Pain and Therapy最新文献

Introduction: This study aimed to assess economic burden and treatment characteristics of patients with chronic low-back pain (cLBP) transitioning from oral Schedule II (CII) short-acting opioids (SAO) to oral CII long-acting opioids (LAO) or Belbuca^® (buprenorphine buccal film, BBF).

Methods: Merative MarketScan^® commercial US claims (2019-2023) were retrospectively analyzed. Index date was the first BBF or LAO prescription date. The observation covered 6-month pre-index and 12-month follow-up periods. Patients were adults with ≥ 2 low-back pain and ≥ 1 SAO prescription pre-index claims. Cases with BBF-LAO switching, coverage gap, or cancer/HIV were excluded. Economic burden and treatment characteristics were explored during follow-up. Rescue medication utilization trends were also analyzed (6-month pre-index vs. 6-month follow-up). Propensity-score matching minimized the impact of patient characteristics.

Results: Study sample had 964 patients per cohort. Despite higher prescription costs in BBF ($10,417 vs. $8238, p = 0.007), total and cLBP-related costs were similar. BBF had fewer outpatient visits (33.1 vs. 35.4, p = 0.038), hospitalizations (0.2 vs. 0.3, p = 0.041), cLBP-related hospitalizations (0.04 vs. 0.08, p = 0.013), and shorter cLBP-related hospital stay (0.14 vs. 0.33 days, p = 0.023). BBF also had fewer patients with ED visits (36.9% vs. 41.6%, p = 0.036) and cLBP-related hospitalizations (3.5% vs. 6.1%, p = 0.008). Adherence and treatment duration between cohorts were similar, with fewer prescriptions in BBF (5.8 vs. 6.5, p = 0.003). Trends showed BBF had greater decreases in SAO treatment duration (- 15.4 vs. - 2.2 days, p < 0.001), prescription counts (- 0.9 vs. - 0.3, p < 0.001), and daily morphine milligram equivalents (- 9.7 vs. - 6.1, p = 0.015). However, more BBF-treated patients had buprenorphine patches (8.2% vs. 3.3%, p < 0.001) with more patch prescriptions (0.3 vs. 0.1, p < 0.001) and longer treatment duration (8.9 vs. 2.6 days, p < 0.001).

Conclusion: Study findings demonstrated similar healthcare expenditures between patients with cLBP transitioning from SAO to BBF and to LAO. Yet, initiating BBF may have lowered healthcare resource utilization and decreased further SAO utilization.

Introduction: Intrathecal drug delivery systems (IDDS) represent an advanced option for refractory craniofacial cancer pain, though optimal catheter tip positioning remains debated between anterior cisterna (AC) and high cervical (HC) approaches.

Methods: This multicenter retrospective cohort analyzed 108 patients with severe craniofacial cancer pain undergoing IDDS catheterization (33 AC; 75 HC) between January 2018 and December 2024. Propensity score matching (1:2 ratio) created balanced cohorts (33 AC versus 66 HC). Primary outcome was pain reduction (numerical rating scale), with minimum clinically important difference defined as ≥ 1.5-point reduction. Secondary outcomes included opioid requirements, intrathecal morphine dosing, conversion ratios, and safety.

Results: After matching, both approaches demonstrated comparable pain reduction, with 90.9% of AC and 92.4% of HC patients achieving minimum clinically important difference at 3 months (risk difference: 1.5%, 95% confidence interval [CI] -9.8 to 12.8%). HC patients required higher intrathecal morphine doses during the first 2 weeks (week 1: 285 versus 220 mcg/day; ratio: 0.77, 95% CI 0.65-0.91), with significantly different oral-to-intrathecal conversion ratios (week 1: 886 versus 667; ratio: 1.33, 95% CI 1.12-1.58); these differences resolved by 1 month. Complete systemic opioid discontinuation at 3 months was comparable between groups (63.6% AC versus 59.1% HC). Safety profiles differed, with AC patients experiencing more procedure-related complications (postdural puncture headache: 18.2% versus 4.5%), while HC patients showed trends toward more opioid-related adverse events.

Conclusions: Both AC and HC catheterization provide comparable pain control for refractory craniofacial cancer pain. The AC approach offers superior initial delivery efficiency but requires advanced technical skill, while the HC approach provides comparable long-term outcomes with a more familiar technique. Selection should be guided by institutional expertise and patient-specific risk profiles.

