Pain Conditions Research Articles

Unani Regimenal Therapy for Knee Osteoarthritis (Waja ‘al Rukba): A Comprehensive Scientific Assessment

Pain in the joints has been a common and serious health issue for a long time. In Unani medicine, both inflammatory and non-inflammatory joint problems are grouped under the term "Waja‘al-Mafāṣil," which means joint pain. Osteoarthritis, based on its symptoms, is very similar to a condition in Unani medicine called Waja‘al-Mafāṣil Balghamī. One of the most common types of osteoarthritis is Knee Osteoarthritis (KOA), which is known in Unani medicine as Waja‘al Rukba. This chronic and painful condition is usually treated with non-steroidal anti-inflammatory drugs (NSAIDs), but these drugs can have many side effects. In contrast, the Unani system of medicine uses a more comprehensive approach to manage osteoarthritis. Waja‘al Rukba is managed with Istefragh (evacuation) followed by Tadeel Mizaj (rejuvenation), Taqwiyat (strengthened) and Taskeen (pain is relieved). Istefragh is achieved using specific Unani herbal treatments, like Munzij-Mushil Therapy followed by Tadeel Mizaj using various techniques, including Ḥijāma (cupping), Dalk (massage), Ta‘līq al-‘Alaq (leech therapy), Ḥammām (Turkish Bath), Takmeed (fomentation), Naṭūl (irrigation), Qay‘ (vomiting), and Ḥuqna (enema). Taskeen and Taqwiyat are achieved using either medications or these modalities. This overview focuses on Waja‘al Rukba and its Regimenal management. Keywords Ilājbi’lTadbīr, Osteoarthritis, Unani, Waja ‘al Rukba, Waja‘al Mafāṣil,

Glial-modulating agents for the treatment of pain: a systematic review.

Preclinical research supports a critical role for nervous system glia in pain pathophysiology. This systematic review of human trials of potential glia-modulating drugs for the prevention or treatment of pain followed a predefined search strategy and protocol registration. We searched for English language, randomized, double-blind trials comparing putative glia-modulating drugs to placebo or other comparators. The primary outcomes included validated participant-reported measures of pain intensity or relief and, in studies of opioid administration, measures of opioid consumption and/or opioid-related adverse effects. Twenty-six trials (2132 participants) of glial modulators (12 minocycline, 11 pentoxifylline, and 3 ibudilast) were included. Because of clinical heterogeneity related to study drug, participant population, outcome measures, and trial design, no meta-analysis was possible. Only 6 trials reported a positive effect of the treatment (pentoxifylline-4 trials; minocycline-2 trials), whereas 11 trials reported mixed results and 9 trials reported no effect. This review does not provide convincing evidence of efficacy of current pharmacological targets of nervous system glial function for pain treatment or prevention. However, in light of ample preclinical evidence of the importance of neuroimmune signalling and glial functions in pain pathophysiology, continued strategic human research is anticipated to identify (1) drugs with maximal activity as selectively targeted glial modulators, (2) the necessary timing and duration of pharmacological glial modulation needed for pain prevention or treatment for specific injuries or pain conditions, and (3) the best design of future clinical trials of glial-targeted drugs for pain treatment and/or prevention.

Investigation of the effect of catechol-o-methyltransferase gene rs4680 polymorphism on trigeminal neuralgia susceptibility

