Pain management research from the NIH HEAL Initiative.

This article presents an overview of the pain research programs within the National Institutes of Health (NIH) Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®. Launched in 2018 to address the opioid crisis, the NIH HEAL Initiative supports research on addiction prevention and treatment. A key component of addiction prevention is the development of new, effective, non-addictive treatments for acute and chronic pain. HEAL's innovate research portfolio spans the spectrum from therapeutic discovery and development through clinical trials and into clinical practice.

The Human Cost: Patient Contribution to Clinical Trials in Neurology.

Drug development abounds with corporate pharmaceutical capital investment and expenditure costs for new therapeutics. However, there is little data on the human investment, in particular, the number of participants required or the potential burden on and cost to individual trial participants so instrumental to this endeavor. Indeed, the human participant burden in clinical trials is poorly, if at all, described in the literature and we could identify no reports that have detailed the participant burden unique to neurology trials. The cost of clinical trials to participants, including the unique circumstances affecting enrollment of diverse participant populations, has only begun to be reflected in the wider clinical trial literature. Additionally, details of the indirect costs, including time commitment, out-of-pocket expenses, emotional expenditure, and potential loss of enrollment into a more successful trial by participants in trials that fail - the majority in the field - is also particularly striking in the lack of representation in the literature. Even in successful clinical trials, participants in the placebo group face both an emotional burden and medical risk of morbidity and mortality without potential offsetting therapeutic benefit.

Methodological approaches to botulinum toxin for the treatment of chronic pelvic pain, vaginismus, and vulvar pain disorders.

INTRODUCTION AND HYPOTHESIS: Botulinum toxin (BoNT) is increasingly used for pain, especially with muscle spasm. We describe our methodology for BoNT treatment of chronic pelvic pain (CPP) in women and place it in the context of the literature on techniques for this use. METHODS: Databases were searched using terms "botulinum toxin," "pelvic pain," and "vaginismus." Reports on vaginismus/vulvodynia/vestibulodynia (included if pelvic floor muscles were injected) were grouped as "vaginismus/vulvar pain disorders" (V/VPD). We analyzed the type of report, condition, toxin serotype/brand, dose/dilution, muscle selection, guidance technique, and anesthesia. Publications from the same authors without unique information were combined for specific analyses. RESULTS: Thirty-eight reports had analyzable information; many lacked complete information. Most were open-label prospective reports; there were four technical reports, one randomized comparison of doses and one placebo-controlled study of efficacy. Pelvic floor muscles were approached transvaginally, transperineally or transgluteally. BoNT brand/dose/dilution varied widely. Muscle localization techniques included anatomical landmarks only, electromyography, electrical stimulation with/without ultrasound, and fluoroscopy/CT scanning. Papers discussing analgesia utilized general anesthesia, conscious sedation with/without topical/local anesthesia, topical/local agent alone or pudendal block before or after injection. Cumulatively, 58-100% of patients with CPP and 71-100% of those with V/VPD improved. Serious adverse events (transient fecal incontinence/constipation, urinary incontinence/retention) were more frequent with higher doses. CONCLUSIONS: BoNT can be safely and tolerably injected into pelvic floor muscles in women as an out-patient procedure. This study identifies methodological factors to be considered in future studies and the critical need for high-quality clinical trials for this emerging treatment.

Muscle Selection for Focal Limb Dystonia.

Selection of muscles for botulinum toxin injection for limb dystonia is particularly challenging. Limb dystonias vary more widely in the pattern of dystonic movement and involved muscles than cervical dystonia or blepharospasm. The large variation in how healthy individuals perform skilled hand movements, the large number of muscles in the hand and forearm, and the presence of compensatory actions in patients with dystonia add to the complexity of choosing muscles for injection. In this article, we discuss approaches to selecting upper and lower extremity muscles for chemodenervation treatment of limb dystonia.

Botulinum Toxin Treatment of Blepharospasm, Orofacial/Oromandibular Dystonia, and Hemifacial Spasm.

Blepharospasm is a focal dystonia characterized by involuntary, repetitive eye closure. Orofacial and oromandibular dystonia describe involuntary dystonic movements of orofacial and oromandibular musculature. Hemifacial spasm is characterized by repetitive synchronous contraction of facial nerve innervated muscles on one side of the face. In this article, the clinical presentation, epidemiology, and approaches to treatment are reviewed. Technical aspects of using botulinum toxin for treatment and reported outcomes are discussed.

Botulinum toxin physiology in focal hand and cranial dystonia.

The safety and efficacy of botulinum toxin for the treatment of focal hand and cranial dystonias are well-established. Studies of these adult-onset focal dystonias reveal both shared features, such as the dystonic phenotype of muscle hyperactivity and overflow muscle contraction and divergent features, such as task specificity in focal hand dystonia which is not a common feature of cranial dystonia. The physiologic effects of botulinum toxin in these 2 disorders also show both similarities and differences. This paper compares and contrasts the physiology of focal hand and cranial dystonias and of botulinum toxin in the management of these disorders.

Migraine in women with chronic pelvic pain with and without endometriosis.

OBJECTIVE: To examine the prevalence of migraine in women with chronic pelvic pain with and without endometriosis. DESIGN: Prospective study of headache, pelvic pain, and quality of life before laparoscopic surgery for pelvic pain. Endometriosis was diagnosed pathologically. Headaches were classified as migraine or non-migraine using International Headache Society criteria. SETTING: Clinical research hospital. PATIENT(S): 108 women in a clinical trial for chronic pelvic pain (NCT00001848). INTERVENTION(S): Laparoscopy to diagnose endometriosis, assessment by neurologist to assess headaches. MAIN OUTCOME MEASURE(S): Prevalence of migraine and other headaches in women with chronic pelvic pain with or without endometriosis. Headache frequency, severity and relationship to pelvic pain and endometriosis. RESULT(S): Lifetime prevalence of definite or possible migraine was 67% of women with chronic pelvic pain. An additional 8% met criteria for possible migraine. Migraine was no more likely in women with endometriosis than those without. Women with the most severe headaches had a lower quality of life compared with those with pelvic pain alone. CONCLUSION(S): Migraine headache is common in women with chronic pelvic pain, regardless of endometriosis, and contributes to disability in those with both conditions. The strong association suggests a common pathophysiology.

Botulinum toxin treatment of occupational and focal hand dystonia.

Botulinum toxin is now the first-line therapy for writer's cramp and other occupational dystonias, with well-established efficacy and safety. Future studies will allow us to understand better the physiological effects of injection and to refine and enhance our treatment of focal hand dystonia.