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Yashar Eshraghi,1– 3 Krishnan Chakravarthy,4,5 Natalie H Strand,6 Prasad Shirvalkar,7 Nathaniel M Schuster,4 Rany T Abdallah,8 Ricardo Vallejo,9,10 Dawood Sayed,11 David Kim,11 Chong Kim,12 Kathleen Meacham,13 Timothy Deer14,15 On Behalf of Translational Research Committee American Society of Pain and Neuroscience (ASPN)1Department of Anesthesia, Interventional Pain Management, Ochsner Health System, New Orleans, LA, USA; 2University of Queensland Ochsner Clinical School. Academics Department, Ochsner Health System, New Orleans, LA, USA; 3Louisiana State University School of Medicine, New Orleans, LA, USA; 4Division of Pain Medicine, Department of Anesthesiology, University of California San Diego, San Diego, CA, USA; 5VA San Diego Health Care, San Diego, CA, USA; 6Division of Pain Medicine, Department of Anesthesiology, Mayo Clinic, Phoenix, Arizona, USA; 7Department of Anesthesiology (Pain Management), Department of Neurology, UCSF School of Medicine, San Francisco, CA, USA; 8Center for Interventional Pain and Spine, Wilmington, DE, USA; 9National Spine and Pain Center, Bloomington, IL, USA; 10Psychology Department, Illinois Wesleyan University, Bloomington, IL, USA; 11University of Kansas Medical Center, Kansas City, KS, USA; 12Departments of Physical Medicine and Rehabilitation and Anesthesiology, Case Western Reserve University/MetroHealth, Cleveland, OH, USA; 13Division of Pain Management, Department of Anesthesiology, Washington University School of Medicine, St Louis, MO; 14The Spine and Nerve Center of the Virginias, Charleston, WV, USA; 15West Virginia University, School of Medicine, Charleston, WV, USACorrespondence: Yashar Eshraghi Email Yashar.Eshraghi@gmail.comBackground: 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.Keywords: research, study design, neuromodulation, neurostimulation, clinical evidence review

Jessica C Oswald, Nathaniel M Schuster UCSD Center for Pain Medicine, La Jolla, CA, USA Abstract: Now that the vascular hypothesis of migraine is no longer the prevailing theory of migraine pathogenesis, there is interest in developing acute migraine treatments that act exclusively on non-vascular targets. There is a large percentage of non-responders to current acute migraine treatments and the vasoconstriction associated with triptans limit their use in patients with pre-existing cardiovascular risk factors. Preferential 5-HT1F agonists have shown promising results in in vitro and early proof-of-concept trials. Lasmiditan, a highly selective 5-HT1F agonist, has completed two Phase III randomized, double blind, placebo-controlled clinical trials, with a third – a long-term, open-label safety study – still underway. Research to date suggests lasmiditan lacks vasoconstrictive properties and may be a safe and effective treatment option in patients refractory to current acute migraine medications or who have cardiovascular risk factors. Keywords: lasmiditan, 5HT-1F, migraine, headache, serotonin

Objective: Opioid and cannabinoid therapies for chronic pain conditions including neuropathic pain are controversial. Understanding patient and prescribing factors contributing to risks and implementing risk mitigation strategies optimizes outcomes., Latest Developments: The ongoing transformation from a biomedical model of pain care toward a biopsychosocial model has been accompanied by a shift away from opioid therapy for pain, in particular for chronic pain. Opioid overdose deaths and opioid use disorder have greatly increased in the last several decades, initially because of increases in opioid prescribing and more recently associated with illicit drug use, in particular fentanyl derivatives. Opioid risk mitigation strategies may reduce risks related to opioid prescribing and tapering or discontinuation. Opioid therapy guidelines from the Centers for Disease Control and Prevention have become the consensus best practice for opioid therapy. Regulatory agencies and licensing medical boards have implemented restrictions and other mandates regarding opioid therapy. Meanwhile, interest in and use of cannabinoids for chronic pain has grown in the United States., Essential Points: Opioid therapy is generally not recommended for the chronic treatment of neuropathic pain conditions. Opioids may be considered for temporary use in patients with severe pain related to selected neuropathic pain conditions (such as postherpetic neuralgia), and only as part of a multimodal treatment regimen. Opioid risk mitigation strategies include careful patient selection and evaluation, patient education and informed consent, querying the state prescription drug monitoring programs, urine drug testing, and issuance of naloxone as potential rescue medication. Close follow-up when initiating or adjusting opioid therapy and frequent reevaluation during long-term opioid therapy is required. There is evidence for the efficacy of cannabinoids for neuropathic pain, with meaningful response rates in select patient populations., (Copyright © 2024 American Academy of Neurology.)

