Pain and Therapy最新文献

Postherpetic neuralgia (PHN) manifests as persistent chronic pain that emerges after a herpes zoster outbreak and greatly diminishes quality of life. Unfortunately, its treatment efficacy has remained elusive, with many therapeutic efforts yielding less than satisfactory results. The research to discern risk factors predicting the onset, trajectory, and prognosis of PHN has been extensive. However, these risk factors often present as nonspecific and diverse, indicating the need for more reliable, measurable, and objective detection methods. The exploration of potential biological markers, including hematological indices, pathological insights, and supportive tests, is increasing. This review highlights potential biomarkers that are instrumental for the diagnosis, management, and prognosis of PHN while also delving deeper into its genesis. Drawing from prior research, aspects such as immune responsiveness, neuronal injury, genetic makeup, cellular metabolism, and pain signal modulation have emerged as prospective biomarkers. The immune spectrum spans various cell subtypes, with an emphasis on T cells, interferons, interleukins, and other related cytokines. Studies on nerve injury are directed toward pain-related proteins and the density and health of epidermal nerve fibers. On the genetic and metabolic fronts, the focus lies in the detection of predisposition genes, atypical protein manifestations, and energy-processing dynamics, with a keen interest in vitamin metabolism. Tools such as functional magnetic resonance imaging, electromyography, and infrared imaging have come to the forefront in the pain signaling domain. This review compiles the evidence, potential clinical implications, and challenges associated with these promising biomarkers, paving the way for innovative strategies for predicting, diagnosing, and addressing PHN.

Introduction: The best treatment yielding clinical benefits was still equivocal and controversial for the treatment of recalcitrant plantar fasciitis (PF). This study aimed to propose a novel combination strategy of ultrasound-guided percutaneous radiofrequency ablation (RFA) and corticosteroid injection (CI) for recalcitrant PF, and to compare its therapeutic effects with CI alone and continued conservative management.

Methods: We retrospectively reviewed consecutive patients with recalcitrant PF who underwent combined strategy (RFA + CI), CI alone, and continue conservative treatment at our institution between October 2021 and February 2023. The technical pearls were described elaborately. A comparison of demographic data and clinical outcomes, including visual analog scale (VAS), Ankle-Hindfoot Scale (AOFAS-AHS), and plantar fascia thickness, were conducted among the three groups.

Results: Seventy-one eligible patients were enrolled in this study, with 17 in the combined strategy group, 25 in the CI group, and 29 in the continued conservative treatment group. Both the combined strategy group and the CI group showed significant improvements in VAS scores, AOFAS-AHS scores, and significant reductions in plantar fascia thickness during the 12-month follow-up period compared to those preoperatively (P < 0.05). The combined strategy group achieved comparable immediate pain relief to the CI group after the intervention ([25.7 ± 15.7] vs. [20.6 ± 17.6], P = 0.850). However, the combined strategy group demonstrated superior improvement in symptom and function compared to the CI group at the 3-month (VAS: [21.9 ± 13.5] vs. [39.6 ± 20.4]; AOFAS-AHS: [77.9 ± 12.4] vs. [60.5 ± 17.4], P < 0.05) and 12-month follow-up (VAS: [15.7 ± 12.0] vs. [56.8 ± 17.5]; AOFAS-AHS: [84.5 ± 10.7] vs. [53.8 ± 12.4], P < 0.05). Obvious adverse effects or complications were not identified in either group, while two cases (11.8%) in the combined strategy group and five cases (20.0%) in the CI group experienced unsatisfactory symptom remission.

Conclusions: We introduced and detailed a novel combination strategy involving ultrasound-guided percutaneous RFA and CI for treating recalcitrant PF. The strategy is both effective and safe in alleviating pain and enhancing function throughout the entire treatment course.

Introduction: Chronic pain is a public health issue, leading to substantial healthcare costs and diminished quality of life for sufferers. While the role of anxiety in pain modulation has been extensively studied, the effects of other emotional states on the body's pain control mechanisms remain less understood. This study sought to explore how different emotions (happiness, anger, sadness, and interest) affect conditioned pain modulation (CPM) and the wind-up phenomenon in healthy adults.

