A compound paradox has been identified in the revised (2020) International Association for the Study of Pain (IASP) definition of pain, such that it simultaneously prescribes a connection between pain and tissue damage and allows that prescription to be violated. In a narrative form, the objective of this paper is to reveal these paradoxes and to offer a pathway to their resolution, thus clarifying the definition of pain for the purposes of scientific study and clinical application. The first paradox is that contradictory true positions can be held, when the experiencer claims to be "in pain" and the observer cannot find the required association with tissue damage or, preferably as is argued, nociception. The second paradox is revealed by the construct of "nociplastic" pain, which contradicts the IASP definition to the extent that nociceptors have not been activated, yet at the same time is consistent with that definition to the extent that it "resembles" an experience associated with actual or potential tissue damage. In the interests of all concerned parties, the IASP definition of pain can be strengthened by removing the current ambiguity of interpretation, grounding the experience in a reconceptualisation of nociception as activation of a nociceptive apparatus, and clearly distinguishing it from suffering.
There is converging evidence that indicates that the nucleus accumbens (NAc) plays a substantial role in pain modulation and analgesic drug responses. Here, the role of the NAc dopaminergic signaling in the development of morphine tolerance in a rat neuropathic pain model was explored. Morphine tolerance was induced by twice daily administration of intrathecal morphine in spinal nerve-ligated animals. The extracellular dopamine level in the NAc was measured by microdialysis study and the effects of dopaminergic receptor agonists microinjected into the NAc on morphine analgesic tolerance were evaluated behaviorally. Using immunohistochemical techniques, dopaminergic fiber expression in the NAc was assessed. Additionally, the effects of microglial inhibitor minocycline on the extracellular dopamine level in the NAc and the development of morphine tolerance were investigated. Microdialysis study demonstrated that the extracellular level of dopamine in the NAc was decreased in morphine tolerant animals. A dopaminergic D1- or D2-like receptor agonist pretreated into the NAc improved analgesic response to morphine in the tolerant animals. By pretreating a microglial inhibitor minocycline with daily morphine administration, the level of extracellular dopamine in the NAc was partially recovered and the development of morphine tolerance was attenuated. These observations indicate that the decreased dopaminergic neurotransmission in the NAc induced by microglial activation plays a significant role in the development of morphine tolerance. By delineating how alterations in dopamine transmission and related neuroadaptations within the NAc contribute to diminished opioid efficacy, future studies may identify novel molecular and cellular targets for therapeutic intervention.
Postherpetic neuralgia (PHN) is persistent pain that occurs after the resolution of skin lesions caused by the reactivation of the herpes zoster virus. Several first-line agents, including anticonvulsants, tricyclic antidepressants, and lidocaine patches, are used in treatment. However, systematic, evidence-based, multidisciplinary clinical practice guidelines (CPGs) addressing the use of opioids and pain interventions-such as nerve blocks-for patients with refractory PHN unresponsive to first-line agents have not yet been established. Therefore, the Korean Pain Society, in collaboration with relevant medical specialty societies, has developed de novo CPGs for the management of refractory PHN. The development process followed Cochrane's systematic literature review methodology and employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the certainty of evidence and strength of recommendations. Key questions, identified through a survey of experts treating patients with refractory PHN, were finalized by the CPGs development panel. A literature search was conducted in four electronic databases: PubMed (MEDLINE), Embase, Cochrane Library, and KoreaMed. Studies were selected based on predefined inclusion and exclusion criteria using the population, intervention, comparison, outcomes, and study design (PICOS) framework. The resulting recommendations integrate evidence from the literature with patient and clinician preferences and values. They also take into account the quality of evidence, the balance of benefits and harms, potential barriers to implementation, and feasibility within various healthcare settings. These evidence-based multidisciplinary CPGs are expected to assist physicians in safely and effectively treating patients with refractory PHN.