Objective: This article reviews pain disorders encountered in pediatric neurology practice and provides current information regarding the assessment and treatment of pediatric chronic pain., Latest Developments: Data about pediatric pain management remain sparse, owing to a dearth of controlled trials and longitudinal studies in these patients. However, the field of pain management and understanding of central and peripheral pain processing has expanded to allow more effective treatment of a broad group of children and adolescents with pain associated with neurologic disease. Neuroimaging visualizes sensory and nonsensory systems, and genetic markers of sensitivity and disease may guide specific therapy. The concept of central sensitization in chronic pain disorders has supported the development of multidisciplinary paradigms for the comprehensive care of these patients., Essential Points: Pain involves sensory activation and central nervous system modulation in pediatric patients. Pediatric neurologists should be prepared to define, investigate, and treat pain disorders in this complex patient population. Appropriate interventions during childhood may attenuate or prevent chronic pain later in life. Current interventions include behavioral, physical, and pharmacologic approaches, as well as potential noninvasive tools for neuromodulation. Research is progressing in sensory measurement, neuroimaging, genetics, and neuroinflammation to guide future targeted therapies., (Copyright © 2024 American Academy of Neurology.)

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., (Published by Elsevier Inc.)

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., Competing Interests: Competing interests: Within the past 24 months, HY has received funding from NIH (R44NS115460); institutional support for serving as an investigator from Teva, Abbvie, Trillen, Thermaquil; consultant fees from Salvia, Pfizer, Cerenovus; and royalties from Cambridge University Press and MedLink. NS has received compensation from Eli Lilly & Co., Averitas, ShiraTronics, Syneos, Schedule 1 Therapeutics, and Vectura Fertin and research funding from Migraine Research Foundation, Novaremed, UCSD Academic Senate, UCSD Department of Anesthesiology RAG, and NIH CTSA Grant UL1TR000100. SS received consulting honorarium from Allergan., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Representatives from the Spine Intervention Society (SIS) Standards Division and Evidence Analysis Committee have developed the following best practice recommendations for the performance of interventional pain procedures in the setting of a local anesthetic shortage. The practice advisory has been endorsed by SIS, the American Academy of Pain Medicine, the American College of Radiology, the American Society of Neuroradiology, the American Society of Spine Radiology, the North American Neuromodulation Society, the North American Spine Society, and the Society of Interventional Radiology, who support the following best practice recommendations and statements for the performance of intra-articular, extra-articular, paraspinal, and epidural injections in the setting of a local anesthetic shortage. 1.Use of preservative-containing local anesthetics is discouraged in the performance of neuraxial procedures where the injectate may enter the epidural (or intrathecal) spaces.2.When performing procedures with risk of arterial injection, ropivacaine should not be mixed with dexamethasone and injected due to the risk of crystallization and embolization.3.Physicians should not withdraw directly from vials of local anesthetic for multiple patients due to infection risk as per Centers for Disease Control and Prevention (CDC) and Joint Commission guidelines [1].4.Only pharmacists may repackage local anesthetic vials for multiple patients. This must be performed under strict, sterile conditions and only in times of critical need. In such situations, physicians must adhere to the beyond-use-date and storage conditions on the repackaged label [2,3].5.Joint, tendon, bursa, and/or ligament injections may be performed with local anesthetic with or without preservative.6.Interventional pain physicians should weigh the relative chondrotoxicity risks associated with each anesthetic when performing joint injections.7.Topical anesthetics, infiltration with diphenhydramine, and nonpharmacologic therapies ( i.e., cognitive behavioral therapy, guided imagery, virtual reality, mechanodesensitization) may be used as alternatives to skin infiltration of local anesthetic for reducing procedural pain.8.Use of small-gauge needles (25 gauge or thinner) mitigates the need for local anesthetic prior to needle insertion.9.For local anesthetic infiltration prior to insertion of large bore needles or incision, 0.5% lidocaine may be as effective as 1%, and for that reason current supplies of lidocaine can be stretched by dilution with normal saline.10.If using an ester local anesthetic due to an amide local anesthetic shortage, interventional pain physicians should be aware (as always) of the potential for an allergic reaction and should be able to respond accordingly.11.Local anesthetic systemic toxicity (LAST) differs between the varying local anesthetics, and interventional pain physicians should be well acquainted with these differences when switching between local anesthetics. Physicians should carefully weigh the risks and benefits of performing procedures without local anesthetic or using an alternative agent in the context of each unique patient's situation and should involve patients in shared decision making before proceeding. Procedures should be performed following Spine Intervention Society Guidelines [4]. The physician should confirm placement of the needle in at least two imaging planes. Please refer to the SIS Practice Guidelines for the full details and standards related to each unique procedure [4]., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Representatives from the Spine Intervention Society (SIS) and American Academy of Pain Medicine (AAPM) have developed the following best practice recommendations for the performance of interventional pain procedures in the setting of an iodinated contrast media shortage. The practice advisory has been endorsed by SIS, AAPM, American Academy of Physical Medicine and Rehabilitation (AAPMR), American Society of Neuroradiology (ASNR), American Society of Spine Radiology (ASSR), North American Neuromodulation Society (NANS), North American Spine Society (NASS), and Society of Interventional Radiology (SIR)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