Methods: This randomized controlled, cross-over trial involved 28 healthy participants aged 18-60. Participants watched video clips designed to induce specific emotions: happiness, anger, sadness, and interest. Emotional states were assessed using a 7-point Likert scale. Pain modulation was measured using CPM and the wind-up phenomenon. CPM was assessed with a hot water bath as the conditioning stimulus and pressure pain tolerance as the test stimulus. Wind-up was measured using pinprick needle stimulators and a visual analog scale. Data were analyzed using paired t tests to compare pre- and post-emotion induction values.

Results: Significant changes in emotional self-assessment values were observed for all emotions. Happiness increased CPM (4.6 ± 11.4, p = 0.04277), while sadness - 9.9 ± 23.1, p = 0.03211) and anger - 9.1 ± 23.3, p = 0.04804) decreased it. Interest did not significantly alter CPM (- 5.1 ± 25.8, p = 0.31042). No significant effects were found for the wind-up phenomenon across any emotional states.

Conclusion: This study shows that emotional states significantly affect the body's ability to modulate pain. Positive emotions like happiness enhance pain inhibition, while negative emotions such as sadness and anger impair it. These findings suggest that emotional modulation techniques could be integrated into pain management strategies to improve patient outcomes. Further research should explore a broader range of emotions and include objective measures to validate these results.

Introduction: Drawbacks of fixed-output spinal cord stimulation (SCS) screening trials may lead to compromised trial outcomes and poor predictability of long-term success. Evoked compound action potential (ECAP) dose-controlled closed-loop (CL) SCS allows objective confirmation of therapeutic neural activation and pulse-to-pulse stimulation adjustment. We report on the immediate patient-reported and neurophysiologic treatment response post-physiologic CL-SCS and feasibility of early SCS trial responder prediction.

Methods: Patient-reported pain relief, functional improvement, and willingness to proceed to permanent implant were compared between the day of the trial procedure (Day 0) and end of trial (EOT) for 132 participants in the ECAP Study undergoing a trial stimulation period. ECAP-based neurophysiologic measurements from Day 0 and EOT were compared between responder groups.

Results: A high positive predictive value (PPV) was achieved with 98.4% (60/61) of patients successful on the Day 0 evaluation also responding at EOT. The false-positive rate (FPR) was 5.6% (1/18). ECAP-based neurophysiologic measures were not different between patients who passed all Day 0 success criteria ("Day 0 successes") and those who did not ("needed longer to evaluate the therapy"). However, at EOT, responders had higher therapeutic usage and dose levels compared to non-responders.

Conclusions: The high PPV and low FPR of the Day 0 evaluation provide confidence in predicting trial outcomes as early as the day of the procedure. Day 0 trials may be beneficial for reducing patient burden and complication rates associated with extended trials. ECAP dose-controlled CL-SCS therapy may provide objective data and rapid-onset pain relief to improve prognostic ability of SCS trials in predicting outcomes.

Trial registration: The ECAP Study is registered with ClinicalTrials.gov (NCT04319887).

Introduction: Cardiovascular (CV) risk factors can limit treatment options for migraine. Rimegepant is an orally administered small-molecule calcitonin gene-related peptide receptor antagonist that does not induce vasoconstriction. The aim of these post hoc subgroup analyses was to assess the safety of rimegepant according to CV risk.

Methods: In a multicenter, long-term, open-label, phase II/III safety study, participants with a history of 2-14 migraine attacks per month of moderate or severe pain intensity self-administered rimegepant 75 mg, orally, to treat migraine up to once daily for up to 52 weeks. Uncontrolled, unstable, or recently diagnosed CV disease was part of the exclusion criteria. Safety was assessed across subgroups according to number of CV risk factors (0, 1, or ≥ 2) and Framingham Risk Score (< 10% or ≥ 10%).

