Pain and Therapy最新文献

Introduction: Tension-type headache (TTH) is the most prevalent primary headache disorder worldwide, yet its neurobiological underpinnings remain partially understood. Neurotransmitter and neuropeptide alterations have been proposed as contributing factors, but evidence remains inconsistent. This systematic review aims to synthesize the available evidence on peripheral and central neurotransmitter alterations in patients with TTH, and to identify potential neurochemical targets for future investigation.

Methods: We searched PubMed and Embase (Ovid) for studies reporting levels of neurotransmitters or neuropeptides in human samples from individuals with TTH. A total of 30 studies were included. Data on study design, sample type, and measured neuromodulators were extracted and narratively synthesized.

Results: No single neurotransmitter or neuropeptide emerged as a consistent biomarker or central mediator of TTH. However, some systems showed recurring alterations. Substance P levels were elevated in both salivary and platelet samples. Findings on endogenous opioids were mixed, with β-endorphins often reduced and methionine-enkephalin (MET) elevated, possibly reflecting compensatory responses. Serotonin data were heterogeneous and inconclusive, whereas nitric oxide may play a role in headache induction, independent of calcitonin gene-related peptide (CGRP).

Conclusions: Despite variability in results, substance P, endogenous opioids, and nitric oxide emerged as the most promising targets for further studies. Future research should prioritize standardized methodologies to clarify the role of these pathways in TTH pathophysiology.

With 80% of migraines diagnosed and managed by primary care clinicians, a knowledge of standard of care and novel therapy is essential for those caring for people with this chronic disease. This review describes a new class of medication, calcitonin gene-related protein (CGRP) antagonists, known as gepants and their use with the focus on the general class of gepants rather than any specific type. These medications were developed specifically for acute and preventive treatment of migraine and appear to be more tolerable with fewer side effects than standard-of-care medications. Previous standard-of-care medications were developed for managing non-migraine disorders but were found to demonstrate efficacy in migraine control despite not directly targeting migraine pathophysiology. Evidence-informed review of the literature and real-world application of gepants is presented to provide a solid understanding of the class and guidance for use.

Introduction: This study aims to evaluate the efficacy and safety of Crisugabalin in patients with diabetic peripheral neuropathic pain (DPNP), with a focus on its rapid onset of action.

Methods: All the analyses in this study were based on data from a phase 2/3 adaptive randomized clinical trial that enrolled 596 patients. Participants were categorized into four treatment groups according to the intervention received: Crisugabalin 40 mg/day, Crisugabalin 80 mg/day, placebo, and Pregabalin 300 mg/day. The primary endpoint was the change in the average daily pain score (ADPS) over a 13-week treatment period. Secondary endpoints included changes in the Numeric Rating Scale (NRS) and the daily sleep interference score (DSIS) during the first two weeks of treatment.

Results: Both Crisugabalin treatment groups (40 mg/day and 80 mg/day) demonstrated statistically significant reductions in ADPS compared to the placebo group starting from week 1 and continuing through week 13 (P < 0.05). Significant differences in pain relief for the Pregabalin group were observed only from week 6. Improvements in NRS and DSIS scores were also noted in both Crisugabalin groups, with statistically significant enhancements evident as early as day 2 of administration. Safety assessments indicated that Crisugabalin was well-tolerated, with a low incidence of serious adverse events and no significant increase in dropout rates among participants.

Conclusion: The findings suggest that Crisugabalin offers effective pain relief with an acceptable safety profile, highlighting its rapid onset in patients with DPNP.

Clinical trial registration: Clinical trial registration number derived from our parent project, we have retained the original registration identifier: NCT04647773.

Introduction: Therapy habituation is a barrier to sustained success with spinal cord stimulation (SCS). Fast-acting subperception therapy (FAST) is a low-frequency, subperception waveform that can achieve rapid wash-in pain relief via the surround inhibition mechanism. FAST-Autodose is an automated neural dosing schedule designed to provide effective pain relief while potentially reducing habituation and maintaining therapy within an efficient therapeutic window-thus eliminating the need for manual patient adjustments. We assessed the efficacy of FAST-Autodose and provide preliminary long-term outcomes.

Methods: We conducted a retrospective review of consecutive patients from a multicenter, observational study in the USA who had received SCS and used FAST-Autodose to manage their chronic pain of the low back and/or lower limbs. The numerical rating scale (NRS) evaluated the overall pain intensity until the last follow-up postimplantation.

Results: Data were collected from 73 patients who had used FAST-Autodose for 11.9 ± 6.8 months on average. At the last follow-up visit (average 1.8 ± 1.5 years after implantation), the NRS score for overall pain decreased by 5.1 ± 2.8 points, to a mean of 2.1 ± 2.0 (p < 0.0001) and 69% of patients reported minimal pain (NRS ≤ 2/10). In total, 23 patients had been implanted for more than 3.5 years and had used FAST-Autodose for a mean of 17.7 ± 5.9 months; in these patients, the mean NRS pain score decreased by 6.1 ± 2.0 points to 1.6 ± 1.2 points (p < 0.0001).