Research has been conducted to explore the genetic basis of trigeminal neuralgia, a persistent pain condition that impacts the trigeminal nerve. COMT is an enzyme responsible for inactivating substances and hormones containing catechol and catecholamines. Previous research has linked COMT gene polymorphism with various pain conditions, including migraine. Our research aimed to investigate the correlation between trigeminal neuralgia and the rs4680 polymorphism of the COMT gene. We conducted a research project which included 10 individuals diagnosed with trigeminal neuralgia and 30 healthy individuals as controls. Following collection of blood samples, we isolated DNA from the samples and then genotyping of COMT rs4680 polymorphism was performed with Real-Time PCR, using TaqMan SNP Genotyping Assay. Among the trigeminal neuralgia patients, 2 of them exhibited the AA genotype, 6 had the AG genotype, and 2 had the GG genotype for COMT rs4680. The AG genotype was notably prevalent. No statistically significant differences in the distributions of COMT genotypes and allele frequencies were found between the experimental (patients) and the control group. However, the AG genotype appeared to be more frequent in the patient group. Moving forward, we plan to expand our study by increasing the number of patients and control subjects. This will enable us to further elucidate the potential relationship between COMT gene polymorphism and trigeminal neuralgia.

Metabotropic Glutamate Receptor 5: A Potential Target for Neuropathic Pain Treatment.

Neuropathic pain, a multifaceted and incapacitating disorder, impacts a significant number of individuals globally. Despite thorough investigation, the development of efficacious remedies for neuropathic pain continues to be a formidable task. Recent research has revealed the potential of metabotropic glutamate receptor 5 (mGlu5) as a target for managing neuropathic pain. mGlu5 is a receptor present in the central nervous system that has a vital function in regulating synaptic transmission and the excitability of neurons. This article seeks to investigate the importance of mGlu5 in neuropathic pain pathways, analyze the pharmacological approach of targeting mGlu5 for neuropathic pain treatment, and review the negative allosteric mGlu5 modulators used to target mGlu5. By comprehending the role of mGlu5 in neuropathic pain, we can discover innovative treatment approaches to ease the distress endured by persons afflicted with this incapacitating ailment.

Characteristics of men and women with medically diagnosed cluster headache in a national integrated healthcare system: A Veterans Health Administration cohort study.

Describe the epidemiology of cluster headache (CH) using Veterans Health Administration (VHA) Electronic Health Record (EHR) data. Epidemiologic studies of CH at the population level are difficult because it has a prevalence of ~0.1%. Hospital system-wide studies are an attractive alternative as they have large numbers of patients and broader populations than headache or neurology clinic-based studies. The VHA is an ideal hospital-based system in which to study CH because it is nationwide, predominantly male, has a strong focus on mood disorders and suicidality, and has accessible individual medical records. Here, we report the first headache study based on an ongoing longitudinal cohort of patients with CH using VHA EHR data. The VHA EHR data were accessed from Fiscal Year 2008 to 2019. Patients with CH consisted of all patients with at least one outpatient visit containing a CH diagnosis code from the International Classification of Diseases (ICD)-9 or -10. We extracted data on demographic features, incidence, and prevalence, as well as pain and psychiatric comorbidities. Of the 1,524,960 distinct patients who presented for headache treatment in the VHA between Fiscal Year 2008-2019, 24,131 had at least one visit with a CH diagnosis. The 1-year period prevalence of a CH diagnosis in the VHA ranges from 0.08% to 0.10% for women and 0.10% to 0.18% for men. A larger proportion of women versus men received a diagnosis of unspecified CH (59.6% [1412/2368] vs. 53.6% [11,663/21,763], p < 0.001). Most patients with CH had both comorbid headache and non-headache pain diagnoses. Headache not-otherwise-specified was the most common comorbid headache disorder at 70.0% (16,885/24,131) and was more common in women (76.1%, 1801/2368) compared to men (69.3%, 15,084/21,763). Other common comorbidities included migraine, depression, tobacco use, and obstructive sleep apnea. Rates of suicidal ideation or attempt were almost 50% higher in women (5-year proportion 9.4%, 222/2368) with CH compared to men (6.6%, 1433/21,763). To our knowledge this is the largest hospital system study of CH to date and reinforces several previous studies. Pain, mental health, and sleep disorders comorbidities are particularly prevalent in this group and were often more common in women compared to men with CH. Future work should examine gender and race stratified prevalence estimates within the VHA and other healthcare systems.

