Objective.-To determine the effect of botulinum toxin type A on calcitonin gene-related peptide secretion from cultured trigeminal ganglia neurons.Background.-The ability of botulinum toxins to cause muscle paralysis by blocking acetylcholine release at the neuromuscular junction is well known. Previous studies and clinical observations have failed to demonstrate sensory changes related to botulinum toxins or the disease of botulism. Recent studies, however, have suggested that botulinum toxin type A injected into pericranial muscles may have a prophylactic benefit in migraine. This observation has renewed the debate of a mechanism of sensory inhibition mediated by botulinum toxin type A.Methods.-Primary cultures of rat trigeminal ganglia were utilized to determine whether botulinum toxin type A could directly decrease the release of calcitonin gene-related peptide, a neuropeptide involved in the underlying pathophysiology of migraine. Untreated cultures or cultures stimulated with a depolarizing stimulus (potassium chloride) or capsaicin, an agent known to activate sensory C fibers, were treated for 3, 6, or 24 hours with clinically effective doses of botulinum toxin type A or a control vehicle. The amount of calcitonin gene-related peptide secreted into the culture media following the various treatments was determined using a specific radioimmunoassay.Results. Conclusions.-These data provide the first evidence that botulinum toxin type A can directly decrease the amount of calcitonin gene-related peptide released from trigeminal neurons. The results suggest that the effectiveness of botulinum toxin type A in the treatment of migraine may be due, in part, to its ability to repress calcitonin gene-related peptide release from activated sensory neurons.

BackgroundCalcitonin gene-related peptide (CGRP), a neuropeptide released from trigeminal nerves, is implicated in the underlying pathology of temporomandibular joint disorder (TMD). Elevated levels of CGRP in the joint capsule correlate with inflammation and pain. CGRP mediates neurogenic inflammation in peripheral tissues by increasing blood flow, recruiting immune cells, and activating sensory neurons. The goal of this study was to investigate the capability of CGRP to promote peripheral and central sensitization in a model of TMD.ResultsTemporal changes in protein expression in trigeminal ganglia and spinal trigeminal nucleus were determined by immunohistochemistry following injection of CGRP in the temporomandibular joint (TMJ) capsule of male Sprague-Dawley rats. CGRP stimulated expression of the active forms of the MAP kinases p38 and ERK, and PKA in trigeminal ganglia at 2 and 24 hours. CGRP also caused a sustained increase in the expression of c-Fos neurons in the spinal trigeminal nucleus. In contrast, levels of P2X3 in spinal neurons were only significantly elevated at 2 hours in response to CGRP. In addition, CGRP stimulated expression of GFAP in astrocytes and OX-42 in microglia at 2 and 24 hours post injection.ConclusionsOur results demonstrate that an elevated level of CGRP in the joint, which is associated with TMD, stimulate neuronal and glial expression of proteins implicated in the development of peripheral and central sensitization. Based on our findings, we propose that inhibition of CGRP-mediated activation of trigeminal neurons and glial cells with selective non-peptide CGRP receptor antagonists would be beneficial in the treatment of TMD.

Naratriptan 2.5 mg appears to prevent migraine headache when given early in prodrome. If headache occurs, severity appears to be reduced.

Neurology. 2002;58(9 suppl 6):S27‐S31. Migraine is a heterogeneous condition that causes symptoms that vary both among individuals and within individuals from attack to attack. We examined and reviewed several important lessons on the diagnosis of migraine learned from the distribution of headache types and patterns of treatment response in the Spectrum Study, including recruitment and diagnostic issues. The accuracy of an initial diagnosis, assigned by a clinician in the context of a clinical trial, was compared with the results of a final diagnosis, assigned by a neurologist, reviewing the initial evaluation as well as headache diaries for up to 10 attacks. Several lessons can be learned from the Spectrum Study. Recruitment difficulties teach us that disabling tension‐type headache is difficult to find, suggesting that it is rare. Examination of the final diagnosis given after diary evaluations suggests that a diagnosis of migraine can usually be confirmed for patients with disabling headache. After reclassification of the final sample of 432 subjects, 24/75 (32%) patients initially clinically classified as having disabling episodic tension‐type headache proved to have migraine or migrainous headache after a diary review. Among study participants, 90% of subjects with disabling headache (HIMQ score>250) had a migraine‐related disorder. Treatment response suggests that, in migraineurs, tension‐type headaches may have a pathophysiology similar to that of migraine. The diary data show that mild headaches in migraine often evolve into full‐blown migraine. The Spectrum Study supports the view that, for patients with disabling episodic headache, migraine is often the correct diagnosis. In clinical practice, the suspicion of migraine should be high for patients experiencing episodic disabling headache. Assessment of headache‐related disability may assist practitioners in making a diagnosis of migraine. Comment: The Spectrum Study (Lipton R, et al. Headache. 2000;40:783‐791) has proven to be one of the most important investigations to be reported in the modern clinical headache literature. The results, if accepted, constitute a shift in paradigm for the diagnosis of migraine, or, rather, a return to Neil Raskin's concept of the “continuum of benign recurring headache.” One conclusion of the study was that all headaches in patients with coexisting episodic tension‐type headache, migrainous headache, and migraine behaved the same in their response to sumatriptan. This suggests that the three headache types might all be manifestations of the same primary headache disorder, namely migraine, rather than representing three independent disorders, as currently suggested by the IHS classification system. Another finding of the Spectrum Study was that diary review often changed the diagnosis of headaches initially thought to be tension‐type to migraine, suggesting both that longitudinal data can be illuminating with respect to diagnosis, and that, as Richard Lipton notes, “for patients with disabling episodic headache, migrain...

Background.-This study aims to determine if repetitive sphenopalatine ganglion (SPG) blockades with 0.5% bupivacaine delivered with the Tx360 ® device results in long-term improvement in chronic migraine (CM). The SPG is a small concentrated structure of neuronal tissue that resides within the pterygopalatine fossa in close proximity to the sphenopalatine foramen and is innervated by the maxillary division of the trigeminal nerve. In a previous article, these authors reported repetitive SPG blockades with 0.5% bupivacaine delivered by the Tx360 ® device, which was an effective and well-tolerated intervention to incrementally decrease baseline headache intensity of subjects with CM.Methods.-This was a double-blind, parallel-arm, placebo-controlled, randomized pilot study using a novel intervention for acute treatment in CM. A total of 41 subjects were enrolled at two headache specialty clinics in the USA. Eligible subjects were between 18 and 80 years of age and had a history of CM defined by International Classification of Headache Disorders-II definition. Subjects were allowed a stable dose of migraine preventive medications that was maintained throughout the study.