Addressing pain effectively remains a major global challenge for healthcare systems and public health initiatives. While this issue is pervasive worldwide, it is particularly pressing in the United States, where pain management using opioid analgesics has led to significant concerns due to widespread misuse, drug dependence, and overdose fatalities. A central dilemma for clinicians in pain management lies in balancing the delivery of sufficient pain relief while minimizing potential risks. Although preferential μ-opioid receptor (MOP) agonists, such as morphine and oxycodone, often remain a necessary therapeutic choice, particularly for individuals experiencing moderate to severe pain, their safety profiles present a clinical dilemma, as there are limited other options available to clinicians. A promising area of research focus is on the development of dual NOP/MOP receptor (NMR) agonists , compounds that co-activate the nociceptin/orphanin FQ (NOP) receptor and the MOP receptor. Despite sharing some structural homology with opioid receptors, the NOP receptor exhibits a distinct pharmacological profile. Activating the NOP receptor induces pain relief and, more importantly, counteracts important adverse effects associated with MOP activation including reduction in euphoria by inhibiting opioid-induced activation of dopaminergic neuron activity in the ventral tegmental area (VTA), which in turn reduces the likelihood of misuse. Preclinical data have shown a potential role of NOP activation in reducing the occurrence of opioid withdrawal symptoms and, perhaps most importantly, respiratory depression. Investigations in nonhuman primates support the NOP receptor's modulatory role, demonstrating that NOP agonism not only produced analgesia across various pain models (nociceptive, neuropathic, and inflammatory) but also lessened MOP-related negative outcomes, such as opioid reward-seeking behavior, the development of tolerance, and withdrawal symptoms. Preclinical studies using dual NMR agonists showed that administration of a NOP antagonist increased the side effects similar to those caused by a preferential MOP agonist, underscoring the role of NOP receptor activation in counteracting these adverse events. Altogether these findings suggest that dual NMR (NOP/MOP receptor) agonists represent a promising novel class of medications with the potential to achieve strong analgesia while lessening the side effects of opioid agonists.

Introduction: Chronic pelvic pain syndrome (CPPS) in women is a debilitating condition with a high prevalence (5-25%), yet its etiology remains unclear. This prospective observational study aimed to identify clinical and medical history covariates associated with CPPS to elucidate potential pathophysiological mechanisms.

Methods: A total of 225 women were evaluated in a gynecological pain clinic in Germany, including 41 patients with CPPS (≥ 6 months of lower abdominal pain) and 184 control patients undergoing routine gynecological screening. Exclusion criteria included pregnancy, pelvic malignancy, acute pelvic inflammation, and abnormal uterine bleeding. Covariates were assessed through structured clinical history and physical examination.

Results: Significant associations with CPPS were observed for prior pelvic surgery (72% vs. 45%, p = 0.003), bowel constipation (37% vs. 11%, p = 0.002), history of endometriosis (33% vs. 10%, p = 0.043), and prior trauma (27% vs. 11%, p = 0.013). In contrast, there were no significant differences in rates of depression (p = 0.376), use of psychopharmaceuticals (p = 0.757), pelvic floor abnormalities (p = 0.503), uterine retroversion (p = 0.330), or pelvic congestion (p = 0.455). Dysmenorrhea (59% vs. 42%) and vulvar pain (31% vs. 8%) were more frequent in the CPPS group, though not statistically significant. No differences were found in delivery mode, use of intrauterine devices, analgesics, hormonal replacement therapy, and other medications, or comorbidities such as diabetes, thyroid disease, hypertension, other pain diseases, or musculoskeletal disorders.

Conclusions: CPPS was not associated with several commonly suspected cofactors, including psychosomatic factors, pelvic congestion, or pelvic floor dysfunction. The findings suggest the existence of two subgroups of CPPS, the endometriosis-associated type and the neurovegetative type, associated with prior pelvic surgery, constipation, and trauma. This concept allows for the development of new targeted therapeutic strategies to successfully treat CPPS.

Migraine is one of the most common nervous system diseases in the world, which is characterized by recurrent severe headache, accompanied by gut microbiota imbalance and gut-brain axis dysfunction, seriously affecting the quality of life of patients. The existing treatment methods have some limitations, such as low diagnostic rate and drug dependence, so we should pay attention to the potential value of acupuncture, a traditional Chinese medicine therapy. This paper systematically reviews the mechanisms underlying the association between gut microbiota and migraine, and the pathways by which acupuncture intervention in migraine regulates gut microbiota. Studies have shown that patients with migraine generally have the phenomenon that the diversity of gut microbiota decreases, the abundance of beneficial bacteria decreases, and the proportion of harmful bacteria increases. The imbalance of gut microbiota promotes the disorder of intestinal metabolites, the destruction of the intestinal barrier and blood-brain barrier, the activation of trigeminal neurovascular system and central inflammation, and induces or aggravates migraine. Studies have found that acupuncture can regulate the diversity of gut microbiota and the abundance of beneficial bacteria through multiple targets, reduce the production of harmful metabolites, and protect the integrity of the intestinal barrier and blood-brain barrier. Acupuncture can relieve stress and negative emotion, and reduce the inducement of migraine. This review provides a theoretical basis for clarifying the mechanism of "microbiota-gut-brain axis (MGBA)" in acupuncture treatment of migraine, and also provides a new idea for the clinical standardized treatment of migraine.

