Chronic Pain Conditions Research Articles

Unveiling the Role of Human PER3 Gene Polymorphism (rs57875989) as a Potential Risk Factor in Fibromyalgia Syndrome Patients.

Purpose Fibromyalgia syndrome (FMS) presents a chronic pain condition affecting muscles and joints. Investigating circadian rhythms' disruption, integral to physiological responses, this study delves into the potential impact ofPER3CLOCK gene polymorphism (rs57875989) on FMS pathogenesis. Methods In this study, we investigated PER3 gene polymorphism in 100 FMS patients and an equal number of control individuals. The genotyping of the PER3 gene polymorphism was conducted using polymerase chain reaction (PCR) methodology. Subsequently, we evaluated the association betweenPER3gene polymorphism and FMS susceptibility using odds ratios (ORs) and 95% confidence intervals (CIs) by comparing the genotype and allele frequencies ofthe PER3gene polymorphism between FMS patients and controls. Results The PER3gene revealed three genotypes: 4/4, 4/5, and 5/5, with allele frequencies showing significant associations between FMS patients and controls (p<0.05). Notably,PER3gene polymorphism was linked to FMS development, particularly the 4/4 genotype versus the combined 4/5 and 5/5 genotypes (OR=2.85; 95% CI, 1.35-6.0; p=0.008). These findings suggest a potential role ofPER3gene variation as a genetic risk factor for FMS. Conclusion These findings reported a potential association betweenPER3gene polymorphism and FMS, illuminating novel pathways for comprehending and addressing this complex condition. This study holds promise for advancing our understanding of FMS etiology and may inform the development of innovative management strategies tailored to individual genetic profiles, potentially leading to more effective treatments and improved outcomes for patients grappling with FMS.

Esketamine infusion as treatment for chronic endometriosis-associated pain? Study protocol for a randomized controlled trial (EASYlight-study)

Current treatment options for chronic endometriosis-associated pain are often inadequate, resulting in a rise in opioid consumption in this population. Given its analgesic, anti-inflammatory, and anti-depressive properties, esketamine may be a promising alternative treatment option. While esketamine is globally used in the treatment of chronic pain conditions, no clinical trials have been conducted to investigate the efficacy of esketamine infusion to alleviate chronic endometriosis-associated (pelvic) pain. Therefore, the objective of this double-blinded randomized controlled trial (RCT) is to assess the efficacy of 8-h infusion with esketamine versus placebo (saline) to reduce chronic endometriosis-associated pain symptoms. Secondary study objectives include pain scores, quality of life, depressive symptoms, health care utilization, productivity loss, cost-effectiveness, side effects, treatment experience, and pain coping and cognition. Premenopausal women (aged ⩾18 years) diagnosed with endometriosis (peritoneal, ovarian, deep, or adenomyosis), with an indication for laparoscopic endometriosis resection surgery and who suffer from chronic pelvic pain (NRS score ⩾6) will be eligible for inclusion. In total, we aim to include 56 participants, with a follow-up of 12 weeks. Digital questionnaires will be sent at baseline and 4, 8, and 12 weeks after the day of infusion. Trial registration number The EASYlight study is registered as “EASYlight-NEK” in the Clinical Trials Register (NCT06161805)

Altered blood and keratinocyte microRNA/transfer RNA fragment profiles related to fibromyalgia syndrome and its severity.