Predictors of Persistent Pain after Total Knee Arthroplasty

Background: Total knee arthroplasty (TKA) is an orthopedic procedure performed on patients with severe knee pain and advanced knee conditions, such as osteoarthritis and rheumatoid arthritis, in order to restore joint function. Despite the procedure’s high success rates, persistent postoperative pain (PPP) remains a significant complication, affecting a substantial proportion of patients. Identifying predictors of PPP is crucial for improving patient outcomes and satisfaction. Methods: A retrospective analytic study was conducted, reviewing the medical records of patients who underwent unilateral or bilateral TKA at King Abdulaziz Medical City. The data collection focused on demographics, comorbidities, clinical presentations, surgical details, and postoperative outcomes. Data were analyzed using JMP software. A p-value of less than 0.05 was considered statistically significant. Results: This study included 838 patients, predominantly female (71.5%), with an average age of 65.4 years. Osteoarthritis was the primary reason for surgery (98.3%). The mean preoperative pain score was 3.4, and the average pain duration prior to surgery was 6.2 years. We identified dyslipidemia as a significant predictor of PPP (OR 1.40, p = 0.042), while we found younger age to be a significant predictor (OR 0.979, 95% CI 0.967–0.991, p = 0.001). Other factors such as gender, diabetes, hypertension, cardiovascular disease, anxiety disorder, mood disorder, tobacco use, chronic kidney disease, chronic lung disease, and BMI were not significant predictors of PPP. Conclusion: This study identifies younger age and dyslipidemia as significant predictors of persistent postoperative pain and improved outcomes following total knee arthroplasty Further research is needed to validate these results in diverse populations and settings, with the objective should be to refine preoperative counseling and postoperative pain management protocols.

Characteristics of patients with somatoform pain disorder

AbstractBackgroundPatients with somatoform pain experience physical pain that cannot be attributed to any underlying medical or physiological cause, and it is often thought to be related to psychological factors. Health professionals encounter difficulties identifying this specific type of chronic pain, leading to suboptimal treatment strategies. Therefore, we aimed to describe the characteristics of patients with somatoform pain, to support the identification of affected patients.MethodsWe collected and analyzed a cross‐sectional survey data from 200 patients with somatoform pain admitted to one of three psychosomatic centers in Germany between August 2013 and July 2014. The survey contains 10 different categories, all of them referring to pain‐related topics. Within the survey, we analyzed validated as well as non‐validated questionnaires. Here, we present the following five: Personal data, Body: Pain perception, Cognition: Pain processing, Pain behavior, and Physical complaints.ResultsOur results highlight that most patients with somatoform pain experience it in several body parts and as persisting, lasting &gt;12 h/day (50%), and constantly changing (71%). Furthermore, patients indicate feelings of helplessness, by agreeing to the expressions the pain controls me (70%). Finally, we found that pain is predominantly seen as suffering, failing to convey emotional pain, despite cognitively acknowledging the dependency of emotional and physical pain.ConclusionThe study identified specific and distinctive characteristics in the emotional and behavioral responses of patients with somatoform pain, potentially distinguishing them from other patients with chronic pain.

Suppression of Visceral Nociception by Selective C-Fiber Transmission Block Using Temporal Interference Sinusoidal Stimulation.