Results: Of 1800 treated participants, 28.8% had one CV risk factor and 12.1% had ≥ 2 CV risk factors; 7.0% had Framingham Risk Score ≥ 10%. Across the subgroups with 0, 1, and ≥ 2 CV risk factors and Framingham Risk Score < 10% and ≥ 10%, respectively, proportions of participants reporting adverse events (AEs; 59.6%, 61.4%, 62.2%, 59.9%, 67.5%) and serious AEs (2.7%, 2.5%, 2.3%, 2.6%, 2.4%) were consistent, and AEs leading to study drug discontinuation were low (1.9%, 3.1%, 5.5%, 2.5%, 4.8%).

Conclusions: Rimegepant showed favorable safety and tolerability in adults with migraine and CV risk factors, including those with moderate to high CV risk.

Trial registration: ClinicalTrials.gov NCT03266588.

Fibromyalgia (FM) is a complex and common syndrome characterized by chronic widespread pain, fatigue, sleep disturbances, and various functional symptoms without clear structural or pathological causes. Affecting approximately 1-5% of the global population, with a higher prevalence in women, FM significantly impacts patients' quality of life, often leading to considerable healthcare costs and loss of productivity. Despite its prevalence, the etiology of FM remains elusive, with genetic, environmental, and psychological factors, including nutrition, being implicated. Currently, no universally accepted treatment guidelines exist, and management strategies are often symptomatic. This narrative review explores the potential of a neuronutritional approach to FM management. It synthesizes existing research on the relationship between FM and nutrition, suggesting that dietary interventions could be a promising complementary treatment strategy. Various nutritional interventions, including vitamin D, magnesium, iron, and probiotics supplementation, have shown potential in reducing FM symptoms, such as chronic pain, anxiety, depression, cognitive dysfunction, sleep disturbances, and gastrointestinal issues. Additionally, weight loss has been associated with reduced inflammation and improved quality of life in FM patients. The review highlights the anti-inflammatory benefits of plant-based diets and the low-FODMAPs diet, which have shown promise in managing FM symptoms and related gastrointestinal disorders. Supplements such as vitamin D, magnesium, vitamin B12, coenzyme Q10, probiotics, omega-3 fatty acids, melatonin, S-adenosylmethionine, and acetyl-L-carnitine are discussed for their potential benefits in FM management through various mechanisms, including anti-inflammatory effects, modulation of neurotransmitters, and improvement of mitochondrial function. In conclusion, this review underscores the importance of considering neuronutrition as a holistic approach to FM treatment, advocating for further research and clinical trials to establish comprehensive dietary guidelines and to optimize management strategies for FM patients.

Introduction: Central post-stroke pain (CPSP) is a common type of central neuropathic pain (CNeP) that can occur following the onset of stroke. The oral gabapentinoid mirogabalin besylate (mirogabalin) is a selective α₂δ ligand that is effective for the treatment of CNeP, including CPSP. However, it is unknown whether the analgesic effect of mirogabalin on CPSP varies in patients with different background factors.

Methods: This was a post hoc subgroup analysis of a multinational, open-label, long-term phase 3 study of mirogabalin for the treatment of CNeP conducted between March 2019 and December 2020. Data from patients with CPSP were stratified by type of stroke (ischemic or hemorrhagic), stroke location (thalamus, putamen, brainstem, or other), presence/absence of motor weakness, median time since stroke (≥ 59 or < 59 months), and median duration of CPSP (≥ 55.5 or < 55.5 months). Efficacy was assessed with the short-form McGill Pain Questionnaire (SF-MPQ), and treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were recorded.

Results: This subanalysis included all 94 patients with CPSP from the phase 3 study; all were Japanese, and the mean age was 65.3 years. The least squares mean change [95% confidence interval] in SF-MPQ visual analog scale (VAS) score from baseline at week 52 (last observation carried forward) was - 17.0 [- 22.1, - 11.9] mm. Among the subgroups, least squares mean changes in SF-MPQ VAS scores were not different. Most TEAEs were mild or moderate; severe TEAEs occurred in six patients (6.4%). Somnolence (25.5%), peripheral edema (13.8%), dizziness (11.7%), and weight gain (6.4%) were the most common ADRs, and the types and frequencies of ADRs were similar among subgroups.