Fibromyalgia syndrome (FMS) is a debilitating widespread chronic pain condition of unclear pathophysiology. We studied small noncoding RNAs as potential classifiers and mediators of FMS. Blood and keratinocyte microRNAs (miRs) and transfer RNA fragments (tRFs) were profiled by small RNA-sequencing within a comprehensively phenotyped female cohort of 53 patients with FMS vs 34 healthy controls (hCOs) and 15 patients with major depression and chronic physical pain (disease controls). Small RNAs were quantified via RNA-sequencing and candidates validated via qRT-PCR. MicroRNAs and tRFs were tested for association with FMS symptoms and their potential regulatory roles. miR and tRF profiles were altered in FMS compared to hCO in whole blood (n = 69; n = 22) and keratinocytes (n = 41; n = 55). Receiver operating characteristic analysis of blood miR candidates hsa-miR-148a-3p and hsa-miR-182-5p, and tRF candidate tRF-21-WB8647O5D levels separated FMS from hCO. In blood, hsa-miR-182-5p and hsa-miR-576-5p upregulation was validated via qRT-PCR, showing even higher expression in disease control, while TRF-20-40KK5Y93 was selectively increased in FMS. MicroRNAs in blood and keratinocytes were associated with how widespread pain manifested in patients. Keratinocyte tRFs correlated with loss of skin innervation. In blood, altered small RNAs were linked to immune and RNA processes, whereas in keratinocytes, adhesion and epithelial functions were targeted. Modulated tRFs shared sequence motifs in patients with FMS, which may promote concerted pathway regulation. Our findings show miRs/tRFs as key small RNAs dysregulation in FMS pathophysiology and open new perspectives for FMS diagnostics, symptom monitoring, and clinical management.

A genome-wide association study of European advanced cancer patients treated with opioids identifies regulatory variants on chromosome 20 associated with pain intensity.

Opioids in step III of the WHO analgesic ladder are the standard of care for treating cancer pain. However, a significant minority of patients do not benefit from therapy. Genetics might play a role in predisposing patients to a good or poor response to opioids. Here, we investigated this issue by conducting a genome-wide association study (GWAS). We genotyped 2057 European advanced cancer patients treated with morphine, buprenorphine, fentanyl and oxycodone. We carried out a whole-genome regression model (using REGENIE software) between genotypes and the opioid response phenotype, defined as a numerical score measuring patient pain intensity. The GWAS identified five non-coding variants on chromosome 20 with a p-value <5.0 × 10-8. For all of them, the minor allele was associated with lower pain intensity. These variants were intronic to the PCMTD2 gene and were 200 kbp downstream of OPRL1, the opioid related nociceptin receptor 1. Notably according to the eQTLGen database, these variants act as expression quantitative trait loci, modulating the expression mainly of PCMTD2 but also of OPRL1. Variants in the same chromosomal region were recently reported to be significantly associated with pain intensity in a GWAS conducted in subjects with different chronic pain conditions. Our results support the role of genetics in the opioid response in advanced cancer patients. Further functional analyses are needed to understand the biological mechanism underlying the observed association and lead to the development of individualized pain treatment plans, ultimately improving the quality of life for cancer patients. This genome-wide association study on European advanced cancer patients treated with opioids identifies novel regulatory variants on chromosome 20 (near PCMTD2 and OPRL1 genes) associated with pain intensity. These findings enhance our understanding of the genetic basis of opioid response, suggesting new potential markers for opioid efficacy. The study is a significant advancement in pharmacogenomics, providing a robust dataset and new insights into the genetic factors influencing pain intensity, which could lead to personalized cancer pain management.

