Complementary therapies for chronic knee pain: A placebo-controlled RCT of Reiki and mindfulness.

Risks for Adverse Events by Sex and Age After Prescription Opioid Dose Reduction: A Secondary Analysis Across 8 U.S. Health Systems.

Glycyrrhiza uralensis Fisch: A novel source of analgesic activity through NaV1.8 sodium channel modulation.

The sphenopalatine ganglion as a target in interventional pain therapy

Background. Systematic reviews are essential tools for evidence-based practice but are often time-consuming. Recent developments in artificial intelligence, including large language models such as ChatGPT-4o, offer potential to support and partially automate some processes. This study aimed to evaluate the performance of ChatGPT-4o in assessing Risk of Bias (RoB) using RoB 2.0 tool and in extracting data from randomised controlled trials (RCTs) on exercise therapy for chronic low back pain. Materials and Methods. This cross-sectional comparative study included 150 RCTs previously assessed by human reviewers. ChatGPT-4o was tested in two tasks: (1) RoB assessment using a single structured prompt, compared with expert ratings across five domains and overall judgement; (2) data extraction across 34 predefined variables using both simplified and detailed prompts. Human reviewers served as the reference standard. Statistical analysis focused on Cohen’s kappa and overall accuracy, alongside sensitivity, specificity, PPV, NPV, and F1-score. Results. Agreement between ChatGPT-4o and human reviewers for RoB assessment was low (Cohen’s κ = 0.14), with a tendency to underestimate bias. Sensitivity was 40%, while specificity and PPV were higher for low-risk classifications. For data extraction, ChatGPT-4o showed strong performance, with accuracy above 84% and F1-scores over 90% using both prompt types. Hallucinations were rare (<0.02%). Task duration was reduced from 30-50 minutes (human reviewers) to under 5 minutes with ChatGPT-4o. Conclusions. While ChatGPT-4o showed limited reliability for RoB assessment, likely due to the interpretative complexity of the task, it performed robustly in data extraction, particularly when guided by well-structured prompts. Its high precision, speed, and low hallucination rate suggest strong potential as a secondary reviewer in systematic review workflows. Nonetheless, its application to evaluative tasks requiring critical judgement remains premature. With further development and proper human oversight, LLMs like ChatGPT-4o may help streamline systematic review processes, especially for labour-intensive, structured data extraction.

Peripheral Nerve Stimulation to the Transverse Abdominis Plane as Therapy for Refractory Abdominal Pain: A Case Series of Two Patients

Acute respiratory infections are a heterogeneous group of diseases that combine damage to both the upper (in most cases) and lower respiratory tract. The incidence of this pathology and the number of visits to doctors and economic losses tend to increase annually. Strains of pathogens with pronounced pathogenicity and having mechanisms of "hiding" from the immune response of the human body play a significant role in the deterioration of the epidemiological situation. Increasingly, there are blurred and atypical clinical pictures of acute respiratory pathology, which complicate the etiological diagnosis and, accordingly, adequate treatment. The problem of unjustified prescription of antibacterial therapy in the case of viral etiology of the process remains difficult and urgent, as a result of which there is an increase in antibiotic resistance of pathogens. Many patients underestimate the importance of pathogenetic and symptomatic therapy. The article discusses the issues of modern diagnosis and therapy of patients with acute diseases of the upper respiratory tract, the role and place of the systemic nonsteroidal anti-inflammatory drug loxoprofen in such patients.

Extracorporeal shockwave therapy (ESWT) has been used successfully in the musculoskeletal field (traumatology and orthopedics) for decades, with adistinction being made between radial and focused ESWT, each with its own different properties. Low back pain is awidespread health problem around the world, especially in industrialized countries. Around 80% of all people suffer from low back pain at least once in their lives. Depending on the study, myofascial pain syndromes are acommon cause of back pain in 67-100% of patients. The facet joints of the lumbar spine and the sacroiliac joint each contribute to around one third of chronic low back pain. An increasing number of studies are investigating the treatment and diagnosis of low back pain using ESWT, with aparticular focus on the treatment of facet joints, myofascial pain syndromes, trigger points, and the SI joint. ESWT is effective in relieving pain and improving functional outcomes in patients with chronic low back pain and is asimple and safe procedure with no relevant side effects.

