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Biomedical subjects

P J Goadsby

Publications and source records attributed to P J Goadsby.

At least 19 recordsLinked to original sources
PubMed2007

Serotonin receptor ligands: treatments of acute migraine and cluster headache.

Fuelled by the development of the serotonin 5-HT(1B/1D) receptor agonists, the triptans, the last 15 years has seen an explosion of interest in the treatment of acute migraine and cluster headache. Sumatriptan was the first of these agonists, and it launched a wave of therapeutic advances. These medicines are effective and safe. Triptans were developed as cranial vasoconstrictors to mimic the desirable effects of serotonin, while avoiding its side-effects. It has subsequently been shown that the triptans' major action is neuronal, with both peripheral and central trigeminal inhibitory effects, as well as actions in the thalamus and at central modulatory sites, such as the periaqueductal grey matter. Further refinements may be possible as the 5-HT(1D) and 5-HT(1F) receptor agonists are explored. Serotonin receptor pharmacology has contributed much to the better management of patients with primary headache disorders.

Acute Disease↗
PubMed2007

Almotriptan and zolmitriptan in the acute treatment of migraine.

OBJECTIVE: To compare almotriptan and zolmitriptan in the treatment of acute migraine. METHODS: This multicentre, double-blind trial randomized adult migraineurs to almotriptan 12.5 mg (n = 532) or zolmitriptan 2.5 mg (n = 530) for the treatment of a single migraine attack. The primary end point was sustained pain free plus no adverse events (SNAE); other end points included pain relief and pain free at several time points, sustained pain free, headache recurrence, use of rescue medication, functional impairment, time lost because of migraine, treatment acceptability, and overall treatment satisfaction. RESULTS: No significant difference was seen in SNAE (almotriptan 29.2% vs zolmitriptan 31.8%) or the other efficacy end points measured. The incidence of triptan-associated AEs and triptan-associated central nervous system AEs was significantly lower for patients receiving almotriptan compared to zolmitriptan. CONCLUSIONS: Almotriptan and zolmitriptan were associated with similar efficacy and overall tolerability in the treatment of acute migraine. Almotriptan was associated with a significantly lower rate of triptan-associated AEs.

Acute Disease↗
PubMed2007

Paroxysmal hemicrania responding to topiramate.

Chronic paroxysmal hemicrania (CPH) is a rare primary headache syndrome, which is classified along with cluster headache and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) as a trigeminal autonomic cephalalgia. CPH is exquisitely responsive to indomethacin so much so that the response is one of the current diagnostic criteria. The case of a patient with CPH, who had marked epigastric symptoms with indomethacin treatment and responded well to topiramate 150 mg daily, is reported. Cessation of topiramate caused return of episodes, and the response has persisted for 2 years. Topiramate may be a treatment option in CPH.

Adult↗
PubMed2006

Medication-overuse headache in patients with cluster headache.

OBJECTIVE: Medication-overuse headache (MOH) in cluster headache (CH) patients is incompletely described, perhaps because of the relatively low prevalence of CH. METHODS: The authors describe a retrospective series of 17 patients (13 men, 4 women) with CH who developed MOH in association with overuse of a wide range of monotherapies or varying combinations of simple analgesics (n = 9), caffeine (n = 1), opioids (n = 10), ergotamine (n = 3), and triptans (n = 14). The series includes both episodic (n = 7) and chronic (n = 10) CH patients. RESULTS: A specific triptan-overuse headache diagnosis was made in 3 patients, an opioid-overuse headache diagnosis was made in 1 patient, and an ergotamine-overuse headache diagnosis was made in 1 patient. In approximately half of the patients (n = 8), the MOH phenotype was a bilateral, dull, and featureless daily headache. In the other 9 patients, the MOH was characterized by at least one associated feature, most commonly nausea (n = 6), exacerbation with head movement (n = 5), or throbbing character of the pain (n = 5). The common denominator in 15 patients was a personal or family history, or both, of migraine. The 2 other patients gave a family history of unspecified headaches. Medication withdrawal was attempted and successful in 13 patients. CONCLUSIONS: Medication-overuse headache is a previously underrecognized and treatable problem associated with cluster headache (CH). CH patients should be carefully monitored, especially those with a personal or family history of migraine.

Adult↗
PubMed2006

Occipital afferent activation of second order neurons in the trigeminocervical complex in rat.

Stimulation of the greater occipital nerve produces excitation of second order neurons in the trigeminocervical complex. Given that neck pain is very common in primary headache disorders, this convergent excitation may play a role in pain referral from cervical structures. While previous studies have demonstrated a physiological model for this convergence, this study sought an anatomical approach to examine the distribution of second order neurons in the trigeminocervical complex receiving greater occipital nerve input. In addition, the role of glutamatergic NMDA receptor activation within the trigeminocervical complex in response to cervical afferents was studied. Noxious stimulation of the occipital muscle in rat using mustard oil and mineral oil produced significantly altered Fos expression in the trigeminocervical complex compared with the surgical control (H(4)=31.3, P<0.001, Kruskal-Wallis). Baseline expression was 11 (median, range 4, 17) fos positive cells in the trigeminocervical complex, occipital muscle treated with mustard oil produced 23 (17, 33) and mineral oil a smaller effect of 19 (15, 25) fos positive cells, respectively (P=0.046). The effects of both mustard and mineral oil were reversed by the NMDA-receptor antagonist MK801. This study introduces a model for examining trigeminocervical complex activity after occipital afferent stimulation in the rat that has good anatomical resolution and demonstrates involvement of glutamatergic NMDA receptors at this important synapse.