Introduction: Endoscopic decompression is a favorable option for the treatment of spinal diseases. However, there have been few reports of unilateral biportal endoscopy-assisted unilateral laminotomy for bilateral decompression (UBE-ULBD) for the treatment of severe thoracic spinal stenosis (TSS) and ossification of ligamentum flavum (OLF) with a high ossification occupancy ratio. The purpose was to evaluate the safety and efficacy of UBE-ULBD for the treatment of severe TSS-OLF with an occupancy ratio > 60%.

Methods: The retrospective cohort study enrolled 40 patients with TSS-OLF from January 2021 to August 2023. All the patients presented with typical neurological symptoms with radiological one- or two-level thoracic OLF, receiving UBE-ULBD surgery with at least 2 years of follow-up. Preoperative and postoperative clinical and radiological data were reviewed and analyzed. In addition, operative time, postoperative drainage, postoperative length of stay, and complications were also recorded.

Results: There were 33 cases of TSS-OLF with a single level and 7 two-level cases included in the study. The UBE-ULBD surgery was successfully performed for all the patients with an average operative time of 111.6 min/level. The mean follow-up time was 33.5 ± 6.4 months. The modified Japanese Orthopaedic Association (mJOA) score (9.1 ± 0.8 vs. 5.3 ± 1.0) and Oswestry Disability Index (ODI) (31.8 ± 5.2 vs. 46.4 ± 3.3) were significantly improved at last follow-up compared to the preoperative score. The mean recovery rate (RR) was 65.0%, with an effective rate of 100%. The mean preoperative ossification occupancy ratio was 76.7% and the ossification was removed for all cases with adequate decompression and radiological outcomes. The mean dural sac cross-sectional area (DSCA) expansion rate in magnetic resonance imaging (MRI) was 228.4 ± 115.8%.

Conclusions: UBE-ULBD is a technically demanding and feasible, efficient, and minimally invasive option for the treatment of severe one- or two-level OLF-TSS with a high ossification occupancy ratio > 60% with excellent clinical and radiological outcomes.

Primary trigeminal neuralgia (TN) involving the V2 maxillary nerve presents unique therapeutic challenges. Traditional radiofrequency techniques at the semilunar ganglion often lack selectivity and carry risks of injuring adjacent nerves. The recently refined CT-guided foramen ovale puncture radiofrequency thermocoagulation technique has significantly improved outcomes for V2 TN. This narrative review systematically explores the evolution of radiofrequency treatment for V2 TN, with a particular focus on comparing the efficacy and safety of different puncture pathways. We emphasize the superior clinical utility of the infrazygomatic approach, which offers greater precision and fewer complications than the obsolete orbital and mandibular routes. Furthermore, we discuss the impact of technical innovations, such as personalized needle modification, on treatment precision. This review aims to consolidate current evidence and provide practical, evidence-based guidance for clinicians managing this complex pain condition.

Introduction: Pulsed radiofrequency (PRF) is a well-established neuromodulation technique widely used for managing neuropathic pain. Lumbosacral radicular pain, a common neuropathic condition, is often refractory to conventional treatments. Although dorsal root ganglion (DRG) PRF has emerged as a promising intervention, its therapeutic efficacy is often limited and variable, likely due to an incomplete understanding of its mechanisms. To elucidate the neural mechanisms underlying DRG PRF analgesia, this study characterized treatment-induced alterations in microstate spatiotemporal dynamics and examined their correlation with pain intensity, thereby assessing their potential as neurophysiological markers.

Methods: We recorded high-density electroencephalograms (EEG) in healthy controls and patients before and after DRG PRF treatment. Topographic differences were assessed using topographic analysis of variance (TANOVA). Microstate temporal parameters (duration, occurrence, coverage) and transition probabilities were analyzed. Pearson correlation analysis was performed between transition probabilities and visual analogue scale (VAS) scores.