Headaches and adolescents: why so many failures in their management

The management of headaches in children and adolescents is still a challenge, with patients experiencing pain for years and polypharmacy. We reviewed the medical history of 31 patients referred to our pain clinic for chronic headaches between April 2023 and April 2024. There were more female than male patients (73%). Patients have been reporting headaches for 52 ± 44 months on average. Twenty-nine patients (94%) were experiencing different types of pain besides headaches. The most common medication prescribed in this group of patients was topiramate (70%), followed by tricyclic antidepressants (35%) and triptans (21%). Patients had been prescribed and tried, on average, 4.5 ± 2 (range 1–10) different medications to manage headaches and concomitant psychiatric disorders. Twenty-two patients (71%) had been diagnosed with a psychiatric disorder, including depression, anxiety, and PTSD, and 16% had a history of attempted suicide/self-harm. Fourteen of them (45%) had been prescribed antidepressants or benzodiazepines. They had been prescribed, on average, 2 ± 1 (range 1–4) psychiatric stabilizer medications. We agreed with the referral diagnosis in 39% of the patients. We attributed the headaches to more complex chronic pain conditions, including fibromyalgia (15%) and AMPS (15%), autism with sensory integration problems (9%), and major depression (9%). Patients had seen an average of 3 ± 1 (range 1–5) different specialists; none consulted a pain specialist. Patients underwent between 0 (12%) and four tests (6%), including MRI (52%) and CT of the brain (8%). These neuroimaging studies did not demonstrate any brain pathology. We prescribed new medications and treatments, including nerve blocks, in 19 (61%) patients. In 47% of the cases, patients reported improved headaches, while 22% did not feel our recommendations were effective. Twenty-one percent of patients never came back to the clinic for a follow-up. Significant catastrophizing was present in 57% of the patients; 52% of patients had mild to severe anxiety, and 57% had symptoms of depressive disorder. Conclusions: Headaches are often the manifestation of more complex pain syndromes that require a more holistic approach, different from conventional pharmacological management.What is Known:• Headache is one of the most disabling diseases.• Prevalence of headaches in hildrens and adolescents can be as high as 58%.What is New:• Conventional pharmacological management often fails to help young patients.• A relationship between chronic headaches and psychopathology should be investigated in these young patients.

Combining Acmella oleracea and Boswellia serrata extracts: a novel pharmacological approach in inflammatory vestibulodynia.

Vulvodynia is a chronic pain condition that affects the vulvar area, often resulting in significant discomfort and a reduced quality of life. Current treatments for vulvodynia are limited, and there is a need for more effective therapeutic options. Acmella oleracea, known for its spilanthol content, and Boswellia serrata, rich in boswellic acids, have been explored for their potential analgesic properties in pain management. In this study, vulvodynia-like symptoms were induced in female mice using Complete Freund's adjuvant (CFA). After the induction of symptoms, the mice were treated with a combination of Acmella oleracea and Boswellia serrata extracts (AO + BS). Behavioral pain assessments were conducted to monitor the effects of the treatment. Additionally, biochemical and functional evaluations were performed to measure spinal microgliosis and neuronal overexcitation. The combination of Acmella oleracea and Boswellia serrata (AO + BS) resulted in a significant reduction of vulvar hypersensitivity in mice. Besides alleviating pain, AO + BS therapy also reduced spinal microgliosis and neuronal overexcitation in mice with vulvodynia. The findings suggest that the AO + BS combination has the potential to alleviate vulvodynia associated pain through mechanisms involving the reduction of spinal microgliosis and neuronal overexcitation. These results point to the therapeutic promise of these plant extracts for chronic pain conditions like vulvodynia. The combination of Acmella oleracea and Boswellia serrata shows potential as a treatment for vulvodynia. However, further studies are needed to explore the underlying mechanisms and to optimize the dosage for clinical use.

Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review.

Complex regional pain syndrome (CRPS) is a chronic pain condition most often triggered by direct injury to an extremity that is characterized by disproportionate pain, sensory abnormalities, and autonomic dysfunction. Early research into intravenous lidocaine therapy for CRPS has demonstrated promise, but clinical evidence remains scarce. We report on 12 patients with chronic CRPS who underwent intravenous lidocaine therapy and discuss our findings in the context of the existing literature. Patients ages ranged from 25 to 64 years. Duration of CRPS ranged from 4 to 25 years. The majority of patients (8/12, 67%) reported adequate subjective pain relief with intravenous lidocaine therapy, whereas four patients reported inadequate subjective pain relief with therapy. All patients were being treated with at least one other pharmacotherapy. Three patients experienced minor side effects. Our cases, taken with existing evidence, suggest that intravenous lidocaine for the treatment of chronic CRPS is safe and may decrease the pain associated with chronic CRPS. However, this study lacks adequate sample size to make those conclusions confidently. We recommend a randomized placebo-controlled multicenter clinical trial to establish the efficacy and side effect profile of systemic intravenous lidocaine more confidently for the treatment of pain due to chronic CRPS.