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., Competing Interests: Disclosure S.C. Erosa, MD, R.S. Moheimani, MD, and M.E. Abraham, MD, have nothing to disclose. J.C. Oswald, MD, receives honorarium from Averitas Pharma. J.P. Castellanos, MD, is a scientific advisor for Tryp Therapeutics. N.M. Schuster, MD, receives research funding from Migraine Research Foundation; personal fees from Eli Lilly & Company, Lundbeck, Averitas, and UMEHEAL; and is on the editorial boards of Pain Medicine, Interventional Pain Medicine, and Annals of Headache Medicine., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

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-HT 1F 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.

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice., Competing Interests: EK and SK are employed by company SzeleSTIM GmbH. JS received honoraria from SzeleSTIM GmbH and owns patents in the field of the auricular vagus nerve stimulation. EK, SK, and JS are shareholders of SzeleSTIM GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer TS declared a shared affiliation, with no collaboration, with one of the authors HJ, to the handling editor at the time of review., (Copyright © 2021 Farmer, Strzelczyk, Finisguerra, Gourine, Gharabaghi, Hasan, Burger, Jaramillo, Mertens, Majid, Verkuil, Badran, Ventura-Bort, Gaul, Beste, Warren, Quintana, Hämmerer, Freri, Frangos, Tobaldini, Kaniusas, Rosenow, Capone, Panetsos, Ackland, Kaithwas, O'Leary, Genheimer, Jacobs, Van Diest, Schoenen, Redgrave, Fang, Deuchars, Széles, Thayer, More, Vonck, Steenbergen, Vianna, McTeague, Ludwig, Veldhuizen, De Couck, Casazza, Keute, Bikson, Andreatta, D'Agostini, Weymar, Betts, Prigge, Kaess, Roden, Thai, Schuster, Montano, Hansen, Kroemer, Rong, Fischer, Howland, Sclocco, Sellaro, Garcia, Bauer, Gancheva, Stavrakis, Kampusch, Deuchars, Wehner, Laborde, Usichenko, Polak, Zaehle, Borges, Teckentrup, Jandackova, Napadow and Koenig.)

