Subcutaneous Oxytocin Injection Reduces Heat Pain: A Randomized-Controlled Trial.

Oxytocin (OT) is a neuropeptide broadly implicated in social relationships and behavior. OT also exerts antinociceptive and pain-reducing effects in both humans and rodents. Recent research in rodents demonstrates that these effects can be peripheral and local. In human studies, intravenous OT has reduced visceral pain, and subcutaneous injection of OT has reduced postsurgical pain. However, the local effects of subcutaneous OT on experimental pain have not been studied. We conducted a 2-session crossover study during which healthy adults received a subcutaneous injection of synthetic OT (4 mcg/2 mL) or saline placebo (isotonic saline 2 mL), in a randomized and double-blinded manner. Eighteen participants completed full study procedures. We hypothesized that 10 minutes after injection, OT would reduce measures of acute mechanical pain, pressure pain, and heat pain perception. Subcutaneous OT significantly reduced ratings of heat pain intensity and unpleasantness (both P < .01), but did not alter mechanical pain, pressure pain, or heat pain threshold (all P > .05). Changes in heat pain were observed only on the injected arm and not on the contralateral arm, confirming a localized mechanism. These findings confirm the ability of OT in or near the skin to modulate nociceptive processes in cutaneous tissues in human adults, opening exciting avenues for further mechanistic research as well as potential clinical applications for acute pain. PERSPECTIVE: This randomized-controlled trial showed that a subcutaneous injection of OT could reduce perception of heat pain tested with a thermode. OT did not alter mechanical or pressure pain or thresholds for perceiving heat pain. These findings are relevant to scientists and clinicians seeking nonaddictive local drug treatments for pain.

Migraine Prevalence, Environmental Risk, and Comorbidities in Men and Women Veterans.

Importance: Migraine is a prevalent and debilitating condition that substantially impacts quality of life. Investigating migraine prevalence, associated comorbidities, and potential military service exposures in veterans, focusing on gender differences, is crucial for targeted interventions and management strategies. Objective: To determine the prevalence of migraine, associated health comorbidities, and potential military service and environmental exposures among men and women US veterans using a large-scale epidemiological sample from the Million Veteran Program (MVP). Design, Setting, and Participants: This cross-sectional study analyzed self-report survey data from the MVP, a large epidemiological sample of US veterans that was started in 2011 and has ongoing enrollment. Eligible participants were selected from the MVP database in 2023. The study included 491 604 veterans to examine migraine prevalence, health comorbidities, demographic characteristics, military service history, and environmental exposures. Data were analyzed from December 2022 to July 2023. Exposures: Military service and environmental factors, such as chemical or biological warfare exposure, were considered. Main Outcomes and Measures: The primary outcome was migraine prevalence among men and women veterans, assessed through self-reported diagnoses. Secondary outcomes included the association between migraine and health comorbidities, demographic characteristics, military service history, and environmental exposures. Results: Of the 491 604 veterans included in this study, 450 625 (91.8%) were men and 40 979 (8.2%) were women. The lifetime prevalence of migraine was significantly higher in women (12 324 of 40 979 [30.1%]) than in men (36 816 of 450 625 [8.2%]). Migraine prevalence varied by race and ethnicity, with the highest prevalence in Hispanic or Latinx women (1213 of 3495 [34.7%]). Veterans with migraine reported worse general health, higher levels of pain, increased pain interference with work, a higher likelihood of psychiatric and neurological health conditions, and greater lifetime opioid use. Specific aspects of military service, including service post-September 2001 and deployment in Operation Enduring Freedom and Operation Iraqi Freedom, and environmental factors, including Agent Orange, chemical and biological welfare, and antinerve agent pills history, were significantly associated with migraine prevalence. Conclusions and Relevance: In this cross-sectional study of migraine, the results highlighted gender differences in migraine prevalence and associated health comorbidities among US veterans. The findings emphasized the need for interdisciplinary approaches to migraine management, increased awareness and education efforts, and population-based screening strategies, particularly for women and Hispanic veterans who are at greater risk. Our findings encourage further research into tailored interventions for specific subpopulations and the impact of military service and environmental exposures on migraine and related health conditions.