Chronic visceral pain management remains challenging due to limitations in selective targeting of C-fiber nociceptors. This study investigates temporal interference stimulation (TIS) on dorsal root ganglia (DRG) as a novel approach for selective C-fiber transmission block. We employed (1) GCaMP6 recordings in mouse whole DRG using a flexible, transparent microelectrode array for visualizing L6 DRG neuron activation, (2) ex vivo single-fiber recordings to assess sinusoidal stimulation effects on peripheral nerve axons, (3) in vivo behavioral assessment measuring visceromotor responses (VMR) to colorectal distension in mice, including a TNBS-induced visceral hypersensitivity model, and (4) immunohistological analysis to evaluate immediate immune responses in DRG following TIS. We demonstrated that TIS (2000 Hz and 2020 Hz carrier frequencies) enabled tunable activation of L6 DRG neurons, with the focal region adjustable by altering stimulation amplitude ratios. Low-frequency (20-50 Hz) sinusoidal stimulation effectively blocked C-fiber and Aδ-fiber transmission while sparing fast-conducting A-fibers, with 20 Hz showing highest efficacy. TIS of L6 DRG reversibly suppressed VMR to colorectal distension in both control and TNBS-induced visceral hypersensitive mice. The blocking effect was fine-tunable by adjusting interfering stimulus signal amplitude ratios. No apparent immediate immune responses were observed in DRG following hours-long TIS. In conclusion, TIS on lumbosacral DRG demonstrates promise as a selective, tunable approach for managing chronic visceral pain by effectively blocking C-fiber transmission. This technique addresses limitations of current neuromodulation methods and offers potential for more targeted relief in chronic visceral pain conditions.

Phase I clinical trial evaluating the safety, tolerance, pharmacokinetics and pharmacodynamics of HSK21542 injection in healthy volunteers.

HSK21542 injection is a new peripheral kappa opioid receptor (KOR) agonist. To evaluate its safety, tolerability, pharmacokinetics and pharmacodynamics, this study was conducted in healthy volunteers, consisting of two parts: a single ascending dose (0.2-3.375 μg/kg, 15-min infusion) and different infusion durations (0.2 and 1μg/kg, 2- or 15-min infusion). The area under the plasma concentration-time curve (AUC) and peak concentration (Cmax) of HSK21542 were dose-linear among 0.2-3.375 μg/kg. After intravenous injection, HSK21542 was rapidly eliminated with a half-life (t1/2) of 1.5h, and the majority (48.02%) of the dose was excreted unchanged in urine. Pharmacodynamic results showed that HSK21542 increased prolactin release and reached a peak at 1-2h after administration but had no significant effect on vasopressin levels. There was a brief increase in urine volume within the initial 2h after administration. HSK21542 was well tolerated; most of the adverse effects (AEs) in the trial group were grade 1, and only 2 cases (4.0%) were grade 2. The main AE was paresthesia, which appeared in 42% (21/50) in the trial group. No serious adverse event (SAE) was observed. No subject withdrew early due to AEs. These results suggest that HSK21542 may be a potential treatment for pain and pruritic conditions.

Rehabilitation Interventions for Adults With Complex Regional Pain Syndrome: A Scoping Review Protocol.

This scoping review will explore the literature related to rehabilitation interventions for the treatment of adults living with complex regional pain syndrome (CRPS), describe the domains and outcome measures used to assess their effectiveness, and examine the neurophysiological bases of these interventions. The unremitting symptoms of CRPS, a chronic pain condition, are associated with long-term disability, poor psychological health, decreased emotional and social well-being, and reduced quality of life. Effective treatment for persistent symptoms is notoriously difficult. Therapeutic approaches such as graded motor imagery or pain exposure therapy are recommended for CRPS but show mixed results, insufficient effectiveness, variability in outcome measures, and unclear neurophysiological bases. This review will consider studies that include any form of non-invasive rehabilitation intervention delivered by a healthcare professional in any setting for adults with a CRPSdiagnosis. Quantitative, qualitative and observational studies, text and opinion papers will be considered. The Joanna Briggs Institute (JBI)methodology will be used to conduct this scoping review. MEDLINE, Embase, Scopus, APA PsycINFO, CINAHL, Cochrane, OpenGrey Google and ProQuest Dissertations and Theses Global (ProQuest) will be searched for studies in English published between 2007 and 2024. Two independent reviewers will screen the titles, abstracts, and full texts of the selected studies. Data collection will be performed using a tool developed by the researchers based on the standardised JBI tool. Data will be presented in a comprehensive narrative summary. https://doi.org/10.17605/OSF.IO/P967T.