Purpose of Review: Multiple Sclerosis (MS) is a chronic autoimmune disease with no curative treatment available. While recent years have ushered in many effective new disease-modifying therapies for MS, they have not obviated the need for symptomatic treatments for MS-related pain. In this review, we discuss available approaches to control pain, which is one of the most common complaints MS patients have., Recent Findings: The most recent research in this topic is directed towards non-pharmacologic interventions including water exercises, yoga and cannabis. More trials are being conducted on neuromodulation for MS-related neuropathic pain, including transcutaneous electrical nerve stimulation (TENS) and transcranial direct current stimulation (tDCS). Pain control for MS patients is challenging, considering the progressive and relapsing remitting nature of the disease, however, it is a very important aspect of it's management, as it improves mobility, exercise tolerance, concomitant depression and overall quality of life. Future research should focus on the use of neuromodulation in controlling MS pain.

Purpose of Review: Alterations in atmospheric pressure have been long associated with headaches. The purpose of this review article is to investigate the association of barometric pressure with headache, classifying into two broad categories primary headache disorders (barometric pressure triggering migraine or tension-type headache) and secondary headache disorders (barometric pressure triggering high-altitude headache and headache attributed to airplane travel), discussing the pathophysiology and possible treatments., Recent Findings: Multiple studies have been performed with inconsistent results regarding the directionality of the association between atmospheric pressure changes and triggering of primary headache disorders, chiefly headaches. Atmospheric pressure is also a trigger of two secondary headache disorders, i.e., high-altitude headache and headache attributed to airplane travel. Hypothesized mechanisms include excitation of neurons in trigeminal nucleus, central and peripheral vasoconstriction, barotrauma, and hypoxia. There are no randomized clinical trials regarding effective acute or preventive treatments. Greater understanding of pathophysiology may enable both acute and preventive treatments for headaches triggered by changes in barometric pressure. Further studies on the subject are needed.

Background: There are cases in the headache literature described as "cluster-migraine," but none of stereotyped cases of cluster headache evolving into status migrainosus. We believe this is the first documented case of "cluster-status migrainosus"., Case: A 54 year-old female hospital administrator presented with headaches with a unique periodicity and semiology that were acutely responsive to high-flow oxygen. She experienced cluster headache attacks every Thursday morning at 3-4 am, which would evolve into status migrainosus lasting through Sunday evening. These attacks were preceded by prodromal depressed mood changes and fluid retention, and later followed by postdromal euphoria and auto-diuresis. These attacks initially occurred every other week and progressed to weekly attacks for 1.5 years. These headaches did not respond to trials of propanolol, sodium valproate, topiramate, amitriptyline, gabapentin, and carbamazepine for preventive treatment or to oral sumatriptan and butalbital-acetaminophen-caffeine for acute treatment. We started her on high-flow 100% oxygen for cluster headache, which successfully aborted greater than 80% of her weekly cluster headache attacks and prevented them from evolving into status migrainosus., Conclusion: We believe this is the first case of "cluster-status migranosus" described in the medical literature. High-flow oxygen both aborted the cluster headaches and prevented the ensuing status migrainosus.

Purpose of Review: Recurrent painful ophthalmoplegic neuropathy (RPON), formerly known as ophthalmoplegic migraine, is an uncommon disorder with repeated episodes of ocular cranial nerve neuropathy associated with ipsilateral headache. This review discusses the clinical presentation, current understanding of the pathophysiology, key differential diagnoses, and evaluation and treatment of RPON., Recent Findings: The literature is limited due to the rarity of the disorder. Recent case reports and series continue to suggest the age of first attack is most often during childhood or adolescence as well as a female predominance. Multiple recent case reports and series demonstrate focal enhancement of the affected cranial nerve, as the nerve root exits the brainstem. This finding contributed to the current classification of the disorder as a neuropathy, with the present understanding that it is due to a relapsing-remitting inflammatory or demyelinating process. The link to migraine remains a cause of disagreement in the literature. RPON is a complex disorder with features of inflammatory neuropathy and an unclear association with migraine. Regardless, the overall prognosis is good for individual episodes, but permanent nerve damage may accumulate with repeated attacks. A better understanding of the pathogenesis is needed to clarify whether it truly represents a single disorder and to guide its treatment. Until that time, a combined approach with acute and preventive therapies can mitigate acute symptoms as well as attempt to limit recurrence of this disabling syndrome.

