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Biomedical subjects

Peter J Goadsby

Publications and source records attributed to Peter J Goadsby.

At least 19 recordsLinked to original sources
PubMed2003

Prostaglandin E2 injected into the posterior hypothalamus has no effect on trigeminal nociception in the rat.

Craniovascular prostaglandin E2 (PGE2) release is elevated in the headache phase of migraine and in experimental models of headache. PGE2 synthesised in the brain may be involved in modulating trigeminal nociception. We examined whether PGE2 injected into the posterior hypothalamus could modulate trigeminovascular nociception. In seven rats, electrophysiological recordings were made from trigeminal nucleus caudalis neurons responsive to noxious middle meningeal artery stimulation and inhibited by bicuculline activation of the posterior hypothalamus. Microinjection into the posterior hypothalamus of a non-pyrogenic dose of PGE2 (2.5 microg/ml) produced no effect on nociceptive trigeminal nucleus caudalis neurons compared with saline injection (P=0.29). The mean response to PGE2 injection was 97% of baseline. We conclude that PGE2 in the posterior hypothalamus is unlikely to play a significant role in modulating trigeminal nociception.

Animals↗
PubMed2003

Herbal medicine.

Explore the source record for details and available documents.

Humans↗
PubMed2003

Hypnic headache: clinical features, pathophysiology, and treatment.

Hypnic headache has been described in several case reports since 1981 and is regarded as an idiopathic headache disorder. In this review of 71 cases in the literature, the clinical features, neurophysiologic including polysomnographic findings, and treatment procedures are analyzed and the pathophysiology of this condition, which remains however speculative, is discussed. There is some evidence that hypnic headache is related to REM sleep. The analysis shows that hypnic headache most probably is an entity among the idiopathic headache disorders unassociated with structural lesions and does not belong to the trigeminal-autonomic cephalalgias. Lithium shows the best efficacy; indomethacin, flunarizine, and caffeine may also be useful.

Adult↗
PubMed2003

Trigeminal antinociception induced by bicuculline in the periaqueductal gray (PAG) is not affected by PAG P/Q-type calcium channel blockade in rat.

We have recently shown that injection of the P/Q-type (Ca(v)2.1/alpha(1A)) calcium channel blocker, omega-agatoxin IVA, into the periaqueductal gray (PAG) facilitates meningeal dural stimulation-evoked trigeminal nociceptive processing. We injected the GABA(A) antagonist bicuculline into the PAG in addition to the agatoxin and observed bicuculline's effect on neurons responding to dural stimulation recorded in the trigeminal nucleus caudalis of rats in order to determine if P/Q channel-mediated changes acted through GABAergic mechanisms. The inhibition of trigeminal nociceptive neurons characteristic of bicuculline administered into the PAG was maintained in the presence of blocked PAG P/Q-type calcium channels. This suggests the PAG descending pain modulatory pathway is not affected by P/Q-type calcium channel blockade at the postsynaptic GABAergic inhibitory interneuron and the facilitation produced by agatoxin is mediated by another mechanism. These findings have implications for disorders involving the PAG or P/Q-type channels, such as migraine, in particular for the development of preventative treatments, suggesting GABAergic and voltage-gated calcium channels could be separately modulated.

Animals↗
PubMed2003

The trigeminocervical complex and migraine: current concepts and synthesis.

Neurones in the trigeminocervical complex are the major relay neurones for nociceptive afferent input from the meninges and cervical structures; therefore, they are the neural substrates of head pain. This review highlights the importance of two basic mechanisms in headache physiology: convergence of nociceptive afferents and sensitization of trigeminocervical neurones. These physiologic findings have clinical correlates such as hypersensitivity and spread and referral of pain frequently seen in patients with primary headache, such as migraine. Special reference is made to the influence of structures from the upper cervical spine in generating and contributing to migraine headaches. The pathophysiology and functional relevance of these basic mechanisms to headaches is discussed in the context of recent experimental findings with regard to pain processing.

Calcium↗
PubMed2003

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing syndrome: a review.

The clinical features of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome have been reviewed in 50 patients reported in the English language literature. SUNCT syndrome is a rare condition that predominates slightly in men. The mean age at onset is 50 years. It is characterized by strictly unilateral attacks centered on the orbital or periorbital regions, forehead, and temple. Generally, the pain is severe and neuralgic in character. The usual duration ranges from 5 to 250 seconds, although the reported range of duration is 2 seconds to 20 minutes. Ipsilateral conjunctival injection and lacrimation are present in most, but not all patients. Most patients are thought to have no refractory periods and this has probably been unreported in the past. Episodic and chronic forms of SUNCT exist. The attack frequency varies from less than one attack daily to more than 60 attacks per hour. The attacks are predominantly diurnal, although frequent nocturnal attacks can occur in some patients. A functional magnetic resonance imaging study in SUNCT syndrome has demonstrated ipsilateral hypothalamic activation. SUNCT was thought to be highly refractory to treatment. However, recent open-label trials of lamotrigine, gabapentin, topiramate, and intravenous lidocaine have produced beneficial therapeutic responses. These results offer the promise of better treatments for this syndrome, but require validation in controlled trials.