Sex Differences in Pain Scores and Medication Consumption for Chronic Non-Cancer Pain.

Chronic pain is defined as any persistent or recurring pain lasting longer than 3 months that significantly affects a person's quality of life. Millions worldwide are impacted by chronic pain, but its subjective nature makes it difficult to quantify and compare between individuals. This retrospective analysis aimed to examine the differences in pain perception and reporting between male and female patients, as well as how their pain was managed. Data from 1995 patients who met the inclusion criteria were selected from the Advocate Illinois Masonic Pain Clinic database. The types of pain assessed in this study included lower back pain, neck pain, and osteoarthritis. The findings indicate that females suffer more from chronic pain conditions than males, where lower back pain had the highest prevalence in both sexes (63.7% reported). Baseline Numeric Rating Scale (NRS) scores at the first inpatient visit were statistically higher in females than males (7.95 ± 1.35 vs. 7.72 ± 1.46, p = 0.006). After 1 year of treatment, both sexes reported a clinical improvement in their symptoms. With regards to medication, females reported a higher use of medications such as muscle relaxants, benzodiazepines, and tricyclic antidepressants, while males reported a higher use of opioids (measured in MMEs). This study reveals a significant sex difference in the reporting of non-cancer-related chronic pain, with females reporting higher pain intensity than males.

Postoperative pain management in patients with preexisting opioid dependence-A scoping review protocol.

Opioid-dependent patients with chronic pain conditions present a significant challenge for anesthesiologists when managing acute postsurgical pain. Opioid-dependent patients can experience tolerance, physical dependence, and hyperalgesia. These patients have an increased risk of poorly managed acute postoperative pain, which can ultimately lead to suffering and potentially an overall increase in length of hospitalization and healthcare cost. However, this is an under-researched field. This scoping review aims to investigate effective strategies in managing postoperative pain in patients with preexisting opioid dependence. A scoping review will be conducted on postoperative pain management in patients with preexisting opioid dependence. This review will be prepared according to the JBI methodology for scoping reviews and to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR). We will conduct a comprehensive search across multiple databases. Backward citation searching of the final included articles will also be conducted. Data extraction will include trial and participant characteristics, intervention details, and reported outcomes. In the final review the results will be presented as a descriptive summary with supplementary tables, figures, and graphs where applicable. The planned scoping review will map out the current evidence about effective strategies to manage postoperative pain in patients with preexisting opioid dependence. We will aim to identify research gaps that can be used as support in the development of further research.

Understanding barriers and facilitators to non-pharmaceutical chronic pain research engagement among people living with chronic pain in the UK: a two-phase mixed-methods approach

ObjectivesChronic pain treatment engagement is dominated by pharmaceutical methods, while previous research has assessed barriers to uptake of non-pharmaceutical treatments, there has not been research one step earlier in the...

Efficacy and safety of antidepressants for pain in older adults: A systematic review and meta-analysis.

In many countries, pain is the most common indication for use of antidepressants in older adults. We reviewed the evidence from randomized controlled trials on the efficacy and safety of antidepressants, compared to all alternatives for pain in older adults (aged ≥65 years). Trials published from inception to 1 February 2024, were retrieved from 13 databases. Two independent reviewers extracted data on study and participant characteristics, primary efficacy (pain scores, converted to 0-100 scale) and harms. Estimates for efficacy were pooled using a random effects model and reported as difference in means and 95% CI. Quality of included trials was assessed using the Cochrane risk of bias tool. Fifteen studies (n = 1369 participants) met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (6/15 studies each). Pain related to knee osteoarthritis was the most studied (6/15 studies). For knee osteoarthritis, antidepressants did not provide a statistically significant effect for the immediate term (0-2weeks), (-5.6, 95% confidence interval [CI]: -11.5 to 0.3), but duloxetine provided a statistically significant, albeit a very small effect in the intermediate term, (≥6weeks and <12 months), (-9.1, 95% CI: -11.8 to -6.4). Almost half (7/15) of the studies reported increased withdrawal of participants in the antidepressant treatment group vs. the comparator group due to adverse events. For most chronic painful conditions, the benefits and harms of antidepressant medicines are unclear. This evidence is predominantly from trials with sample sizes of <100, have disclosed industry ties and classified as having unclear or high risk of bias.