Vaporized Cannabis versus Placebo for Acute Migraine: A Randomized Controlled Trial.

Background: Preclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine. Methods: In this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to 4 separate migraine attacks, 1 each with vaporized 1) 6% Δ9-tetrahydrocannabinol (THC-dominant); 2) 11% cannabidiol (CBD-dominant); 3) 6% THC+11% CBD; and 4) placebo cannabis flower in a randomized order. Washout period between treated attack was ≥1 week. The primary endpoint was pain relief and secondary endpoints were pain freedom and most bothersome symptom (MBS) freedom, all assessed at 2 hours post-vaporization. Results: Ninety-two participants were enrolled and randomized, and 247 migraine attacks were treated. THC+CBD was superior to placebo at achieving pain relief (67.2% vs 46.6%, Odds Ratio [95% Confidence Interval] 2.85 [1.22, 6.65], p=0.016), pain freedom (34.5% vs. 15.5%, 3.30 [1.24, 8.80], p=0.017) and MBS freedom (60.3% vs. 34.5%, 3.32 [1.45, 7.64], p=0.005) at 2 hours, as well as sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours. THC-dominant was superior to placebo for pain relief (68.9% vs. 46.6%, 3.14 [1.35, 7.30], p=0.008) but not pain freedom or MBS freedom at 2 hours. CBD-dominant was not superior to placebo for pain relief, pain freedom or MBS freedom at 2 hours. There were no serious adverse events. Conclusions: Acute migraine treatment with 6% THC+11% CBD was superior to placebo at 2 hours post-treatment with sustained benefits at 24 and 48 hours.

Debunking myths in headache diagnosis for the pain practitioner.

With headache being one of the most common chief complaints, it is essential for pain practitioners to interpret and differentiate a variety of headache characteristics to accurately diagnose and treat specific headache disorders. Certain misconceptions often lead to misdiagnosis. This article presents and discusses six myths about several common headache disorders (migraine, tension-type headache, cluster headache, cervicogenic headache, sinus headache, and occipital neuralgia) often encountered in clinical practice. The discussion is based primarily on the International Classification of Headache Disorders, 3rd edition and the latest studies. Recognizing and understanding the intricacies behind key headache diagnoses will help providers devise appropriate plans to better care for their patients.

Use of spinal cord stimulation in treatment of intractable headache diseases.

Headache diseases remain one of the leading causes of disability in the world. With the development of neuromodulation strategies, high cervical spinal cord stimulation (hcSCS) targeting the trigeminocervical complex has been deployed to treat refractory headache diseases. In this article, we review the proposed mechanism behind hcSCS stimulation, and the various studies that have been described for the successful use of this treatment strategy in patients with chronic migraine, cluster headache, and other trigeminal autonomic cephalalgias.

Rate and Predictors of Patients with Chronic Pain Establishing Care with Pain Psychology Following Pain Physician Referral.