Pulsed radio frequency (PRF) is a novel therapeutic method for treating neuropathic pain (NP). This study aimed to elucidate the role of NF-E2-Related Factor 2 (Nrf2) in pain signal transduction associated with the mechanism of PRF analgesia action. Establishing the spared nerve injury (SNI) rat model and PRF treated model (45 V5 minutes, 45 V15 minutes, 90 V15 minutes), the authors used behavioral testing, western blotting, and enzyme-linked immunosorbent assay methods to verify the analgesic effect of PRF. Secondly, behavioral testing and biomarker analyses were performed in SNI rats that received intrathecally injected calmodulin-dependent protein kinase type II (CaMKII) antagonist, calcitonin gene-related peptide (CGRP) antagonist, or Nrf2 activator. High-voltage, long-duration PRF significantly alleviated mechanical hypersensitivity in SNI rats. On the 9th day after PRF therapy, Nrf2 and heme oxygenase 1 (HO-1) expression were markedly upregulated, otherwise, CaMKII, phosphorylated level of CaMKII (p-CaMKII), NF-kappa B (NF-κB) p65, and CGRP content were downregulated. Otherwise, intrathecal CaMKII antagonist, CaMKII, p-CaMKII expression, and CGRP content were decreased. Intrathecal Nrf2 activator led to overexpression of Nrf2, while the expression of p-CaMKII, CaMKII, NF-κB p65, and CGRP content were significantly reduced. Additionally, administration of intrathecal CGRP antagonist decreased CGRP content. After the intrathecal injection of these three drugs, the SNI rats' mechanical hypersensitivity was ameliorated. A novel therapeutic method employing high-voltage, long-duration PRF markedly ameliorated neuropathy, relieving central sensitization by activating the Nrf2 expression-regulated CaMKII/NF-κB signaling pathway blocking Ca2+ pain signal transmission.
The signaling pathways of inflammatory pain are widely explored, but practical clinical approaches to ameliorate pain remain inadequate. Quantitative PCR (qPCR) and ELISA methods were applied to measure the concentration of interleukin (IL)-27 in the inflammatory pain mouse model. Flow cytometry was conducted to identify the source of IL-27. Bone marrow-derived macrophages were stimulated by IL-27, IL-4, lipopolysaccharide, and/or interferon-gamma, followed by qPCR to assess pro-inflammatory and pro-resolving markers' dynamic expression. Then, the molecule profiling of IL-27-primed macrophages was determined using transcriptomic and proteomic sequencing. The Agilent Seahorse XF analyzer calculated energy metabolism indicators. The adoptive cell transfer method was used to verify that forkhead box class O3 (FoxO3) mediates alternatively activated macrophage differentiation induced by IL-27-Ucp2, contributing to alleviating pain sensation in mice. IL-27 is highly expressed centrally and peripherally in rodent pain models. Selective downregulation of IL-27 intensifies pain sensitivity in mice. In macrophages, IL-27 promotes the secretion of anti-inflammatory molecules, such as Arginase-1. Further, transcriptome, energy metabolic examination, and proteome analyses identified that IL-27 restructures the metabolism in macrophages, which is mediated by uncoupling protein 2 (Ucp2) and subsequently activates transcription factor FoxO3. Conditional knockdown of FoxO3 (si-FoxO3) in macrophages refrains the production of anti-inflammatory genes in vitro; meanwhile, adoptive transfer of macrophages with si-FoxO3 but no wild-type macrophages (or IL-27 primed macrophages) prolongs mechanical hyperalgesia in mice. These findings reveal that the IL-27-Ucp2-FoxO3 axis regulates macrophage plasticity distinct from the canonical IL-4-mediated pathway through metabolic rewiring and facilitates alleviating Inflammatory pain.
This up-to-date review focused on the recent advances in the concept, interrelationship, and mechanisms of the polytrauma clinical triad (PCT), and intervention knowledge and approaches to its prevention and treatment from the perspective of military pain medicine, hoping to provide a scientific basis and reference of PCT. Many soldiers suffering from chronic pain coexist with post-traumatic stress disorder and traumatic brain injury. If the above three diseases exist, it is called PCT. Three diseases in this common triad are interrelated and reinforce each other. This triad is challenging to treat and often leads to chronic issues, especially if not adequately monitored and managed. Although each disease of this triad could occur in isolation, it is valuable to know whether the rest of PCT needs to be screened. Current treatment of this triad emphasizes accurate identification and assessment of each disease, the new interdisciplinary and multimodal system of care, individualized customization principles, and shared medical decisions. To maximize clinical success and military service, interdisciplinary providers may benefit from the joint development of complementary treatment and biopsychosocial approach supported by theoretical and empirical evidence. The management of the PCT should emphasize integrative medicine and new interdisciplinary, multimodal nursing. Furthermore, cognitive behavioral therapy, standard rehabilitation care, and integrated health therapy have yielded valuable efficacy. It also should encourage the establishment of harmonious treatment relationships, shared medical decisions, and individualized customization principles to care for military service members with these comorbidities.