Conjunctival Diseases↗
PubMed2003

Somatostatin infusion withdrawal: a study of patients with migraine, cluster headache and healthy volunteers.

Migraine and cluster headache are the most common disabling primary headache syndromes and are typically episodic. A reliable method of triggering such headache attacks facilitates the study and treatment of these disorders. There is sufficient clinical and laboratory evidence to suggest that somatostatin withdrawal may be a useful way of triggering headache. We studied 15 subjects, eight migraineurs, four cluster headache sufferers and three healthy controls. Each subject had a standard somatostatin infusion, 250 microg/h for 3.5h. Subjects were followed for 24h post-infusion. Growth hormone was suppressed in each subject demonstrating a biologically active infusion of somatostatin. None of the non-headache sufferers had pain. Seven of eight migraine sufferers had no immediate headache and no delayed headache. One migraineur experienced short lasting headache with no migrainous features. Three of four patients with cluster headache had no significant pain with the infusion, while one had pain after 1h. The results suggest that somatostatin infusion is not a reliable way to produce headache in experimental settings in either migraine or cluster headache. The data do not exclude a role for somatostatinergic mechanisms in primary headache.

Adult↗
PubMed2003

Does chronic daily headache arise de novo in association with regular use of analgesics?

BACKGROUND: The prevalence of chronic daily headache in association with regular use of analgesics is about 2%. Whether regular use of analgesics has a causal or consequential relationship to daily headache has not been established. A causal relationship has been suggested consequent to the observation of improvement or resolution of headache following analgesic withdrawal in patients attending headache clinics, but this observation has not been validated by controlled trials. PURPOSE: The aim of our investigation was to determine whether regular use of analgesics is associated with the development of chronic daily headache de novo and to characterize the clinical phenotype of those headaches by carefully studying chronic daily headache in patients with regular use of analgesics for a nonheadache indication. METHODS: Patients attending a rheumatology-monitoring clinic of second-line agents were interviewed by a training neurologist with regard to their analgesic and headache history. Headache classification was according to the criteria of the International Headache Society. Daily headache characteristics were surveyed via a standardized questionnaire, and headache features were further explored by a trained medical interviewer. RESULTS: Of 110 patients presenting to a rheumatology-monitoring clinic, 73% had a diagnosis of rheumatoid arthritis, 23% had seronegative arthritis, and 4% comprised a miscellaneous group. One hundred three were using one or more analgesics regularly for their arthritis. Of this group, 8 (7.6%) reported a history of chronic daily headache, each of whom reported a history of migraine. The onset of migraine occurred before the onset of chronic daily headache in 7 patients and at about the same time as the chronic daily headache in 1 patient. In those with onset of migraine prior to chronic daily headache, the mean interval before the onset of headache was 30 years (range, 10 to 50 years). Regular use of analgesics preceded the onset of daily headache in 5 patients by a mean of 5.4 years (range, 2 to 10 years). In 1 patient, analgesic use and the development of daily headache occurred at about the same time. In 1 patient, the onset of daily headache preceded regular use of analgesics by almost 30 years. Five of those with regular use of analgesics had been taking an opiate-based preparation in combination with a nonsteroidal anti-inflammatory agent in 4. Two had been on a combination of acetaminophen (paracetamol) and a nonsteroidal anti-inflammatory drug. The minimum number of tablets per week was 7, and the mean was 48 (range, 7 to 87). Of those patients who did not have daily headache, 41% had a history of migraine and 27% reported a history of tension-type headache. CONCLUSION: These findings suggest that individuals with primary headache, specifically migraine, are predisposed to developing chronic daily headache in association with regular use of analgesics.

Adult↗
PubMed2003

Management of trigeminal autonomic cephalgias and hemicrania continua.

The trigeminal autonomic cephalgias (TACs) are a group of primary headache disorders characterised by unilateral trigeminal distribution pain that occurs in association with ipsilateral cranial autonomic features. This group of headache disorders includes cluster headache, paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome). Although hemicrania continua has previously been classified amongst the TACs, its nosological status remains unclear. Despite their similarities, these disorders differ in their clinical manifestations and response to therapy, thus underpinning the importance of recognising them. We have outlined the clinical manifestations, differential diagnoses, diagnostic workup and the treatment options for each of these syndromes.

Analgesics↗
PubMed2002

The role of histamine in dural vessel dilation.