The effectiveness of massage gun treatment combined with passive stretching in reducing non-specific lower back pain

Non-specific lower back pain is a common condition characterized by strain, muscle spasms, or weakness of the paraspinal muscles, particularly the multifidus muscle, which affects adjacent musculature such as the gluteus, hamstrings, and quadriceps. This study aimed to investigate whether massage gun treatment combined with passive stretching could reduce non-specific low back pain in patients experiencing subacute and chronic phases of this condition. This pseudo-experimental research employed a one-group pretest-posttest design with three treatments. Participants were selected using purposive sampling based on inclusion criteria: suffering from non-specific low back pain, willingness to participate, and age between 20 and 65 years. Exclusion criteria included anatomical abnormalities of the spine, fractures, open wounds, and specific spinal disorders. The visual analog scale (VAS) was used to measure pain intensity before and after each treatment session. Initial VAS scores averaged 65.6 units. Following the first treatment, scores decreased significantly to 52.1 units; subsequent reductions occurred at 42.1 units post-second treatment and 33.5 units post-third treatment. Statistical analysis revealed a significant difference across all three treatment sessions (p = 0.000 0.05), indicating a progressive improvement in pain control over time. Massage gun therapy coupled with passive stretching demonstrated efficacy in reducing non-specific lower back pain among participants. These findings suggest that repeated application of these interventions can lead to sustained improvements in pain management for individuals suffering from subacute and chronic non-specific low back pain conditions

Is sexual function impaired in patients with primary headaches? A systematic review of observational studies.

Primary headaches, particularly migraine and tension-type headaches, as chronic and painful conditions, have a significant impact on individuals' health and overall quality of life, including aspects such as sexual health parameters. The aim of this study was to review observational studies and to summarize the presence of sexual dysfunction in patients with primary headache and to discern whether it is more common in patients with primary headache than in healthy control subjects. Observational studies published between January 1, 2000, and May 21, 2023 were searched in Medline (PubMed), Web of Science, Scopus, and EBSCO. This review included 23 observational studies that evaluated sexual dysfunction with or without comparison with healthy control subjects. As a result, the mean Female Sexual Function Index score, a score of <26.55 indicating sexual dysfunction, ranged from 19.25 ± 8.18 to 27.5 ± 7.5 in patients with primary headache. The prevalence of sexual dysfunction and erectile dysfunction was found to be between 10.7% and 93.75% in female patients and between 54.83% and 80% in male patients. Both migraineurs and tension-type headache sufferers had statistically significantly lower sexual function scores in females and lower erectile function scores in males compared with healthy control subjects. Sexual function is significantly affected in patients with primary headache, which is a chronic painful disorder. Therefore, it is very important to ask these patients about their sexual health and, if necessary, to seek support from a sexual health professional. Additionally, future studies may prioritize tension-type headaches and male patients due to the limited amount of research available on these subjects.

A Pilot Study Examining The Efficacy Of Occupational Therapy Rehabilitation Programmes For Students With Work-Related Muscular-Skeletal Disorders

Background: Musculoskeletal issues at work have an influence on daily life, productivity, and quality of life. Musculoskeletal issues that go untreated can result in severe damage and function loss, which can limit participation, cause financial loss, and add to the rising burden of illness in the world. Objective: The purpose of this study was to find the effect of occupational therapy rehabilitation program in occupational therapy students with work related musculoskeletal disorder. Study Design:Quasi-experimental, pilot study design was chosen for the research Methods: The study employed a quasi-experimental study design. Thirty occupational therapy students aged 20-25 years were recruited through convenience sampling after a prevalence check where 30 students reported 54 musculoskeletal problems. A total number of participants (n= 30) received occupational therapy rehabilitation program. Standardised Nordic musculoskeletal questionnaire (SNMQ) and Numeric pain rating scale (NPRS) were administered to Pain and work related musculoskeletal disorder for all the participants. Result: It revealed that there was a statistically significant difference in pre-test and post-test with numeric pain rating scale (t=10.625, p=0.000). There was a significant difference in percentage in 7 days component of SNMQ. There was no statistical difference with post-test of score of 12 months component of SNMQ. Conclusion: Occupational therapy rehabilitation program is effective for reducing Musculoskeletal disorder or discomfort in occupational therapy students.