The brachioradialis (BR) muscle is a long, large, fusiform muscle on the lateral side of the forearm. It originates from the lateral distal humerus and inserts to the base of the styloid process of the radius. The function of the BR muscle is to flex the elbow, especially with the hand in a neutral position, to pronate and supinate the forearm, and to support wrist extension, especially gripping or picking up something. BR muscle pain arises from repetitive overuse, sudden overloading, and direct blow. Common painful daily activities include putting a cup back down after drinking, opening doors, shaking hands, and using a screwdriver or hammer. The two most common symptoms of BR muscle pain are a sharp and shooting pain during activity and an aching pain at rest from the lateral elbow through the forearm, back of the hand, and thumb and index finger, as well as tightness. Differential diagnosis considers lateral epicondylitis (tennis elbow), radial tunnel syndrome, de Quervain's tenosynovitis, carpal tunnel syndrome, trigger thumb, writer's cramp, and cervical radiculopathy. BR muscle pain is common in patients with subacromial impingement syndrome. Basic conservative treatment includes rest, ice, compression, and elevation (RICE), as well as medication. Stretching exercise for the BR muscle is helpful. Injection techniques, such as myofascial injection or botulinum muscle injection, are also recommended. BR muscle pain is one of the common sources of underdiagnosed and misdiagnosed forearm pain.
Neuropathic pain (NP), a disabling chronic condition with limited treatments, is recapitulated in the chronic constriction injury (CCI) rat model. The role of the miR-1249-3p/VEGFA (vascular endothelial growth factor A) axis in propofol-mediated analgesia remains unclear. AntagomiR-1249-3p, antagomiR-NC (negative control), a VEGFA-targeting siRNA, and si-NC were delivered intrathecally via lentiviral vectors 3 days before CCI. Propofol (15 mg/kg) was intraperitoneally administered for 7 consecutive days after CCI surgery. Behavioral tests assessed mechanical pain threshold and thermal pain threshold (n = 8). Spinal miR-1249-3p and VEGFA expression were detected by reverse transcription-quantitative polymerase chain reaction. Concentrations of tumor necrosis factor-α, interleukin (IL)-6, IL-1β, and IL-18 in the spinal cord were quantified using ELISA. Protein levels of VEGFA, COX2, iNOS, phospho-NF-κB p65, and total NF-κB p65 were detected using Western blotting. The relationship between miR-1249-3p and VEGFA was validated by dualluciferase reporter assay. The expression of miR-1249-3p decreased and VEGFA increased in the spinal cord of CCI rats (all P < 0.001). The luciferase reporter assay demonstrated that miR-1249-3p targets VEGFA (P < 0.001). Propofol treatment upregulated miR-1249-3p (P < 0.001) and downregulated VEGFA (P < 0.001). The antinociceptive effects and suppression of pro-inflammatory markers of propofol were abolished by antagomiR-1249-3p (P < 0.001), and this abolition was rescued by VEGFA knockdown (P < 0.001). Propofol attenuates NP and neuroinflammation in CCI rats via inhibiting the NF-κB pathway through the miR-1249-3p/VEGFA axis. These findings suggest that propofol may reduce behavioral signs of NP and suppress associated neuroinflammation in CCI rats by the miR-1249-3p/VEGFA axis.
