommittee of the American Academy of Neurology.

There are a number of sleep changes that occur with age including increased sleep latency, an increasing frequency of nighttime arousals and awakenings, a decrease in the total time spent sleeping overnight, and a decrease in slow wave sleep. The prevalence of insomnia and other sleep disorders increases with age and can result in cognitive decline, increased risk of falls, worsening psychiatric and medical symptoms, and increased morbidity and mortality. In older adults, sleep pathology is often precipitated by or comorbid with medical (i.e., pain disorder) and psychiatric (i.e., depression and anxiety) disorders. Behavioral and environmental factors, medications, and medication side effects can also precipitate or exacerbate sleep disorders. In this chapter, we review age-related sleep changes, review the most common sleep disorders in the elderly, and discuss their diagnosis and management.

Fibromyalgia syndrome (FMS) is a complex pain disorder, characterized by diffuse pain and cognitive disturbances. Abnormal cortical oscillatory activity may be a promising biomarker, encouraging non-invasive neurostimulation techniques as a treatment. We aimed to modulate abnormal slow cortical oscillations by delivering transcranial alternating current stimulation (tACS) and physiotherapy to reduce pain and cognitive symptoms. This was a double-blinded, randomized, crossover trial conducted between February and September 2018 at the Rehabilitation Unit of a teaching Hospital (NCT03221413). Participants were randomly assigned to tACS or random noise stimulation (RNS), 5 days/week for 2 weeks followed by ad hoc physiotherapy. Clinical and cognitive assessments were performed at T0 (baseline), T1 (after stimulation), T2 (1 month after stimulation). Electroencephalogram (EEG) spectral topographies recorded from 15 participants confirmed slow-rhythm prevalence and provided tACS tailored stimulation parameters and electrode sites. Following tACS, EEG alpha1 ([8–10] Hz) activity increased at T1 (p = 0.024) compared to RNS, pain symptoms assessed by Visual Analog Scale decreased at T1 (T1 vs T0p = 0.010), self-reported cognitive skills and neuropsychological scores improved both at T1 and T2 (Patient-Reported Outcomes in Cognitive Impairment, T0–T2, p = 0.024; Everyday memory questionnaire, T1 compared to RNS, p = 0.012; Montréal Cognitive Assessment, T0 vs T1, p = 0.048 and T0 vs T2, p = 0.009; Trail Making Test B T0–T2, p = 0.034). Psychopathological scales and other neuropsychological scores (Trail Making Test-A; Total Phonemic Fluency; Hopkins Verbal Learning Test-Revised; Rey–Osterrieth Complex Figure) improved both after tACS and RNS but earlier improvements (T1) were registered only after tACS. These results support tACS coupled with physiotherapy in treating FMS cognitive symptoms, pain and subclinical psychopathology.