MiR-374 family is a key regulator of chronic primary pain onset.

Chronic primary pain conditions (CPPCs) are linked to catecholamine activation of peripheral adrenergic receptors. Yet, catecholamine-dependent epigenetic mechanisms, such as microRNA (miRNA) regulation of mRNA transcripts, remain largely unknown. We sought to identify RNA species correlated with case status in 3 pain cohorts, to validate RNAs found to be dysregulated in a mouse model of CPPC onset, and to directly test the role of adrenergic receptors in miRNA regulation. Furthermore, we tested antinociceptive effects of miR-374 overexpression. We used RNA-seq and quantitative reverse transcription polymerase chain reaction to measure RNA expression in 3 pain cohorts. Next, we validated identified RNAs with quantitative reverse transcription polymerase chain reaction in a mouse model of CPPC onset, measuring expression in plasma, peripheral (adipose, muscle, dorsal root ganglia [DRG]), and central (spinal cord) tissues. Then, we stimulated adrenergic receptors in primary adipocyte and DRG cultures to directly test regulation of microRNAs by adrenergic signaling. Furthermore, we used in vitro calcium imaging to measure the antinociceptive effects of miR-374 overexpression. We found that one miRNA family, miR-374, was downregulated in the plasma of individuals with temporomandibular disorder, fibromyalgia syndrome, or widespread pain following a motor vehicle collision. miR-374 was also downregulated in plasma, white adipose tissue, and spinal cord from mice with multisite mechanical sensitivity. miR-374 downregulation in plasma and spinal cord was female specific. Norepinephrine stimulation of primary adipocytes, but not DRG, led to decreased miR-374 expression. Furthermore, we identified tissue-specific and sex-specific changes in the expression of predicted miR-374 mRNA targets, including known (HIF1A, NUMB, TGFBR2) and new (ATXN7, CRK-II) pain targets. Finally, we demonstrated that miR-374 overexpression in DRG neurons reduced capsaicin-induced nociceptor activity. Downregulation of miR-374 occurs between adrenergic receptor activation and mechanical hypersensitivity, and its adipocyte source implicates adipose signaling in nociception. Further study of miR-374 may inform therapeutic strategies for the millions worldwide who experience CPPCs.

Pharmacological Treatment of Fibromyalgia Syndrome: A Practice-Based Review.

Fibromyalgia Syndrome (FMS) is a complex chronic pain condition characterized by widespread musculoskeletal pain and numerous other debilitating symptoms. The purpose of this review is to provide a comprehensive overview, based on everyday clinical practice, of the drugs presently employed in the treatment of FMS. The treatment of FMS is based on a multimodal approach, with pharmacologic treatment being an essential pillar. The drugs used include tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, other antidepressants, anticonvulsants, myorelaxants, and analgesics. The effectiveness of these medications varies, and the choice of drug often depends on the specific symptoms presented by the patient. Many drugs tend to either address only some domains of the complex FMS symptomatology or have a limited effect on pain. Each treatment option comes with potential side effects and risks that necessitate careful consideration. It may be beneficial to divide patients into clinical subpopulations, such as FMS with comorbid depression, for more effective treatment. Despite the complexities and challenges, the pharmacological treatment remains a crucial part for the management of FMS. This review aims to guide clinicians in prescribing pharmacological treatment to individuals with FMS.

Sleep and circadian rhythm disturbances as risk and progression factors for multiple chronic overlapping pain conditions: a protocol for a longitudinal study.