Calcitonin gene-related peptide (CGRP) is a signaling neuropeptide released from activated trigeminal sensory afferents in headache and facial pain disorders. There are a handful of CGRP-targeted therapies currently in phase 3 studies for migraine acute treatment or prevention. Currently, 4 monoclonal antibodies targeting either the CGRP ligand or receptor are being studied for migraine prevention: ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), and TEV-48125 (fremanezumab). Meanwhile, 1 small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine. Two of these anti-CGRP monoclonal antibodies are in clinical trials for cluster headache prevention as well. Several other small-molecular CGRP receptor antagonists are in earlier stages of development for acute migraine treatment or prevention. In this review, we will discuss the growing body of clinical trials studying CGRP-targeted therapies for migraine and cluster headache.

The primary headache disorders, which include migraine, cluster headache and tension-type headache, are among the most common diseases and leading causes of disability worldwide. The available treatment options for primary headache disorders have unsatisfactory rates of efficacy, tolerability and patient adherence. In this Review, we discuss promising new approaches for the prevention of primary headache disorders, such as monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor, and small-molecule CGRP receptor antagonists. Neuromodulation approaches employing noninvasive or implantable devices also show promise for treating primary headache disorders. Noninvasive treatments, such as transcranial magnetic stimulation and transcutaneous peripheral nerve stimulation, are delivered by devices that patients can self-administer. Implantable devices targeting the occipital nerves, sphenopalatine ganglion or high cervical spinal cord are placed using percutaneous and/or surgical procedures, and are powered either wirelessly or by surgically implanted batteries. These new and emerging treatments have the potential to address unmet patient needs and reduce headache-associated disability.

Migraine and cluster headache are common, episodic, often chronic and disabling disorders of the brain. Although there are many standard treatment techniques, none are ideal. This article reviews various novel pharmacologic and device-related treatments for migraine and cluster headache. Emphasis is given to recent advances in the development of monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) and its receptor, including promising results from phase 2 trials studying the safety and efficacy of LY2951742, ALD403 and TEV-48125, three anti-CGRP mAbs. Other new pharmacologic treatments discussed include the 5-HT1F receptor agonist lasmiditan and glial cell modulator ibudilast. Also reviewed is neuromodulation for migraine and cluster headache, including promising recent results of randomized controlled trials studying sphenopalatine ganglion stimulation, trigeminal nerve stimulation, transcutaneous vagus nerve stimulation, and transcranial magnetic stimulation. Finally, we discuss patch, inhaled, and intranasal methods of triptan and dihydroergotamine delivery.

Objective: To examine temporal and geographic associations between Google queries for health information and healthcare utilization benchmarks., Study Design: Retrospective longitudinal study., Methods: Using Google Trends and Google Insights for Search data, the search terms Lipitor (atorvastatin calcium; Pfizer, Ann Arbor, MI) and simvastatin were evaluated for change over time and for association with Lipitor revenues. The relationship between query data and community-based resource use per Medicare beneficiary was assessed for 35 US metropolitan areas., Results: Google queries for Lipitor significantly decreased from January 2004 through June 2009 and queries for simvastatin significantly increased (P <.001 for both), particularly after Lipitor came off patent (P <.001 for change in slope). The mean number of Google queries for Lipitor correlated (r = 0.98) with the percentage change in Lipitor global revenues from 2004 to 2008 (P <.001). Query preference for Lipitor over simvastatin was positively associated (r = 0.40) with a community's use of Medicare services. For every 1% increase in utilization of Medicare services in a community, there was a 0.2-unit increase in the ratio of Lipitor queries to simvastatin queries in that community (P = .02)., Conclusions: Specific search engine queries for medical information correlate with pharmaceutical revenue and with overall healthcare utilization in a community. This suggests that search query data can track community-wide characteristics in healthcare utilization and have the potential for informing payers and policy makers regarding trends in utilization.