This study examined the validity of the EuroQol-5 Dimension 5-Level (EQ-5D-5L) pain/discomfort dimension for acute postoperative pain assessment. This retrospective study analyzed prospectively collected data from the Korean Enhanced Recovery After Surgery (K-ERAS) registry, including adults undergoing elective minimally invasive colorectal cancer surgery at a single tertiary center between October 2023 and December 2025. Convergent validity was assessed using Spearman correlations between the EQ-5D-5L pain/discomfort dimension and numeric rating scale (NRS) scores at rest and during coughing on postoperative days (PODs) 1-3. Correlations with other EQ-5D-5L domains were compared using Steiger's Z-test. Known-group validity was evaluated by area under the curve analysis for discrimination between adjacent levels and by comparisons between ERAS and conventional groups using cumulative link mixed models. Responsiveness was assessed using standardized response means. A total of 333 patients were included. The pain/discomfort dimension demonstrated moderate correlations with NRS scores at rest (ρ = 0.44-0.53) and during coughing (ρ = 0.50-0.57) across PODs 1-3 (all P < 0.001), and showed stronger associations with other EQ-5D-5L dimensions than the NRS. It exhibited acceptable discriminative ability without meaningful floor or ceiling effects and responsiveness comparable to the NRS. The dimension also successfully differentiated clinical groups, with lower pain levels observed in the ERAS group. The EQ-5D-5L pain/discomfort dimension has potential as a valid and responsive measure for acute postoperative pain, complementing numeric scales by capturing the functional impact of pain. Further validation in diverse surgical populations is warranted.
Antiepileptic drugs have shown promise in treating acute nociceptive pain. Bioisosterism is a crucial strategy in analgesic development, enabling molecular modifications that improve therapeutic efficacy and safety. This study aims to develop and evaluate new compounds based on the concept of bioisosterism, synthesizing organocomplexes derived from compounds with established analgesic properties. A novel prototype, Zn(Valp)2Bipy was synthesized, characterized, and tested for antinociceptive and toxicological effects in mice. The compound was administered orally at different doses to evaluate inhibition of acetic acid-induced abdominal constrictions and both phases of the formalin test. Additional evaluation included hot plate and tail immersion assays for central antinociception, the open field test for motor coordination, and a 14-day regimen for subacute toxicity. Zn(Valp)2Bipy (0.1, 1, and 10 mg/kg) significantly reduced abdominal constrictions and licking time in both phases of the formalin test. In the hot plate and tail immersion tests, this treatment significantly increased the latency period, indicating enhanced pain tolerance. Notably, the analgesic effect observed in the hot plate test was reversed by naloxone, suggesting an opioid-like action. Furthermore, in the open field test, the treatment did not affect the animals' motor function. When administered daily at a dose of 1 mg/kg for 14 days, the compound exhibited no observable toxicity, underscoring its safety profile. Zn(Valp)2Bipy demonstrated significant antinociceptive activity through central and peripheral mechanisms without detectable toxicity. This study provides the first evidence of analgesic potential for this complex, highlighting it as a promising drug prototype for effective pain management therapies.
Inadequate pain control after robot-assisted laparoscopic radical prostatectomy (RALP) can impair recovery and quality of life. The acetaminophen/ibuprofen combination is a useful component of opioid-sparing analgesia, but the optimal timing of administration remains unclear. This study aimed to compare preemptive and preventive administration of this combination in RALP patients. Adult patients undergoing RALP under general anesthesia were enrolled. Patients were randomized in a 1:1 ratio to receive acetaminophen 1,000 mg and ibuprofen 300 mg in 100 mL solution either before incision (preemptive group) or at the end of surgery (preventive group). The primary outcome was cumulative fentanyl consumption via intravenous patient-controlled analgesia within 24 postoperative hours. Postoperative pain intensity was assessed using the 11-point numeric rating scale, and the Korean version of the Quality of Recovery-15 questionnaire (QoR-15K), liver function tests, and renal function tests were evaluated. Of 154 patients enrolled, 152 were included in the final analysis. Cumulative fentanyl consumption within 24 hours did not differ significantly between the preemptive and preventive groups (260 μg vs. 320 μg; median difference -60 μg (95% confidence interval [CI] -140 to 60), P = 0.409). Pain scores were generally comparable, but at 48 hours postoperatively the preemptive group showed lower scores (median difference -1.0 [95% CI -1.0 to 0.0], P = 0.040). Opioid use at other time points, QoR-15K scores, and laboratory tests showed no significant differences between the groups. Postoperative opioid consumption was not significantly different between preemptive and preventive administration of acetaminophen/ibuprofen in patients undergoing RALP.