G protein-coupled receptors (GPCRs) and TRPV (transient receptor potential vanilloid) channels are crucial for signal transduction in physiological processes, including neurotransmission, pain, and itch. Downstream effectors of GPCR signaling can directly stimulate TRPV channels or enhance their sensitivity to stimuli, a process known as TRPV sensitization. Traditionally, GPCRs are activated at the cell surface by extracellular agonists, triggering signaling cascades. Recent evidence suggests GPCRs continue to signal from intracellular organelles. The human Mas-related G-protein coupled receptor X1 (MrGPRX1) is a GPCR expressed in primary sensory neurons involved in nociception and pruritus. Recent studies demonstrated how intracellular GPCR signaling regulates neuronal activity. However, there is no evidence characterizing MrGPRX1 trafficking or intracellular signaling. Herein, we characterized MrGPRX1 signaling within the endosomal network and its role in sensitizing TRPV1 channels to enhance itch signaling. Utilizing subcellular targeted biosensors, we demonstrated MrGPRX1 can traffic and signal from endosomes. Immunofluorescence analysis showed that MrGPRX1 internalizes following BAM8-22 stimulation. BRET assays revealed that MrGPRX1 activation induces Gαqand β-arrestin-1 recruitment to the plasma membrane and early endosomes. Inhibition of dynamin or clathrin blocked BAM8-22-induced MrGPRX1 endocytosis and decreased nuclear extracellular signal-regulated kinase (ERK) signaling. Calcium signaling confirmed that MrGPRX1-mediated TRPV1 sensitization is mediated by protein kinase C and ERK activation. Our findings reveal a novel role for MrGPRX1 endosomal signaling in TRPV1 sensitization.Understanding the mechanisms of MrGPRX1 signaling offers valuable insights into differentiating between pain and itch pathways, aiding in the development of targeted therapies for chronic pain and persistent itch.

To evaluate the relationship between pain catastrophizing, treatment modality, pain intensity, and functional disability in patients with chronic lower back pain, while also accounting for the effects of kinesiophobia and self-efficacy using generalized linear mixed models. Secondary analysis of a randomized controlled trial. Outpatient clinical setting. Forty-eight adults with chronic low back pain participated in the study. Participants were randomized into three intervention groups receiving therapeutic exercise (ET) either alone, combined with manual therapy (ETmanualtherapy), or with kinesiotape (ETkinesiotape). Each group underwent two sessions per week for 12 weeks. Disability, pain intensity, kinesiophobia, pain catastrophizing, and self-efficacy were assessed at baseline, 3, 6, and 12 weeks. Generalized linear mixed models revealed a significant reduction in pain over time in all intervention groups (p < 0.001). A significant interaction was identified between the treatment group and catastrophizing levels (p = 0.023), with the Kinesiotape group being the only one showing increased pain scores associated with higher PCS levels. Regarding disability, significant effects were found for catastrophizing (p = 0.015), kinesiophobia (p < 0.001), and self-efficacy (p = 0.008), as well as a significant interaction between the group and self-efficacy (p = 0.003). In the groups without kinesiotaping, lower self-efficacy was associated with increased disability; however, this pattern was not observed in the kinesiotape group. The study found that pain and disability improved over time in all the intervention groups. However, psychological factors influenced outcomes differently depending on the treatment, with catastrophizing increasing pain only in the kinesiotape group. Thus, kinesiotaping may offer a protective effect by modulating psychological influences in chronic lower back pain.Trial registration NCT05544890

Chronic and neuropathic pain remain significant clinical challenges owing to limited efficacy and safety concerns associated with conventional analgesics, including opioids and NSAIDs. Voltage-gated sodium channels, particularly Nav1.7 and Nav1.8, have emerged as promising non-opioid targets for pain modulation, given their selective expression in peripheral nociceptors and critical roles in pain signal transmission. Recent advances in structural biology and pharmacology have enabled the development of highly selective inhibitors targeting these channels. This review explores sodium channel inhibitors currently in clinical development, with a focus on suzetrigine (VX-548), the first US Food and Drug Administration (FDA)-approved Nav1.8 inhibitor for acute pain, as well as other investigational agents such as ralfinamide, OLP-1002, LTGO-33 and HBW-004285. Despite setbacks in early candidates owing to selectivity and tolerability issues, ongoing trials demonstrate renewed optimism for a new class of analgesics that may overcome the limitations of traditional pain therapies. We discuss key pharmacological challenges observed in earlier trials including functional redundancy, species differences, and on-target side effects, and outline how emerging strategies, such as structural biology-guided design, combination therapies, and precision medicine, are paving the way for safer, more effective, nonaddictive pain treatments.