Pain profiles and variability in temporal summation of pain and conditioned pain modulation in pain-free individuals and patients with low back pain, osteoarthritis, and fibromyalgia.

Pain profiles (e.g. pro- and anti-nociceptive) can be developed using quantitative sensory testing (QST) but substantial variability exists. This study describes the variability in temporal summation of pain (TSP) and conditioned pain modulation (CPM) in chronic musculoskeletal pain patients, proposes cut-off values, and explores the association with clinical pain intensity. This is a secondary analysis in which TSP and CPM were assessed using cuff algometry in pain-free subjects (n = 69), and patients with chronic low back pain (cLBP, n = 267), osteoarthritis (n = 134), and fibromyalgia (n = 101). Using TSP and CPM from the pain-free subjects as a reference, four distinct pain profiles TSP (low/high) and CPM (low/high) were created, and differences in clinical pain between pain profiles were explored. Individual data revealed large inter-person variability. High TSP and low CPM were found in fibromyalgia (p < 0.01) and osteoarthritis (p < 0.01) but not cLBP when compared to pain-free subjects. The proportion of patients classified into the distinct pain profiles was significantly different (p < 0.001) with the largest proportion in the high TSP and low CPM group in fibromyalgia (52.5%) and osteoarthritis (41.4%). Clinical pain was not significantly different comparing the pain profiles, and no significant correlations were observed between clinical pain and TSP or CPM. These results demonstrated substantial inter-person variability in TSP and CPM in patients with different chronic pain conditions and pain-free subjects. The proportion of patients with a pro-nociceptive profile appears larger in fibromyalgia and osteoarthritis, but we found no association to clinical pain. This analysis shows that there is variability when assessing TSP and CPM in both pain-free subjects and patients with chronic pain. A cut-off for determining when a person is pain-sensitive is proposed, and data based on this cut-off approach suggest that significantly more patients with osteoarthritis and fibromyalgia are pain-sensitive (i.e. higher TSP and lower CPM) compared to pain-free subjects. This analysis does not find an association between pain sensitivity and clinical pain.

Clinical Efficacy of Auricular Vagus Nerve Stimulation in the Treatment of Chronic and Acute Pain: A Systematic Review and Meta-analysis.