The pain of migraine is often throbbing suggesting an important role for the cranial blood vessels and their innervation by the trigeminal nerve. It is proposed that clinically effective anti-migraine compounds, such as 5-HT(1B/1D) agonists, have actions that include inhibiting calcitonin gene-related peptide (CGRP) release from trigeminal nerves. Human studies suggest that histamine can induce migraine possibly by activating nitric oxide (NO) synthase to promote endogenous NO production. The present studies investigated the effect of histamine and its antagonists on the cranial blood vessels using intravital microscopy to assess directly the diameter of dural arteries in sodium pentobarbitone anaesthetised rats. Electrical stimulation of a closed cranial window produces, by local depolarisation of nerves, dural vessel dilation that is monitored continuously on-line using video-microscopy and a video dimension analyser. Histamine infusion caused immediate and reproducible dilation of meningeal blood vessels (103.5+/-6%; n=40) that could be blocked by H(1)- (mepyramine) and H(2) (famotidine)-receptor antagonists (P<0.05), as well as a nitric oxide synthase inhibitor (N(G)-nitro-L-arginine methylester; P<0.05). Neurogenic dural vasodilation was not inhibited by H(2)-receptor antagonists, but was significantly inhibited by a H(1)-receptor antagonist at the high dose of 10 mg/kg. The present studies demonstrate that histamine is likely to activate NO synthase to promote NO production. There is also evidence that H(1)-receptors may be present on trigeminal neurones as the H(1)-receptor antagonist inhibited neurogenic vasodilation, albeit at a large dose.

Animals↗
PubMed2002

The effect of anti-migraine compounds on nitric oxide-induced dilation of dural meningeal vessels.

Migraine is characteristically accompanied by a throbbing quality of head pain thought to involve trigeminovascular afferents. Administration of nitric oxide (NO) donors provides the most reliable model of migraine induction in humans. The present studies used intravital microscopy to monitor the effect of local meningeal nerve stimulation and NO on dural blood vessels and any modulation of that effect by anti-migraine compounds. NO caused an immediate and reproducible dilation of meningeal blood vessels that was partially blocked by sumatriptan and indomethacin, while flunarizine and histamine H(1) and H(2) receptor antagonists were unable to block the dilation. Indomethacin also inhibited the neurogenic dilation while flunarizine did not. The present studies demonstrate that NO is unlikely to interact with histamine to produce its dilatory response. Sumatriptan and indomethacin inhibit the NO response by inhibiting trigeminal activation and calcitonin gene-related peptide (CGRP) release. Flunarizine does not modify either the neurogenic vasodilator response or the NO meningeal dilator response at least acutely.

Analgesics↗
PubMed2002

P/Q-type calcium-channel blockade in the periaqueductal gray facilitates trigeminal nociception: a functional genetic link for migraine?

The discovery of mis-sense mutations in the alpha1A subunit of the P/Q-type calcium channel in patients with familial hemiplegic migraine indicates the potential involvement of dysfunctional ion channels in migraine. The periaqueductal gray (PAG) region of the brainstem modulates craniovascular nociception and, through its role in the descending pain modulation system, may contribute to migraine pathophysiology. In this study we sought to investigate the possible link between the genetic mutations found in migraineurs and the PAG as a modulator of craniovascular nociception. We microinjected the P/Q-type calcium-channel blocker omega-agatoxin IVA into the rat ventrolateral PAG (vlPAG). We examined its effect on the nociceptive transmission of second-order neurons recorded in the trigeminal nucleus caudalis and activated by stimulation of the parietal dura mater. After injection of agatoxin into the vlPAG (n = 20) responses to dural stimulation were facilitated by 143% (p < 0.0001) for Adelta-fiber activity and 180% for C-fiber activity (p < 0.05). Similarly, spontaneous background activity increased by 163% (p < 0.0001). These results demonstrate that P/Q-type calcium channels in the PAG play a role in modulating trigeminal nociception and suggest a role for dysfunctional P/Q-type calcium channels in migraine pathophysiology.

Animals↗
PubMed2002

Pathophysiology of cluster headache: a trigeminal autonomic cephalgia.

Cluster headache is a form of primary neurovascular headache with the following features: severe unilateral, commonly retro-orbital, pain accompanied by restlessness or agitation, and cranial (parasympathetic) autonomic symptoms, such as lacrimation or conjunctival injection. It occurs in attacks typically of less than 3 h in length and in bouts (clusters) of a few months during which the patient has one or two attacks per day. The individual attack involves activation of the trigeminal-autonomic reflex; thus, such headaches can be broadly classified with the other trigeminal-autonomic cephalgias, such as paroxysmal hemicrania and the syndrome of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing. Observations of circadian biological changes and neuroendocrine disturbances have suggested a pivotal role for the hypothalamus in cluster headache. Functional neuroimaging with PET and anatomical imaging with voxel-based morphometry have identified the posterior hypothalamic grey matter as the key area for the basic defect in cluster headache.

Autonomic Nervous System Diseases↗