Afferent Pathways↗
PubMed2006

Greater occipital nerve injection in primary headache syndromes--prolonged effects from a single injection.

Most patients with primary headache syndromes who have frequent attacks of pain have tenderness in the sub-occipital region. Injection of the greater occipital nerve (GON) with local anesthetic and corticosteroids has been widely used in clinical practice for many years, yet there is no clear understanding of its mechanisms of action. Moreover, there is no current gold-standard of practice regarding GON injections in the management of headache. We audited of our practice to generate hypotheses about the range of primary headaches that might benefit, to determine response rates to power future studies, and to assess whether we should continue to do this procedure. Twenty-six of fifty-seven injections in 54 migraineurs yielded a complete or partial response that lasted for the partial response a median of 30 days. For cluster headache 13 of 22 injections yielded a complete or partial response lasting for a median of 21 days for the partial response. Tenderness over the GON was strongly predictive of outcome, although local anesthesia after the injection was not. The presence or absence of medication overuse did not predict outcome. Apart from two patients with a small patch of alopecia the injection was well tolerated. GON injection is a useful tool in some patients that provides interim relief while other approaches are explored. It is remarkable that in all conditions in which an effect is observed the response time so much exceeds the local anesthetic effect that the mechanism of action may well be through changes in brain nociceptive pathways.

Afferent Pathways↗
PubMed2006

Animal models of migraine: looking at the component parts of a complex disorder.

Animal models of human disease have been extremely helpful both in advancing the understanding of brain disorders and in developing new therapeutic approaches. Models for studying headache mechanisms, particularly those directed at migraine, have been developed and exploited efficiently in the last decade, leading to better understanding of the potential mechanisms of the disorder and of the action for antimigraine treatments. Model systems employed have focused on the pain-producing cranial structures, the large vessels and dura mater, in order to provide reproducible physiological measures that could be subject to pharmacological exploration. A wide range of methods using both in vivo and in vitro approaches are now employed; these range from manipulation of the mouse genome in order to produce animals with human disease-producing mutations, through sensitive immunohistochemical methods to vascular, neurovascular and electrophysiological studies. No one model system in experimental animals can explain all the features of migraine; however, the systems available have begun to offer ways to dissect migraine's component parts to allow a better understanding of the problem and the development of new treatment strategies.

Animals↗
PubMed2006

Modulation of nociceptive dural input to the trigeminal nucleus caudalis via activation of the orexin 1 receptor in the rat.

Migraine pathophysiology is thought to involve the trigeminal innervation of the dura mater and intracranial blood vessels. Electrical stimulation of dural blood vessels is painful in humans and causes activation of neurons in the caudal-most portion of the trigeminal nucleus in experimental animals. The hypothalamic neuropeptides orexin A and B are selectively synthesized in the lateral and posterior hypothalamus, and recent findings have implicated their involvement in nociceptive processing. To evaluate the potential for orexin receptor modulation of trigeminovascular nociceptive afferents, we examined the effects of intravenous orexin A and B on responses of neurons in the trigeminal nucleus caudalis. To dissect the receptor pharmacology of responses to stimulation we utilized the novel orexin 1 receptor (OX(1)R) antagonist N-(2-methyl-6-benzoxazolyl)-N''-1,5-naphthyridin-4-yl urea (SB-334867). Orexin A 30 microg/kg (F(1.9,9.8) = 21.93, P < 0.001) and 50 microg/kg (F(3.2,16.4) = 3.28, P < 0.045) inhibited the A-fibre responses to dural electrical stimulation over 60 min. Maximum inhibition was achieved at 25 min for both 30 microg/kg (t(5) = 19.83, n = 6, P < 0.001) and 50 microg/kg (t(5) = 7.74, n = 6, P < 0.001). The response with orexin A 30 microg/kg was reversed by pretreatment with the OX(1)R antagonist SB-334867 (F(3.5,17.5) = 0.49, P = 0.73), which had no effect when given alone. Orexin B and control vehicle administration had no significant effect on trigeminal neuronal firing. The current study demonstrates that orexin A is able to inhibit A-fibre responses to dural electrical stimulation via activation of the OX(1)R.

Action Potentials↗
PubMed2006

The relationship between neuropeptide Y expression and headache in pituitary tumours.