Current guidelines for pain treatment recommend a personalized, multimodal and interdisciplinary approach as well as the use of a combination of drug and non-drug therapies. Risk factors for chronification should already be reduced in patients with acute pain, e.g., after surgery or trauma. Auricular vagus nerve stimulation (aVNS) could be an effective non-drug therapy in the multimodal treatment of chronic and acute pain. The aim of this systematic review and meta-analysis is to evaluate the clinical efficacy and safety of aVNS in treating chronic and acute pain conditions. A systematic literature search was performed regarding the application of auricular electrical stimulation in chronic and acute pain. Studies were classified according to their level of evidence (Jadad scale), scientific validity and risk of bias (RoB 2 tool) and analyzed regarding indication, method, stimulation parameters, duration of treatment and efficacy and safety. A meta-analysis on (randomized) controlled trials (using different comparators) was performed for chronic and acute pain conditions, respectively, including subgroup analysis for percutaneous (pVNS-needle electrodes) and transcutaneous (tVNS-surface electrodes) aVNS. The visual analog pain scale (VAS) was defined as primary efficacy endpoint. A total of n = 1496 patients were treated with aVNS in 23 identified and analyzed studies in chronic pain, 12 studies in acute postoperative pain and 7 studies in experimental acute pain. Of these, seven studies for chronic pain and six studies for acute postoperative pain were included in the meta-analysis. In chronic pain conditions, including back pain, migraine and abdominal pain, a statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control treatment with an effect size Hedges' g/mean difference of - 1.95 (95% confidence interval [CI]: - 3.94 to 0.04, p = 0.008) could be shown and a more favorable effect in pVNS compared to tVNS (- 5.40 [- 8.94; - 1.85] vs. - 1.00 [- 1.55; - 0.44]; p = 0.015). In acute pain conditions, single studies showed significant improvements with aVNS, e.g., in kidney donor surgery or tonsillectomy but, overall, a non-statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control with - 0.70 [- 2.34; 0.93] (p = 0.15) could be observed in the meta-analysis. In acute pain results vary greatly between studies depending especially on co-medication and timepoints of assessment after surgery. A significant reduction in analgesics or opiate intake was documented in most studies evaluating this effect in chronic and acute pain. In 3 of the 12 randomized controlled trials in patients with chronic pain, a sustainable pain reduction over a period of up to 12months was shown. Overall, aVNS was very well tolerated. This systematic review and meta-analysis indicate that aVNS can be an effective and safe non-drug treatment in patients with specific chronic and acute postoperative pain conditions. Further research is needed to identify the influence of simulation parameters and find optimal and standardized treatment protocols while considering quality-of-life outcome parameters and prolonged follow-up periods. A more standardized approach and harmonization in study designs would improve comparability and robustness of outcomes.

The association of pain screening and pain level with suicide among US veterans with comorbid musculoskeletal and bipolar disorder diagnoses

BackgroundHigh suicide rates are documented among persons with bipolar disorder diagnoses and pain diagnoses, but few studies have examined the association of pain with suicide mortality in individuals with comorbid pain and bipolar disorders. This study assessed the association of pain screening and pain severity with suicide mortality among veterans with comorbid bipolar and musculoskeletal disorder (MSD) diagnoses. MethodsA retrospective cohort study was conducted on 168,021 patients within the Veterans Health Administration (VHA) who received an MSD diagnosis from 2000 to 2015 and had a bipolar disorder diagnosis. Pain severity, comorbidities, demographics, and suicide mortality were extracted from VHA databases. Poisson regression examined relative risk of suicide by the presence pain screening and pain severity ratings. ResultsPain was assessed in 72.73 % of veterans. Suicide risk was greater in those not assessed (0.98 % versus 0.77 % in assessed group). However, this result did not persist after adjusting for covariates (RR = 1.06). Among those assessed, higher suicide risk was associated with moderate (RR = 1.10), severe pain (RR = 1.06), and no pain (reference) relative to mild pain (RR = 0.99). Major depression, substance use disorders, and prescribed opioids and benzodiazepines increased risk. LimitationsData were obtained from medical records; diagnoses were not confirmed via formal assessment, and no information was available on actual medication use or purpose. Over 25 % of the sample were missing pain severity ratings, which could have affected results. ConclusionsSuicide risk factors among persons with bipolar disorder are complex and multifactorial. Providers should prioritize suicide prevention efforts following new onset or worsening pain.

Non-Migraine Head Pain and Botulinum Toxin.

Botulinum toxin A (BT-A), a potential neurotoxin produced by the bacterium Clostridium botulinum, is known for its ability to prevent the release of acetylcholine at the neuromuscular synapse, leading to temporary muscle paralysis. BT-A is used for a wide range of therapeutic applications. Several studies have shown mechanisms beyond the inhibition of acetylcholine release for pain control. BT-A inhibits the release of neurotransmitters associated with pain and inflammation, such as glutamate, CGRP, and substance P. Additionally, it would be effective in nerve entrapment leading to neuronal hypersensitivity, which is known as a new pathogenesis of painful conditions. BT-A has been applied to the treatment of a wide variety of neurological disorders. Since 2010, BT-A application has been approved and widely used as a chronic migraine prophylaxis. Moreover, due to its effects on pain through sensory modulation, it may also be effective for other headaches. Several studies using BT-A, at different doses and administration sites for headaches, have shown beneficial effects on frequency and severity. In this review, we provide an overview of using BT-A to treat primary and secondary headache disorders.