Chronic overlapping pain conditions (COPCs), such as chronic low back pain (cLBP) and fibromyalgia, frequently cooccur and incur substantial healthcare costs. However, to date, much focus has been placed on individual anatomically based chronic pain conditions, whereas little is known about the mechanisms underlying progression to multiple (more than 1) COPCs. This study aims to address the gap by investigating the role of common and modifiable risk factors, specifically sleep and circadian rhythm disturbances, in the development of multiple COPCs. The study will enroll 300 participants with cLBP, including 200 with cLBP only and 100 with cLBP plus other COPCs (ie, fibromyalgia, temporomandibular disorders, irritable bowel syndrome, and chronic headaches) and follow them up for 12 months. Sleep and circadian rhythms will be assessed using wireless sleep electroencephalography, 24-hour evaluation of the rhythm of urinary 6-sulfatoxymelatonin, actigraphy, and sleep diaries. Pain amplification using quantitative sensory testing, psychological distress using validated self-report measures, and the number of pain sites using a pain body map will also be assessed. This research aims to (1) comprehensively characterize sleep/circadian disturbances in individuals with single and multiple COPCs using multimodal in-home assessments; (2) examine the associations between sleep/circadian disturbances, changes in pain amplification, and psychological distress; and (3) investigate the relationship among these factors and the progression in the number of pain sites, a proxy for multiple COPCs. The findings will provide insights into the mechanisms leading to multiple COPCs, potentially informing treatment and prevention strategies for these complex conditions.

Complex Regional Pain Syndrome: Diagnosis, Pathophysiology, and Treatment Approaches.

Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by significant sensory, motor, and autonomic dysfunction, often following trauma or nerve injury. Historically known as causalgia and reflex sympathetic dystrophy, CRPS manifests as severe, disproportionate pain, often accompanied by hyperalgesia, allodynia, trophic changes, and motor impairments. Classified into type I (without nerve injury) and type II (associated with nerve damage), CRPS exhibits a complex pathophysiology involving peripheral and central sensitization, neurogenic inflammation, maladaptive brain plasticity, and potential autoimmune and psychological influences. The diagnosis relies primarily on clinical evaluation using criteria such as the Budapest Criteria, supported by supplementary tests to exclude differential diagnoses. However, its overlapping features with other conditions complicate diagnostic accuracy. The management of CRPS necessitates a multidisciplinary approach combining physical therapy, psychological support, and pharmacotherapy. Physical therapies, including graded motor imagery and mirror therapy, are essential for preserving function and preventing complications. Pharmacological treatments target neuropathic pain and inflammatory components, utilizing agents such as gabapentinoids, corticosteroids, and bisphosphonates. In refractory cases, interventional modalities like spinal cord stimulation and dorsal root ganglia stimulation provide promising options, although their efficacy remains variable. Emerging therapies, such as immune-modulatory treatments and advanced neuromodulation techniques, reflect the ongoing pursuit of effective interventions. This review synthesizes current knowledge, providing insights into diagnostic frameworks, pathophysiological mechanisms, and evolving treatment strategies to improve outcomes for individuals affected by CRPS.

The Antinociceptive Effects and Sex-Specific Neurotransmitter Modulation of Metformin in a Mouse Model of Fibromyalgia.

Fibromyalgia (FM) is a chronic and debilitating condition characterized by diffuse pain, often associated with symptoms such as fatigue, cognitive disturbances, and mood disorders. Metformin, an oral hypoglycemic agent, has recently gained attention for its potential benefits beyond glucose regulation. It has shown promise in alleviating neuropathic and inflammatory pain, suggesting that it could offer a novel approach to managing chronic pain conditions like FM. This study aimed to further explore metformin's analgesic potential by evaluating its effects in an experimental FM model induced by reserpine in both male and female mice. After the administration of 200 mg/kg metformin to male and female mice, the FM-related symptoms were assessed, including mechanical allodynia, thermal hyperalgesia, and depressive-like behaviors. A histological examination of the thalamus, hippocampus, and spinal cord was conducted using haematoxylin and eosin staining. The neurotransmitter and proinflammatory cytokines levels were measured in the brains and spinal cords. Our results have shown that metformin treatment for seven days significantly reversed these FM-like symptoms, reducing pain sensitivity and improving mood-related behaviors in both the male and female mice. Additionally, metformin exhibited neuroprotective effects, mitigating reserpine-induced damage in the hippocampus, thalamus, and spinal cord. It also significantly lowered the levels of the proinflammatory cytokine interleukin 1-beta (IL-1β) in the brain and spinal cord. Notably, metformin modulated the neurotransmitter levels differently between the sexes, decreasing glutamate and increasing serotonin and norepinephrine in the male mice, but not in the females. These findings underscore metformin's potential as an alternative therapy for FM, with sex-specific differences suggesting distinct mechanisms of action.