This systematic review and meta-analysis analyzed the utility of the Analgesia Nociception Index (ANI) in detecting intraoperative and procedural pain in sedated patients. A comprehensive search of the Cochrane Central Register of Controlled Trials, Ovid-MEDLINE, Ovid-Embase, and Google Scholar databases was performed to identify relevant studies. The primary outcome was the diagnostic accuracy of ANI, assessed by pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR). Secondary outcomes were the correlation between ANI and pain assessment scales, the effect of norepinephrine (NE) on ANI, and differences in opioid consumption between the ANI-guided and control groups. Eleven studies were included in the systematic review, with ten studies incorporated into the meta-analysis. ANI demonstrated moderate sensitivity (0.746, 95% confidence interval [CI] = 0.683-0.803) and specificity (0.776, 95% CI = 0.741-0.808) for detecting intraoperative and procedural pain, with a pooled DOR of 10.491. ANI was lower in the pain state than that in the no-pain state (standardized mean difference [SMD] = -1.140, 95% CI = -1.239 to -1.041, I2 = 93.63%). ANI-guided analgesia was associated with a significant reduction in opioid consumption (SMD = -0.410, 95% CI = -0.643 to -0.178, I2 = 0.0%). There were no significant differences in ANI between the NE and control groups. ANI showed a negative correlation with pain scales (r = -0.110 to -0.470). ANI effectively differentiated between the pain and non-pain states in sedated patients with moderate diagnostic accuracy and helped reduce opioid consumption. However, the high heterogeneity suggests the need for cautious interpretation.
The spinal nerve ligation (SNL) model induces neuropathic pain through peripheral nerve injury, leading to central sensitization and neuroinflammation. Recent evidence suggests that activation of Mincle (macrophage-inducible C-type lectin) in the spinal cord may also trigger pain hypersensitivity without peripheral nerve injury. This study compared the effects of SNL and spinal Mincle activation on pain behavior and neuroglial activation. Pain hypersensitivity was evaluated following a single intrathecal (i.t.) injection of the Mincle ligand, trehalose-6,6'-dibehenate (TDB) at doses of 0.1 μg, 1 μg, or 10 μg (single injection, S-TDB). In a separate group, rats received repeated i.t. TDB injection (10 μg/day for 2 days, R-TDB) or surgery for SNL. Pain behaviors were assessed for 28 days. Spinal expression of microglia (Iba1) and astrocytes (GFAP) was analyzed via immunofluorescence in R-TDB and SNL groups. I.t. TDB administration at all tested doses produced significant pain hypersensitivity from day 1 to day 28, with no clear dose-dependent effects. Repeated i.t. TDB administration led to greater mechanical allodynia than S-TDB, but thermal responses were similar. Compared to SNL, the R-TDB group produced a comparable pain hypersensitivity to SNL but exhibited faster activation of microglia and astrocytes. Spinal Mincle receptor activation via i.t. TDB induces persistent pain hypersensitivity in the absence of peripheral nerve injury, accompanied by a more rapid neuroinflammatory response than that observed in the SNL model. These findings support Mincle activation as a potential experimental model for neuroinflammationassociated neuropathic pain.
Neuropathic pain remains a major challenge in pain management because of its complex mechanisms and suboptimal response to conventional treatments, which often provide incomplete relief and carry the risk of adverse effects. Injections of 5% glucose in water (D5W) delivered via intradermal, subcutaneous, fascial, or perineural glucopuncture have emerged as a minimally invasive and safe therapeutic option. Although the exact mechanism has not been fully elucidated, the proposed pathways include transient receptor potential vanilloid 1 modulation, suppression of neurogenic inflammation, and stabilization of C-fiber excitability. Clinical studies, ranging from case reports to randomized controlled trials, have suggested the efficacy of this approach in postherpetic neuralgia, entrapment neuropathies, chronic tendinopathies, and fascial pain, with minimal complications. Unlike prolotherapy, glucopuncture uses isotonic glucose (D5W), and primarily exerts neuromodulatory rather than regenerative effects. Current evidence, while limited, indicates meaningful and sustained pain relief in selected neuropathic conditions with a favorable safety profile and low procedural complexity. This review outlines key mechanisms, clinical outcomes, differences between related interventions, and clinical considerations.