Causal impacts of smoking on pain conditions and the mediating pathways: a mendelian randomization study.

Smoking is a risk factor for multiple diseases. We performed mendelian randomization (MR) analyses to investigate the causal association of smoking initiation on pain conditions and the potential mediating pathways. Genetic associated with smoking initiation at the genome-wide significance level were selected as instrumental variables. Genetic associations with 10 pain conditions were derived from the FinnGen and UK Biobank study. Multivariable MR analysis was conducted to explore the mediation effects of depression, insomnia and sedentary behavior. A series of sensitivity analyses were conducted to assess the stability of our research findings. Genetic liability to smoking initiation was associated with an increased risk of angina pectoris, dorsalgia, low back pain, pain in limb, pain in joint, pain in thoracic spine and sciatica in both FinnGen and UK Biobank study. These causal associations were largely mediated by major depression (2.9- 39.5%), sedentary behavior (13.0- 31.2%), insomnia (10.3- 33.1%) and combination of all three mediators (30.2- 65.3%). The effects of smoking on outcomes were partly attenuated after adjusting for depression, sedentary behavior and insomnia respectively, and the direct effect of smoking initiation on pain was diminished toward null after adjusting for combined three mediators. These results were robust to sensitivity analyses. Our findings illustrated the causal effect of smoking and a broad range of pain conditions, and major depression, sedentary behavior and insomnia mediate many of these associations.

Exploring vagal neuromodulation: a novel approach to managing pain sensitivity in irritable bowel syndrome

Exploring vagal neuromodulation: a novel approach to managing pain sensitivity in irritable bowel syndrome Irritable bowel syndrome (IBS) is a common, chronic gastrointestinal disorder characterised by recurring abdominal pain and discomfort. This project will work under the hypothesis that IBS is linked to a malfunctioning of the brain-gut communication axis and proposes to address this dysfunction through transcutaneous electrical vagus nerve stimulation. To assist in identifying IBS patients suitable for this treatment, the study team aims to develop a neural signature using biometrics and neuroimaging. The study has the potential to revolutionise the treatment of IBS and other pain disorders, providing personalised and effective therapies.

The role of environmental sensitivity, traumatic experiences, defense mechanisms and mental pain on central sensitivity: testing a path analysis model in chronic headache on quality of life.

Central pain sensitivity (CS) is defined as an increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold inputs. The main aim of this paper is to investigate if and how specific psychological constructs are related with CS burden in patients with chronic headache (CH). Specifically, research question 1 explores the association of temperament, personality, childhood adversities, defense mechanisms and mental pain with CS burden. Research question 2 aims to test the role of the best predictors of CS burden in affecting the quality of life (QoL) using path analysis. A total of 508 women with CH completed a psycho-diagnostic survey. Results showed that higher levels of low sensory threshold (β = 0.200), bodily threat traumatic experiences (β = 0.156), neurotic defenses (β = 0.109) and mental pain (β = 0.343) emerged as the best predictors of higher CS burden. The model presented demonstrated a satisfactory fit (GFI = 0.984; NFI = 0.966; CFI = 0.979; RMSEA = 0.056 [95% CI 0.028-0.085]) with large and medium effect sizes on physical (-0.654) and psychological QoL (-0.246). The study showed a key role of psychological dimensions in CS burden levels and their relationships with QoL in CH patients. From a clinical perspective, these results suggest the importance of evaluating the level of CS burden during the clinical assessment for chronic pain conditions such as CH, since it may contribute to guide patients to tailored psychological and medical treatments, thereby saving time and costs on diagnostic procedures for chronic pain.