Conclusions: FAST-Autodose is a novel, automated, subperception paradigm for SCS. In our study, this program delivered significant and sustained pain relief in patients with chronic low back and/or leg pain who had been implanted with SCS for up to 3.6 years. These preliminary results constitute a promising rationale for larger, prospective studies on the long-term efficacy of FAST-Autodose.

Clinical trial registration: Trial registered at clinicaltrials.gov (ID: NCT01550575).

Introduction: Shoulder pain can be a chronic, disabling condition resulting in major procedures like surgery that are invasive, costly, and pose significant risks to patients. Minimally invasive interventions that provide durable relief can improve outcomes while enabling patients to avoid accruing additional healthcare costs. The present survey study evaluated durability of pain relief in a real-world shoulder pain population following percutaneous 60-day peripheral nerve stimulation (PNS) treatment.

Methods: A cross-sectional follow-up survey assessed follow-up outcomes among patients who received 60-day PNS for chronic shoulder pain. Outcomes included patient-reported percent pain relief, average and worst pain scores, and patient impression of change in quality of life, physical function, and sleep. Patients also reported other treatments and interventions used for their shoulder pain since the 60-day PNS treatment including changes in medication usage.

Results: Among 489 survey participants (mean follow-up 21 months, range 6-60), 83% (405/489) reported no subsequent radiofrequency ablation, permanent implant, or surgery following 60-day PNS. Within this subset, 87% reported ongoing improvement in at least one domain at follow-up, including 71% who maintained ≥ 50% pain relief, and more than half who reported much or very much improved quality of life (61%), physical function (57%), or sleep (57%). Among those using PNS seeking to avoid surgery (n = 265), 81% reported no subsequent surgery, with 77% of those patients maintaining ≥ 50% pain relief. Outcomes were consistent across follow-up durations and shoulder pain etiologies.

Conclusions: This real-world evidence demonstrates that a large majority of responders to 60-day PNS may experience durable shoulder pain relief and other improvements, with benefits demonstrated up to 5 years post treatment. The low rate of progression to subsequent interventions including surgery suggests potential for healthcare economic benefit, supporting 60-day PNS as both a clinically effective and potentially economically advantageous approach for appropriate patients.

Cancer-related pain (CrP) is one of the most frequent and debilitating issues that affect the quality of life of patients with cancer. Systemic analgesics, particularly opioids, have been the cornerstone of pain management. However, the following shortcomings of the mentioned therapies, such as side effects, tolerance, and inadequate relief in refractory cases, make implementing a more complete, multimodal treatment plan necessary. Interventional pain management (IPM) uses specific invasive procedures, with different degree of invasiveness, such as nerve blocks, neurolysis, neuromodulation, and intrathecal drug delivery systems to provide effective pain relief with reduced adverse effects compared with opioids. These approaches are frequently underutilized due to delayed referrals, insufficient awareness, and logistic inefficiencies, which delay access to pain management centers specializing in care for patients in pain. Recent technological advancements offer the potential to overcome these barriers, including artificial intelligence-driven decision support systems and automated referral pathways, enabling early intervention and individualized pain treatment plans. The future of CrP management should shift from the current reactive model to a proactive approach, enabling the earlier incorporation of interventional techniques into treatment plans. The integration of interdisciplinary collaboration and technological innovations will enhance cancer pain management and progress from current outdated approaches to provide more effective and timely pain relief for patients with chronic refractory cancer pain.

Introduction: Peripheral neuropathic pain after nerve injury (PNI) caused by surgery or trauma can severely impact daily life. The high-concentration capsaicin patch (HCCP, 179 mg) is a topical therapy approved for peripheral neuropathic pain, including PNI. This study utilizes data from the German Pain e-Registry (GPeR) to investigate the real-world effectiveness of HCCP in managing PNI across multiple treatments over 1 year.

Methods: CASPAR is a retrospective, non-interventional cohort study investigating patients with peripheral neuropathic pain treated with HCCP. The present analysis included 499 patients with PNI who received ≥ 1 HCCP with ≥ 12 months of follow-up. Key measures included pain intensity, quality of life (QoL), affective distress, sleep disturbances, and overall functioning. Furthermore, analgesic use and adverse events associated with HCCP treatment were evaluated.

Results: The mean average daily pain intensity (API) decreased from 52.5 mm on the visual analog scale (VAS) at baseline to 21.5 mm at month 12 in patients receiving four HCCPs. At month 12, a ≥ 30% reduction in API was observed in 25.8%, 44.9%, 85.3%, and 97.8% of patients receiving one, two, three, and four HCCP treatments, respectively. Significant improvements were also noted in physical and mental QoL, sleep, mood, and daily functioning. Patients receiving three or four HCCP treatments maintained pain relief and symptom improvements over the 12-month period, whereas those who discontinued treatment after one or two treatments experienced symptom rebound. In addition, repeated HCCP treatments were associated with a marked reduction in concomitant analgesic use and an increase in days of normal activities. Adverse events were mild-to-moderate application-site reactions, consistent with the well-established safety profile of HCCP.