Alpha-tocopherol (vitamin E) is a fat-soluble antioxidant with neuroprotective properties. There is a gap in research regarding the anti-nociceptive and anti-inflammatory effects of alpha-tocopherol in different tests of nociception as well as its signaling pathways. Therefore, this study aimed to assess the anti-nociceptive and anti-inflammatory effects of alpha-tocopherol in vivo and examine the potential involvement of transient receptor potential vanilloid 1 (TRPV1) and downstream kinase pathways, particularly protein kinases protein kinase A (PKA) and protein kinase C (PKC). Male Swiss albino mice were used in acetic acid-induced writhing, immersion tail-flick, and hot-plate tests for nociception while male Wistar rats were used in carrageenan-induced paw edema assay for inflammation. Alpha-tocopherol (50 mg/kg, i.p.), alone or in combination with TRPV1 antagonist (capsazepine) or PKC/PKA inhibitors (Go 6976, H89, respectively) was administered, followed by conducting the behavioral tests. TRPV1 expression in brain and skin tissues was examined using immunohistochemistry. Alpha-tocopherol significantly reduced writhing responses and extended heat latency in thermal tests. The TRPV1 was involved in the hot-plate and immersion tail-flick assays, while PKC and PKA pathways were implicated in the supraspinal analgesic effect (the hot plate test). Alpha-tocopherol (20 μg) did not exert any significant anti-inflammatory effect in the carrageenan model. Intense TRPV1 immunolabeling was observed in the alpha-tocopherol/ carrageenan condition, particularly in the skin. Alpha-tocopherol possesses a strong anti-nociceptive effect through TRPV1 modulation via PKC/PKAdependent mechanisms. These findings suggest that alpha-tocopherol can be used as an adjuvant in multimodal pain management protocols.
Elderly patients with herpes zoster ophthalmicus (HZO) have a high risk to progress to postherpetic neuralgia (PHN). Thus, early implementation of optimal treatment could lower the prevalence of PHN. We collected 50 elderly acute HZO patients treated with short-term peripheral nerve stimulation (PNS) or supraorbital nerve pulsed radiofrequency (PRF) from three hospitals from October 2022 to October 2023. All patients completed 12-month follow-up. The Visual Analog Scale (VAS), Barrow Neurological Institute (BNI) score and Pittsburgh Sleep Quality Index (PSQI) were used to assess the pain intensity and sleep quality. The pain intensity and sleep quality of all patients was significantly relieved after surgery. Following surgery, the PNS group's VAS and PSQI scores were statistically lower than those of the PRF group, and they also took less medication. At 3 months after surgery, the incidence of clinically significant PHN in the PNS group was lower than the PNS group. At 12 months after surgery, the BNI scores of the PNS group were better than the PRF group. Early application of short-term PNS or PRF for acute-phase HZO in the elderly can relieve pain. Compared to PRF, PNS may offer superior pain management, enhance quality of life, and contribute to a downward trend in the incidence of PHN.
Manipulation therapy (MT) relieves pain in nervous system disorders by reducing inflammation. Although evidence suggests MT is beneficial for neuropathic pain (NP), its molecular mechanisms remain unclear. This study investigated whether MT could reverse NP-related epigenetic changes and elucidated the potential mechanisms of NP. An NP model was established via spinal nerve ligation (SNL), and MT was administered at acupoints Jumping Round (GB30), Yang Mound Spring (GB34), and Suspended Bell (GB39) for 14 days. Mechanical and thermal pain in rats were evaluated using the mechanical paw withdrawal threshold and thermal paw withdrawal latency tests. Inflammatory cytokine levels in spinal cord neurons were quantified using enzyme-linked immunosorbent assay. Total N6-methyladenosine (m6A) levels were assessed by colorimetric analysis, while target genes were validated using methylated RNA immunoprecipitation succeeded by quantitative polymerase chain reaction, immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction. The outcomes indicated that MT significantly attenuated SNL-induced pain hypersensitivity. The therapeutic effects of MT were correlated with global m6A methylation in spinal cord neurons. Moreover, MT affected the toll-like receptor 4 (TLR4) signaling pathway's expression by modulating suppressor of cytokine signaling 1 protein (SOCS1) mRNA m6A methylation levels, consequently reducing the secretion of neuroinflammatory cytokines interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α), thereby alleviating NP. This study provides evidence that MT effectively ameliorates NP by modulating inflammation and RNA m6A methylation in the spinal cord via the SOCS1/TLR4 pathway.