Efficacy of non-pharmacological therapies in chronic pelvic pain of endometriosis: a systematic review and meta-analysis.

Background: Pulsed radiofrequency (PRF) applied to the dorsal root ganglion (DRG) has been proposed as an effective neuromodulator treatment for persistent radicular pain. Autologous conditioned serum (ACS) therapy, derived from the patient’s own blood, offers a conservative approach. This study aims to evaluate the efficacy of ACS applied to the DRG as an adjunct in treating lower limb radicular pain (LLRP). Methods: A prospective, randomized, double-blind, placebo-controlled clinical trial was conducted comparing PRF combined with ACS versus PRF with physiological saline (PhS) on the DRG. Seventy patients (35 per group) with radicular pain lasting ≥6 months and refractory to previous treatments were enrolled. The primary outcome measure was the Numeric Pain Rating Scale (NPRS); secondary measures included the Oswestry Disability Index (ODI), Mood Assessment Scale (MOAS), SF-12 quality of life questionnaire, and DN4 neuropathic pain scale. Assessments occurred at baseline, 1 month, 3 months, 6 months, and 12 months post-intervention. Results: A total of 70 patients were included. The ACS group showed a significant reduction in pain compared to controls at 30 days (p < 0.05). Additionally, neuropathic symptoms such as tingling, numbness, stubbing, and burning decreased significantly in the ACS group during this period (p < 0.05). While both groups experienced pain reduction over time, no significant differences persisted at 6 months. No adverse effects were reported. Conclusions: The addition of ACS to PRF provides a short-term, statistically significant reduction in radicular pain at 30 days, suggesting it is a safe and effective adjunct therapy for lower limb radicular pain.

BACKGROUND: Neck pain, commonly treated by physical therapists, can be a symptom of head and neck cancers. Adequate screening is essential to recognize the need for referral when accompanied by symptoms of a nonmusculoskeletal nature. CASE PRESENTATION: A 65-year-old male was referred to physical therapy for chronic neck pain. Radiographs showed moderate to severe degeneration of the lower cervical spine. He demonstrated significant spinal range of motion restrictions, negative neurological screening, and symptoms of dysphagia and hoarseness. OUTCOME: The patient was referred back to his provider following the physical therapy evaluation due to concomitant symptoms of dysphagia and hoarseness. Succeeding onset of a neck mass, a syncopal episode and pain with swallowing warranted further testing, including computed tomography, fine-needle aspiration, and direct tissue biopsy, ultimately leading to the diagnosis of laryngeal cancer. He was referred to oncology and began chemotherapy and radiation treatment. DISCUSSION: This case highlights the role physical therapists must play in assisting with diagnosis of red flag conditions. JOSPT Cases 2025;5(4):1-5. Epub 17 October 2025. doi:10.2519/josptcases.2025.0188

Addressing chronic pain and suicide risk using Mindfulness-Based Cognitive Therapy: Rationale, design and baseline characteristics.

The perception of pain varies rhythmically across the day. Although early studies showed variations in pain sensitivity, mechanistic studies are only now identifying how clock genes and individual rhythms affect pain outcomes. Core clock genes, including Bmal1 and Cry1, regulate pain through neuroimmune interactions, providing potential biomarkers to understand individual variability. This rhythmicity offers a promising avenue for a precision medicine approach to identify optimal timing for pain therapies and stratification of individuals. Integrating daily rhythmic patterns with digital health tools could significantly enhance treatment strategies, moving beyond the conventional "one-size-fits-all" approach toward personalized pain management.