OBJECTIVE: To determine, among patients with chronic pain who had received pain physician referral to pain psychology, the rate of establishing care and factors related to establishing care with pain psychology. DESIGN: Retrospective study. SETTING: Academic tertiary care center. SUBJECTS: Patients from the University of California, San Diego (UCSD) Center for Pain Medicine. METHODS: This was an institutional review board-approved, retrospective study of 150 consecutive referrals of unique patients from UCSD Pain Medicine to UCSD Pain Psychology. RESULTS: Of 150 patients referred to pain psychology, 74 (49.3%) established care with pain psychology. Of 98 patients who had previously seen mental health services, 58 established care with pain psychology (59.2%; 95% confidence interval [CI]: 49% to 69%), whereas of 52 patients who had not previously seen mental health services, 16 established care with pain psychology (30.8%; 95% CI: 18% to 43%) (odds ratio [OR] 3.26; 95% CI: 1.60 to 6.66). In the patient subset with depression and/or anxiety, of 82 patients who had previously seen mental health services, 47 established care with pain psychology (57.3%; 95% CI: 47% to 68%), whereas of 20 patients who had not previously seen mental health services, three established care with pain psychology (15%; 95% CI: -1% to 31%) (OR 7.61; 95% CI: 2.07 to 28.01). Of 96 patients referred for general pain psychology evaluations, 43 established care (45%; 95% CI: 35% to 55%), whereas of 38 patients referred for preprocedural evaluation for an implantable device, 24 established care (63%; 95% CI: 48% to 78%). CONCLUSION: Patients are significantly more likely to establish care with pain psychology if they have previously seen a mental health professional. This was even more marked among the patient subset with a history of depression and/or anxiety who had engaged in mental health services than among those with a history of depression and/or anxiety who had not engaged in mental health services. Whether referral was for general psychological evaluation or preprocedural evaluation for an implantable device did not significantly influence whether patients established care. Targeted interventions are needed to improve the likelihood of patients engaging with pain psychology services.

Peripheral Nerve Stimulation for Chronic Pain and Migraine: A Review.

Interventional pain procedures offer treatments for chronic pain conditions refractory to conservative measures. Neuromodulation, including peripheral nerve stimulation (PNS), applies electrical stimuli to neural structures to treat pain. Here we review the literature on PNS for various chronic pain conditions including neuropathic pain, postamputation pain, musculoskeletal pain, migraine, and pelvic pain.

Occipital Headache Evaluation and Rates of Migraine Assessment, Diagnosis, and Treatment in Patients Receiving Greater Occipital Nerve Blocks in an Academic Pain Clinic.

OBJECTIVE: Diagnosis of patients with occipital headache can be challenging, as both primary and secondary causes must be considered. Our study assessed how often migraine is screened for, diagnosed, and treated in patients receiving greater occipital nerve blocks (GONBs) in a pain clinic. DESIGN: Institutional review board-approved, retrospective observational study. SETTING: Academic multidisciplinary pain clinic. SUBJECTS: One hundred forty-three consecutive patients who received GONBs. RESULTS: About 75% of patients had been evaluated by neurologists and about 25% by non-neurologist pain specialists only, and 62.2% of patients had photophobia, phonophobia, and nausea assessed. Compared with patients who had been evaluated by non-neurologists, patients who had been evaluated by a neurologist were more likely to have photophobia, phonophobia, and nausea assessed (75.9% vs 20.0%, odds ratio [OR] 12.6, 95% confidence interval [CI] 4.90 to 32.2); more likely to be diagnosed with migraine (48.1% vs 14.3%, OR 5.6, 95% CI 2.0 to 15); less likely to be diagnosed with occipital neuralgia (39.8% vs 65.7%, OR 0.3, 95% CI 0.2 to 0.8); and equally likely to be diagnosed with cervicogenic headache (21.3% vs 25.7%, OR 0.8, 95% CI 0.3 to 1.9). Among patients diagnosed with migraine, 82.5% received acute migraine treatment, 89.5% received preventive migraine treatment, and 52.6% were documented as receiving migraine lifestyle counseling. CONCLUSIONS: Of the patients in this study who had occipital headache and received GONBs, 62.2% were assessed for migraine, and most received appropriate acute, preventive, and lifestyle treatments when diagnosed. Patients seen by neurologists were significantly more likely to be screened for and diagnosed with migraine than were those evaluated by non-neurologist pain medicine specialists only. All clinicians should remain vigilant for migraine in patients with occipital headache.

Percutaneous Interventional Strategies for Migraine Prevention: A Systematic Review and Practice Guideline.