This study evaluated and compared invalidation domains (discounting and lack of understanding) in patients with fibromyalgia (FM) and non-FM chronic musculoskeletal pain. The relationship between invalidation and depression was also investigated to clarify the role of FM. A total of 207 patients (145 FM and 62 non-FM) completed questionnaires including the Illness Invalidation Inventory (3*I), Widespread Pain Index (WPI), Revised Fibromyalgia Impact Questionnaire (FIQR), and Beck Depression Inventory-second edition (BDI-II). Adjusted linear regression analyses were performed to assess the association between the 3*I and BDI-II, and univariate and multivariate logistic regression analyses were used to examine the relationships between FM (as the dependent variable) and other variables. WPI, FIQR, BDI-II, and 3*I scores were significantly higher in FM patients than in non-FM patients. The BDI-II total score was found to be a significant predictor of discounting and lack of understanding stemming from spouse and family sources in both groups, with slightly stronger effects in the non-FM group than in FM patients. In multivariate regression analysis, discounting from family sources (odds ratio [OR] = 1.81, 95% confidence interval [CI] = 1.02-3.20, P = 0.040) and the BDI-II total score (OR = 1.12, 95% CI = 1.06-1.20, P = 0.001) remained a determinant of having FM. The higher frequency of invalidation in FM patients is not fully explained by depression because of weaker statistical relationships between invalidation and depression in FM rather than other pain disorders.
Cognitive function is negatively affected in different chronic painful conditions. This study aimed to examine the relationship between pain intensity, menstrual symptoms, catastrophization, and cognitive functions in young women with primary dysmenorrhea. This cross-sectional study comprised 132 nulliparous young women with primary dysmenorrhea. Sociodemographic characteristics and detailed medical, obstetric, and urogynecological history were recorded. Menstrual pain intensity was evaluated with the Visual Analogue Scale, symptoms experienced during the menstrual cycle with the Menstruation Symptom Questionnaire (MSQ), pain-related emotions with the Pain Catastrophizing Scale (PCS), and cognitive functions with the Montreal Cognitive Assessment (MoCA) and Stroop test. All evaluations were performed in the periovulatory phase. The mean MoCA total score was 24.31 ± 4.86 in young women with primary dysmenorrhea. The MoCA visuospatial/executive subscale showed negative correlations with menstrual pain intensity, pain duration, complaint duration, MSQ coping strategies, PCS rumination, PCS helplessness, and PCS total scores (r = -0.191 to -0.291, P < 0.05). In addition, Stroop 4-time showed a weak positive correlation with complaint duration (r = 0.236, P = 0.016) and PCS rumination scores (r = 0.222, P = 0.024). Young women with primary dysmenorrhea had low MoCA scores. In primary dysmenorrhea, visuospatial/executive cognitive function and selective attention were impaired, especially in relation to the severity of menstrual pain, pain duration, some menstrual symptoms, and pain catastrophization. Cognitive training, especially to improve visuospatial/executive cognitive function and selective attention, should be included in pain management programs applied to women with primary dysmenorrhea.
Trigeminal neuralgia (TN) severely reduces quality of life and frequently recurs. Managing recurrent TN is challenging. Although radiofrequency thermocoagulation (RFT) and percutaneous balloon compression (PBC) are standard minimally invasive options, direct comparative evidence for their efficacy in recurrent TN is limited. The aim of this study was to evaluate the efficacy and safety of RFT versus PBC for RFT recurrent TN. A retrospective analysis of 174 patients with recurrent TN who had previously undergone RFT and required secondary intervention (RFT group, n = 99 or PBC group, n = 75) between January 1, 2020 and April 30, 2024. The Numeric Rating Scale score, recurrence-free survival rate, Barrow Neurological Institute facial numbness (BNI-N) score, and other complications were assessed before surgery and all postoperative follow-up time points. All patients achieved complete pain relief immediately following the procedure in both groups (P < 0.05). Kaplan-Meier survival analysis showed significantly longer recurrence-free survival in the PBC group than in the RFT group (P < 0.0001). Comparative analysis revealed lower BNI-N scores in the RFT group at all assessment time points (P < 0.001). No severe complications were observed in either of the 2 groups. Both repeat RFT and PBC can effectively provide short-term pain relief for patients with RFT recurrent TN. Compared to repeat RFT, PBC represents a preferable therapeutic option for long-term pain relief efficacy and lower recurrence rates at 1-year follow-up.