Conclusions: HCCP treatment is associated with reductions in pain intensity and improvements in sleep, mood, and overall QoL in patients with PNI. These benefits are amplified with continued treatment and are accompanied by reduced use of concomitant analgesics and more days of usual activities, although a direct causal relationship cannot be confirmed within the context of this observational study.

Clinical trial registration: EU PAS number: EUPAS1000000106.

Introduction: Breast cancer surgery is a common surgical procedure often associated with acute and chronic postoperative pain. As part of multimodal analgesia, the erector spinae plane block (ESPB) has been shown to effectively alleviate pain after breast cancer surgery. This study is the first to apply the posterior quadratus lumborum block (posterior QLB) for perioperative analgesia in breast cancer surgery. The aim of this research was to evaluate whether ESPB and QLB2 can relieve acute and chronic pain following breast cancer surgery.

Methods: A total of 120 female patients undergoing breast cancer surgery were randomly assigned to receive either ESPB, posterior QLB, or no intervention. All patients were administered sufentanil patient-controlled intravenous analgesia postoperatively. The primary outcome was the visual analog scale (VAS) pain scores recorded at 2, 6, 18, 24, and 48 h post-surgery under rest and motion conditions. Secondary outcomes included the incidence of moderate-to-severe pain within 24 and 48 h post-surgery, intraoperative fentanyl cumulative dosage, postoperative rescue analgesia, chronic pain incidence, recovery quality of life, and adverse events.

Results: Compared to the group receiving conventional treatment (group C), the incidence of moderate-to-severe pain within 24 h post-surgery was significantly lower in both the group receiving ESPB (group E; 16.7% vs. 46.2%, P < 0.05) and the group receiving QLB (group Q; 20.5% vs. 46.2%, P < 0.05). Additionally, the proportion of patients requiring rescue analgesia was significantly reduced in both group E and group Q, compared to group C (group C vs. E vs. Q: 30.8% vs. 7.1% vs. 10.3%, P = 0.007; group C vs Q: 30.8% vs. 10.3%, P = 0.025; group C vs. E: 30.8% vs 7.1%, P = 0.006; group Q vs. E: 10.3% vs. 7.1%, P = 0.141). At 3 months post-surgery, group Q had a significantly lower incidence of chronic pain compared to both group C (19.5% vs. 71.8%, P < 0.05) and group E (19.5% vs. 57.1%, P < 0.05). No significant differences were observed between the groups in terms of VAS scores at 2, 6, 18, 24, or 48 h, intraoperative fentanyl consumption, postoperative nausea and vomiting, time to first mobilization, time to first oral intake, the length of hospital stay, or Quality of Recovery-15 Items (QoR-15) scores at 3 months post-surgery (all P > 0.05).

Conclusion: Compared with conventional intravenous analgesia, the combination of ultrasound-guided ESPB and posterior QLB significantly reduces the incidence of moderate-to-severe pain and the need for rescue analgesia within 24 h post-surgery. Furthermore, a single posterior QLB significantly reduces the incidence of chronic pain at 3 months post-surgery in patients with breast cancer.

Trial registration: Clinical trial number: ChiCTR2000041471.

Introduction: The primary analysis of the MiroTAS study in patients with lumbar spinal stenosis (LSS) taking non-steroidal anti-inflammatory drugs showed that mirogabalin add-on therapy further improved pain and quality of life (QOL) without new safety concerns.

Methods: This post hoc analysis of the MiroTAS study examined the timing of onset of mirogabalin-related adverse drug reactions (mrADRs) (composite of somnolence, dizziness, edema, and peripheral edema), factors affecting safety and efficacy, and the relationships between baseline numbness severity (by spine painDETECT questionnaire [SPDQ] score), EQ-5D-5L scores, leg pain improvement (by visual analogue scale [VAS]), and patient satisfaction (by Patient Global Impression of Change [PGIC] scores).

Results: Among 110 patients, there were no significant differences in the incidence rates of mrADRs by patient characteristics. The mrADRs occurred mainly after the first administration and uptitration period of mirogabalin. EQ-5D-5L scores significantly improved from baseline to week 12 in patients with mrADRs vs those without (difference 0.0767; p = 0.0304 by t test). The proportion of patients with PGIC scores ≤ 3 at week 12 was numerically higher in patients with mrADRs vs those without. There were no differences in the percentage of patients with reduced leg pain by VAS score (improvement ≥ 20 mm) at week 12 by patient characteristics except for spondylolysis/spondylolisthesis as a complication. Baseline SPDQ numbness scores were positively correlated with improvement in EQ-5D-5L at week 12 (Spearman's rank correlation coefficient 0.2811, p = 0.0092).

Conclusions: Mirogabalin was not related to specific patient characteristics regarding the onset of mrADRs and was effective for LSS regardless of patient characteristics. Caution is needed regarding the onset of mrADRs after first administration and uptitration of mirogabalin, but these may not reduce QOL or patient satisfaction. Patients with high numbness scores may be more likely to benefit from treatment with mirogabalin in terms of QOL.

Trial registration: Japan Registry of Clinical Trials (jRCTs021200007).