OBJECTIVE: To systematically evaluate the efficacy and effectiveness of percutaneous interventional treatments for prevention of migraine through a qualitative and (when possible) quantitative analysis. METHODS: An expert panel was asked to develop recommendations for the multidisciplinary preventive treatment of migraine, including interventional strategies. The committee conducted a systematic review and (when evidence was sufficient) a meta-analytic review by using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria and the modified Cochrane Risk of Bias analysis available in the Covidence data management program. Clinical questions addressed adults with migraine who should be offered prevention. Examined outcomes included headache days, acute medication use, and functional impairment. Acute management of migraine was outside the scope of this guideline. RESULTS: The committee screened 1,195 studies and assessed 352 by full text, yielding 16 randomized controlled trials that met the inclusion criteria. RECOMMENDATIONS AND CONCLUSIONS: As informed by evidence related to the preselected outcomes, adverse event profile, cost, and values and preferences of patients, onabotulinumtoxinA received a strong recommendation for its use for chronic migraine prevention and a weak recommendation against its use for episodic migraine prevention. Greater occipital nerve blocks received a weak recommendation for their use for chronic migraine prevention. For greater occipital nerve block, steroid received a weak recommendation against its use vs the use of local anesthetic alone. Occipital nerve with supraorbital nerve blocks, sphenopalatine ganglion blocks, cervical spine percutaneous interventions, and implantable stimulation all received weak recommendations for their use for chronic migraine prevention. The committee found insufficient evidence to assess trigger point injections in migraine prevention and highly discouraged the use of intrathecal medication.

Widespread Pressure Delivered by a Weighted Blanket Reduces Chronic Pain: A Randomized Controlled Trial.

Pleasant sensation is an underexplored avenue for modulation of chronic pain. Deeper pressure is perceived as pleasant and calming, and can improve sleep. Although pressure can reduce acute pain, its effect on chronic pain is poorly characterized. The current remote, double-blind, randomized controlled trial tested the hypothesis that wearing a heavy weighted blanket - providing widespread pressure to the body - relative to a light weighted blanket would reduce ratings of chronic pain, mediated by improvements in anxiety and sleep. Ninety-four adults with chronic pain were randomized to wear a 15-lb. (heavy) or 5-lb. (light) weighted blanket during a brief trial and overnight for one week. Measures of anxiety and chronic pain were collected pre- and post-intervention, and ratings of pain intensity, anxiety, and sleep were collected daily. After controlling for expectations and trait anxiety, the heavy weighted blanket produced significantly greater reductions in broad perceptions of chronic pain than the light weighted blanket (Cohen's f = .19, CI [-1.97, -.91]). This effect was stronger in individuals with high trait anxiety (P = .02). However, weighted blankets did not alter pain intensity ratings. Pain reductions were not mediated by anxiety or sleep. Given that the heavy weighted blanket was associated with greater modulation of affective versus sensory aspects of chronic pain, we propose that the observed reductions are due to interoceptive and social/affective effects of deeper pressure. Overall, we demonstrate that widespread pressure from a weighted blanket can reduce the severity of chronic pain, offering an accessible, home-based tool for chronic pain. The study purpose, targeted condition, study design, and primary and secondary outcomes were pre-registered in ClinicalTrials.gov (NCT04447885: "Weighted Blankets and Chronic Pain"). PERSPECTIVE: This randomized-controlled trial showed that a 15-lb weighted blanket produced significantly greater reductions in broad perceptions of chronic pain relative to a 5-lb weighted blanket, particularly in highly anxious individuals. These findings are relevant to patients and providers seeking home-based, nondrug therapies for chronic pain relief.

Lasmiditan for the acute treatment of migraine.

Migraine is a leading cause of morbidity and disability worldwide. Triptans were the first migraine-specific drug class developed and have proven efficacy in treatment of this neurological disease. They are however contraindicated in patients with cardiovascular disease and possibly others, owning to their vasoconstrictive properties. This review will focus on lasmiditan, which has been called the first 'ditan' and 'neurally acting anti-migraine agent', designed to selectively agonize the serotonin 5-HT1F receptor subtype, providing anti-migraine effects without concomitant vasoconstriction. To date, lasmiditan has proven safe and effective for the acute treatment of migraine in two Phase II and four Phase III trials. Post hoc analysis revealed that the majority of treatment-emergent adverse events were CNS-related, mild-to-moderate in severity and self-limiting. The US FDA label recommends that patients not drive or operate machinery until at least 8 h after taking each dose of lasmiditan.