Results: TANOVA revealed significant differences in microstate topographies among the three groups (p = 0.033), primarily attributed to microstates C and E. Although we found no significant differences in global temporal parameters or transition probabilities, our exploratory analysis revealed a reduction in the transition probability from microstate D to E (Delta TM D to E) in patients before DRG PRF treatment compared to healthy controls (p = 0.016, uncorrected). Notably, this reduction showed a trend toward normalization after treatment. Furthermore, we observed a significant negative correlation between Delta TM D to E and VAS scores (r = -0.459, p = 0.008).

Conclusion: DRG PRF alleviates neuropathic pain by normalizing interactions between large-scale brain networks, as evidenced by topographic reorganizations and trends toward normalized transition dynamics. The sensitivity of microstate metrics to these changes supports their potential as neurophysiological markers for assessing both pain-related brain dysfunction and treatment response.

Trial registration: The trial was registered on ClinicalTrials.gov with the following number: ChiCTR2500104921.

Introduction: This study investigates the prevalence of sleep disorders among patients with fibromyalgia syndrome (FMS) in French pain clinics, addressing a gap between international and national data. It also aims to describe associated factors such as quality of life (QoL), pain, daily functioning, and psychological symptoms.

Methods: The study included 508 patients with an average age of 46 ± 10 years. Patients attending a specialized chronic pain center, either at their initial consultation or within the first year of follow-up, completed online self-administered questionnaires. Questionnaire were related to sleep disorders, pain, anxiety and QoL.

Results: In this sample, sleep disorders were highly prevalent among French patients with FMS (95.3% with Pittsburgh Sleep Quality Index (PSQI) > 5; 69.9% with PSQI > 10). More than 13% were identified as being at high risk for sleep apnea, and 60% reported symptoms suggestive of restless leg syndrome (RLS). The median scores on the Brief Pain Inventory were 6.0 (Q1: 5.3-Q3: 7.0) for pain severity and 5.9 (Q1: 4.7-Q3: 7.1) for pain interference. The Hospital Anxiety and Depression Scale revealed a median anxiety score of 11.0 (Q1: 9.0-Q3: 15.0). Regarding the impact of FMS on daily life, the median score on the Fibromyalgia Impact Questionnaire was 59.0 (Q1: 44.0-Q3: 71.0).

Conclusions: In contrast to French estimates, this study revealed a high prevalence of sleep disorders among patients with FMS, underscoring a gap in care. A substantial proportion of patients were at high risk for RLS and a clinically relevant risk for sleep apnea. Anxiety, depression, and reduced QoL were also highly prevalent, reflecting the complex and multifactorial burden of FMS. These findings highlight the need for a comprehensive, patient-centered approach that includes targeted management of sleep disturbances as a core component of fibromyalgia care.

Introduction: Dexketoprofen/tramadol is a fixed-dose multimodal combination analgesic that significantly controls multiple acute pain states, and may have an important clinical application in providing pain control adequate to prevent the transition from acute to chronic postsurgical and low back pain. A consensus is needed to quantify and define the actual burden of postsurgical pain (PSP) and low back pain (LBP), which can support efforts toward effective approaches to manage potential pain chronification.

Methods: This study utilized a modified Delphi approach. A Scientific Committee set forth 28 statements on six themes about the burden of acute PSP and LBP, their potential transition to chronic pain, their pathophysiology, therapeutic approaches to stop this transition, and the role of multimodal analgesia in this context, specifically a fixed-dose combination oral product of dexketoprofen/tramadol. An international panel of healthcare professionals from various regions and relevant medical specialties participated in a Delphi study and were surveyed for consensus on a 5-point Likert scale with consensus defined as > 70% concordance. A round of online voting lasting 3 months and using an online survey platform was permitted for each participant.

Results: A total of 100 experts completed the Delphi survey. All the 28 proposed statements reached consensus > 70% in the first round of voting. A fixed-dose combination product, specifically dexketoprofen/tramadol was recognized as a multimodal analgesic which could effectively relieve acute pain and act to prevent its transition to chronic pain. The high global burden of chronic PSP (CPSP) and chronic LBP (CLBP) was identified as well.

Conclusions: Healthcare professionals who deal with pain recognize the burden of acute pain, the risks of acute pain transitioning to chronic pain, and inspire to avert the transition by providing effective multimodal control of acute pain. The role of fixed-dose combination analgesics, in particular dexketoprofen/tramadol, was recognized by consensus as an efficacious and safe therapy option for these acute pain syndromes. A Video Abstract is available for this article. To view, please see the online version of the manuscript or follow the 'Digital Features' link. A Video Abstract for The Role of Dexketoprofen/Tramadol in Multimodal Therapy to Prevent Acute Postsurgical and Acute Low Back Pain from Developing into Chronic Pain: A Delphi Consensus Study (MP4 112565 KB).