Conclusion: Mirogabalin was generally effective and well tolerated in patients with CPSP, regardless of background factors such as stroke type or location, presence/absence of motor weakness, time since stroke, and duration of CPSP.

Trial registration: Trial registration number NCT03901352.

Introduction: Erenumab-aooe is approved for the preventive treatment of migraine in adults. Recent publications have evaluated migraine medication use during the 6 months after starting erenumab, but longer-term follow-up data are limited. The objective of this study was to describe 12-month medication use and changes in healthcare resource utilization (HRU) and associated direct costs among patients initiating erenumab.

Methods: We identified adult patients with an erenumab claim in the Merative MarketScan Commercial and Medicare Databases from May 2018 through September 2019. Eligible patients had ≥ 12 months of continuous medical and pharmacy coverage before (pre-index period) and after (post-index period) the index date (first erenumab claim) in addition to pre-index evidence of migraine. Patients were stratified by post-index-period adherence to erenumab, defined as ≥ 80% of days covered (adherent) or < 80% of days covered (non-adherent). Outcomes were measured pre- and post-index, and differences between these periods were described.

Results: Among 7528 eligible patients, the mean (standard deviation) age was 45.1 (11.4) years and 85.4% were female; 38.5% of patients were adherent to erenumab. Most patients used acute or traditional migraine-preventive medications pre-index, with reductions in use observed post-index (acute medication was used by 95.6% of patients pre-index, compared to 92.3% post-index; traditional preventive medication was used by 89.6% of patients pre-index, compared to 81.9% post-index). Reductions were observed for HRU of emergency room visits (- 3.8%) and brain- and other head-imaging studies (- 7.5%). Overall costs associated with acute and traditional preventive medications were reduced (- $764), but costs for HRU increased slightly ($76). When stratifying by adherence and combining costs for acute and traditional preventive medications and HRU, adherent patients had cost decreases (- $1947), while non-adherent patients had cost increases ($101).

Conclusion: Most patients initiating erenumab had prior use of acute and traditional migraine-preventive therapies. The reduction in acute and traditional migraine-preventive medication use and HRU over the 12-month follow-up supports the long-term clinical benefits of erenumab in the real-world setting.

Introduction

Migraine is under-diagnosed and under-treated. Many people with migraine do not seek medical care, and those who do may initially receive a different diagnosis and/or be dissatisfied with provided care on their journey before treatment with a CGRP-mAb (calcitonin-gene-related-peptide monoclonal antibody).

Methods

This is a cross-sectional, self-reported, online survey of subjects in Lilly’s Emgality^® Patient Support Program in 2022. Questionnaires collected insights into subjects’ prior experiences with migraine and interactions with healthcare professionals before receiving CGRP-mAbs.

Results

Of the 250 participants with episodic and 250 with chronic migraine, 90% were female and white with a mean age of 26.2 years (± 11.9) at diagnosis and 40.6 (± 12.0) years at survey enrollment. Many participants (71%) suspected they had migraine before diagnosis, with 31% reluctant to seek help. Of these, approximately one-third were unaware of treatment, did not think that a physician could do anything more for migraine, would not take them seriously, or were reluctant due to a previous unhelpful experience. Participants mainly received information from friends/family (47%) or the internet (28%). Participants initially sought treatment due to an increase in migraine frequency (77%), attacks interfering with work or school (75%), or increased pain intensity (74%). Subjects saw a mean of 4.1 (± 4.3) healthcare providers before migraine diagnosis, and 20% of participants previously received a different diagnosis. Participants reported migraine causes included stress/anxiety/depression (42%), hormonal changes (30%), nutrition (20%), and weather (16%). Acute treatment of migraine included prescription (82%) and over-the-counter (50%) medications, changes in nutrition (62%), adjusting fluid intake (56%), and relaxation techniques (55%). Preventive medications included anticonvulsants (61%), antidepressants (44%), blood pressure-lowering medications (43%), and botulinum toxin A injections (17%). Most discontinuations were due to lack of efficacy or side effects.

Conclusion

People with migraine describe reluctance in seeking health care, and misunderstandings seem common especially in the beginning of their migraine journey.

Graphical abstract available for this article.

Graphical Abstract