Lay abstract Migraine is a leading cause of pain and disability worldwide. Triptans (e.g., sumatriptan) were the first migraine-specific drug class developed and have proven to be effective treatments. Triptans are however contraindicated in patients with heart disease and possibly in some subsets of migraine, due to vasoconstriction concerns. This review will focus on lasmiditan, the first 5-HT_1F receptor agonist or 'ditan'. It does not carry vasoconstrictive concerns and is safe to use in patients who cannot take triptans. To date, lasmiditan has proven safe and effective for the acute treatment of migraine in multiple medical studies. Data from these studies indicates that the most common adverse effects from lasmiditan were dizziness, tingling and sleepiness. These symptoms were generally mild-to-moderate in severity and self-limiting. The US FDA label recommends that patients not drive or operate machinery until at least 8 h after taking each dose of lasmiditan.

The American Society of Pain and Neuroscience (ASPN) Practical Guidelines to Study Design and Scientific Manuscript Preparation in Neuromodulation.

BACKGROUND: Healthcare clinical and even policy decisions are progressively made based on research-based evidence. The process by which the appropriate trials are developed and well-written manuscripts by means of evidence-based medicine recommendations has resulted in unprecedented necessity in evidence-based medicine in neuromodulation. METHODS: The essential considerations in the planning of neuromodulation research are discussed in the light of available scientific literature as well as the authors' scientific expertise regarding research study design and scientific manuscript preparation. CONCLUSION: This article should enable the reader to understand how to appropriately design a clinical research study and prepare scientific manuscripts. The high-quality and well-designed studies, when performed and reported effectively, support evidence-based medicine and foster improved patient outcomes.

The Effectiveness of Intraosseous Basivertebral Nerve Radiofrequency Neurotomy for the Treatment of Chronic Low Back Pain in Patients with Modic Changes: A Systematic Review.

OBJECTIVE: Determine the effectiveness of intraosseous basivertebral nerve radiofrequency neurotomy for the treatment of chronic low back pain with type 1 or 2 Modic changes. DESIGN: Systematic review. POPULATION: Persons aged ≥18 years with chronic low back pain with type 1 or 2 Modic changes. INTERVENTION: Intraosseous basivertebral nerve radiofrequency neurotomy. COMPARISON: Sham, placebo procedure, active standard care treatment, or none. OUTCOMES: The primary outcome of interest was the proportion of individuals with ≥50% pain reduction. Secondary outcomes included ≥10-point improvement in function as measured by Oswestry Disability Index as well as ≥2-point reduction in pain score on the Visual Analog Scale or Numeric Rating Scale, and decreased use of pain medication. METHODS: Three reviewers independently assessed publications before May 15, 2020, in MEDLINE and Embase and the quality of evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation framework. RESULTS: Of the 725 publications screened, seven publications with 321 participants were ultimately included. The reported 3-month success rate for ≥50% pain reduction ranged from 45% to 63%. Rates of functional improvement (≥10-point Oswestry Disability Index improvement threshold) ranged from 75% to 93%. For comparison to sham treatment, the relative risk of treatment success defined by ≥50% pain reduction and ≥10-point Oswestry Disability Index improvement was 1.25 (95% confidence interval [CI]: .88-1.77) and 1.38 (95% CI: 1.10-1.73), respectively. For comparison to continued standard care treatment the relative risk of treatment success defined by ≥50% pain reduction and ≥10-point Oswestry Disability Index improvement was 4.16 (95% CI: 2.12-8.14) and 2.32 (95% CI: 1.52-3.55), respectively. CONCLUSIONS: There is moderate-quality evidence that suggests this procedure is effective in reducing pain and disability in patients with chronic low back pain who are selected based on type 1 or 2 Modic changes, among other inclusion and exclusion criteria used in the published literature to date. Success of the procedure appears to be dependent on effective targeting of the BVN. Non-industry funded high-quality, large prospective studies are needed to confirm these findings.