Currently, there are no quantitative pain biomarkers mechanistically assessing the nociceptive system function or analgesic efficacy, which is crucial for developing personalized pain therapies. This lack of specific biomarkers is likely a significant factor in the failure to develop new targeted pain management strategies, potentially leading to the overuse of opioids in chronic pain. Two methodologies-patient-reported outcomes and quantitative sensory testing-offer potential clinical markers that could help close these gaps. This brief review will discuss the strengths and weaknesses of both approaches as well as their implications for the future.

BackgroundPhysical therapy is routinely recommended for knee pain attributed to a degenerative meniscal tear, but its efficacy has not been established.MethodsWe randomly assigned participants 45 to 85 years of age with knee pain, osteoarthritis, and meniscal tear to one of four groups: home exercise (3-month home-exercise program), home exercise plus text messages to encourage exercise adherence, home exercise plus text messages plus sham physical therapy (in-clinic sham manual therapy and sham ultrasound therapy), and home exercise plus text messages plus standard physical therapy (supervised strengthening, functional, and stretching exercises and manual therapy). The primary outcome was the change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain subscore (range, 0 to 100, with higher scores indicating more pain) between baseline and 3 months, with adjustment for trial site, baseline KOOS pain subscore, and radiographic grade.ResultsA total of 879 participants underwent randomization (mean [±SD] age, 59.2±7.8 years). The difference in the 3-month change in the KOOS pain subscore between home exercise and home exercise plus text messages was −0.1 points (98.3% confidence interval [CI], −3.8 to 3.7) and between home exercise and home exercise plus text messages plus standard physical therapy was 2.5 points (98.3% CI, −1.3 to 6.2); the difference between home exercise plus text messages and home exercise plus text messages plus standard physical therapy was 2.5 points (98.3% CI, −1.4 to 6.5). Adverse events were generally nonserious and evenly distributed overall across groups.ConclusionsFor patients with degenerative meniscal tear and knee pain, the addition of physical therapy or text messages to encourage adherence to home exercises was not superior in reducing pain to a home-exercise program alone. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and others; TeMPO ClinicalTrials.gov number, NCT03059004.)

Neuropathic pain (NP) is one of the most devastating and under-managed symptoms of multiple sclerosis (MS). As it stands, NP is a difficult condition to treat, as many commonly used pain therapies are ineffective. Research has now emerged demonstrating sex differences in the mechanism of NP in MS, adding complexity to the search for new treatments. Although it is widely known that female patients are more likely than male patients to develop MS, it is less commonly acknowledged that they are also more likely to experience NP in the disease. Thus, there is an urgent need to develop NP treatments specifically for female patients with MS. Using the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, we have characterized the outgrowth in culture as well as the spinal innervation pattern of peptidergic primary sensory afferents in both sexes. We then used a receptor antagonist to disrupt neuropeptide signaling from these cells to treat pain. We found structural plasticity in peptidergic nociceptors from female animals with established EAE both in vitro and in vivo, as well as increased antibody stain intensity for the neuropeptide calcitonin gene-related peptide (CGRP). Using a receptor antagonist for CGRP (CGRP8-37), we were able to reverse spontaneous pain in female EAE animals. These results suggest that targeting peptidergic nociceptors and CGRP signaling, specifically in female patients, may be a viable strategy to relieve and possibly reverse pain in female patients with MS.

Abstract This study analyzed the efficacy of acceptance and commitment therapy (ACT) in six individuals with chronic low back pain plus depressive symptoms using an idiographic approach within a randomized controlled trial. Daily ecological momentary assessments (EMA) and full assessments at baseline, posttreatment, and follow-up were collected. Outcomes included pain interference, pain intensity, and depressed mood, and the process variable was psychological inflexibility. Analyses involved visual inspection, non-overlap of all pairs, Tau, Tau-U, and idiographic network analysis. Moderate improvements were observed in pain interference (5/6), depressed mood (5/6), and psychological inflexibility (3/6), with limited change in pain intensity (1/6). Most participants (4/6) reported an overall relevant improvement. Idiographic networks showed considerable variability across participants, with psychological inflexibility and depressed mood playing a central role. Findings suggest ACT may help reduce pain interference and depressed mood, highlighting the need for personalized approaches and the continued use of single-case methods combined with EMA.