PDGFR-α Mediated the Neuroinflammation and Autophagy via the JAK2/STAT3 Signaling Pathway Contributing to Depression-Like Behaviors in Myofascial Pain Syndrome Rats.

Depression often occurs in patients with additional co-morbidities, particularly in cases of chronic pain. Currently, there is a lack of research on the molecular mechanisms of depression under chronic pain conditions and suitable animal models. Due to the contradiction exhibited by platelet-derived growth factor receptor (PDGF/PDGFR) in neuroprotection, further investigation is required. In the present study, we investigated the roles of PDGFR-α in the hippocampus based on rat models of chronic pain (myofascial pain syndrome, MPS) that exhibited depressive phenotypes. The depression-like phenotypes were assessed by the sucrose preference test, forced swimming test, tail suspension test, and the levels of BDNF and 5HT1AR. Electron microscopic analysis and altered expression of autophagy-related proteins revealed reduced autophagy levels in the hippocampus of MPS rats. Phosphorylation PDGFR-α was significantly upregulated in the MPS rat model of depression, as well as the levels of inflammatory factors and p-JAK2/p-STAT3. Treatment with inhibitors of PDGFR-α or JAK2/STAT3 alleviated depressive behaviors, Nissl bodies staining, increased the protein levels of BDNF and 5HT1AR, and decreased the levels of inflammatory factors in MPS rats. Additionally, it restored autophagy levels. These results indicate that PDGFR-α induces neuroinflammation, altered autophagy, and depressive behavior, potentially mediated by the JAK2/STAT3 signaling pathway in MPS rats. PDGFR-α may thus represent a promising therapeutic target for the treatment of this type of depression.

A Mendelian randomization study finds no evidence for causal effects of C-reactive protein (CRP) on chronic pain conditions.

This two-sample Mendelian randomization study examined causal associations of C-reactive protein (CRP) with spinal pain, the extent of multisite chronic pain, and chronic widespread musculoskeletal pain. No causal associations were found between CRP and these pain conditions.

Managing acute jaw trauma in the emergency and urgent care clinics

Chronic pain conditions constitute the primary reason for seeking healthcare, the development of related disability and addiction, and the highest driver of healthcare costs. Chronic temporomandibular, jaw and orofacial pain after acute jaw sprain/strain can be prevented if prompt and appropriate treatment in an emergency or urgent care clinic is provided using a jaw sprain/strain clinical protocol immediately after onset to begin the healing and recovery process. If pain does persist beyond a few weeks, a delayed-recovery protocol can be helpful. The rationale and strategies for both are discussed.

Love Thy Neighbor? Exploring Gastroenterology Attitudes Toward Endometriosis Screening.

Endometriosis is a chronic painful condition affecting 10% of reproductive-aged women with a high prevalence of overlapping gastrointestinal symptoms. There is a significant diagnostic delay for endometriosis and current screening practices for endometriosis in gastroenterology clinic populations have not been evaluated. 112 gastroenterology providers (57.5% females, 64.3% physicians) completed an anonymized exploratory survey (40.1% response rate). Most respondents (59.4%) currently do not screen for endometriosis, but the majority (72.1%) reported they would be "extremely likely" or "somewhat likely" to screen for endometriosis after being presented with data on the high prevalence of chronic GI symptoms in patients with endometriosis.