Patients with pituitary tumours often present with disabling headache but there is no clear relationship between tumour size and headache. Neuropeptide Y (NPY) has been identified in pituitary tumours and may serve as a biochemical marker of the propensity for headache. Using immunohistochemical techniques we examined 27 consecutive pituitary adenoma specimens for NPY (including one normal postmortem control anterior pituitary specimen). A separate observer divided the patients into two groups: headache and non-headache. The association between the presence of NPY and headache was tested. NPY positive immunoreactivity was seen in 13 tumour specimens (50%, 13 of 26 pituitary tumour specimens), characterized by cytoplasmic and nuclear staining patterns. There was no significant association between the presence of NPY and headache (chi(2) = 0.9, P = 0.34). We did not observe NPY in the normal anterior pituitary control specimen. NPY was present in four of five (80%) growth hormone-secreting tumours and two of two (100%) prolactinomas, compared with four of 11 (36%) non-functioning adenomas. The mechanism of many pituitary tumour-associated headaches remains undetermined. The significance of NPY positivity in pituitary tumours is unknown, although the results of this study may implicate this peptide in the control of somatotroph and lactotroph activity. Our data do not support a clear role for NPY pituitary tumour-associated headache.

Chi-Square Distribution↗
PubMed2006

EFNS guideline on the drug treatment of migraine - report of an EFNS task force.

Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients' quality of life. To give evidence-based or expert recommendations for the different drug treatment procedures of the different migraine syndromes based on a literature search and an consensus in an expert panel. All available medical reference systems were screened for all kinds of clinical studies on migraine with and without aura and on migraine-like syndromes. The findings in these studies were evaluated according to the recommendations of the EFNS resulting in level A,B, or C recommendations and good practice points. For the acute treatment of migraine attacks, oral non-steroidal anti-inflammatory drugs (NSAIDs) and triptans are recommended. The administration should follow the concept of stratified treatment. Before intake of NSAIDs and triptans, oral metoclopramide or domperidon is recommended. In very severe attacks, intravenous acetylsalicylic acid or subcutaneous sumatriptan are drugs of first choice. A status migrainosus can probably be treated by steroids. For the prophylaxis of migraine, betablockers (propranolol and metoprolol), flunarizine, valproic acid, and topiramate are drugs of first choice. Drugs of second choice for migraine prophylaxis are amitriptyline, naproxen, petasites, and bisoprolol.

Advisory Committees↗
PubMed2006

Increased urinary excretion of nitric oxide metabolites in longitudinally monitored migraine patients.

This study evaluated a relationship between nitric oxide (NO) and migraine attacks in order to gain insight into migraine pathomechanism. The study groups consisted of 12 migraineurs and eight controls. All subjects collected morning urine samples for 40 consecutive days. Urinary NO metabolites, nitrite/nitrate (NO(x)) levels were measured with the vanadium-based assay, whilst creatinine (Cr) and neopterin were determined with high-performance liquid chromatography. The mean urinary NO(x)/Cr ratio and number of NO(x) peaks was significantly greater in the migraine group compared with controls (P = 0.01 and P = 0.007, respectively). In the second approach, high NO(x) values were re-assessed in relation to raised neopterin, a marker of systemic infection or inflammation, and were excluded. The excretion of NO(x) persisted being pulsatile, and migraineurs had more peaks compared with controls (P = 0.01). In seven patients, NO(x) peaks coincided with headache days. This was more frequent than expected by random association in four patients (Monte-Carlo simulation; odds ratios: 2.16-7.77; no overlap of 95% CI). In four patients, NO(x) peaks preceded or followed headache days. Although there is a difference in the pattern of urinary NO(x) excretion between control and migraine populations, the variable temporal association of NO(x) peaks and headaches suggests a complex role of NO in this condition.

Biomarkers↗
PubMed2006

EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias.

Cluster headache and the other trigeminal-autonomic cephalalgias [paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome] are rare but very disabling conditions with a major impact on the patient's quality of life. The objective of this study was to give evidence-based recommendations for the treatment of these headache disorders based on a literature search and consensus amongst a panel of experts. All available medical reference systems were screened for any kind of studies on cluster headache, paroxysmal hemicrania and SUNCT syndrome. The findings in these studies were evaluated according to the recommendations of the European Federation of Neurological Societies resulting in level A, B or C recommendations and good practice points. For the acute treatment of cluster headache attacks, oxygen (100%) with a flow of at least 7 l/min over 15 min and 6 mg subcutaneous sumatriptan are drugs of first choice. Prophylaxis of cluster headache should be performed with verapamil at a daily dose of at least 240 mg (maximum dose depends on efficacy or tolerability). Although no class I or II trials are available, steroids are clearly effective in cluster headache. Therefore, the use of at least 100 mg methylprednisone (or equivalent corticosteroid) given orally or at up to 500 mg i.v. per day over 5 days (then tapering down) is recommended. Methysergide, lithium and topiramate are recommended as alternative treatments. Surgical procedures, although in part promising, require further scientific evaluation. For paroxysmal hemicranias, indomethacin at a daily dose of up to 225 mg is the drug of choice. For treatment of SUNCT syndrome, large series suggest that lamotrigine is the most effective preventive agent, with topiramate and gabapentin also being useful. Intravenous lidocaine may also be helpful as an acute therapy when patients are extremely distressed and disabled by frequent attacks.

Advisory Committees↗
PubMed2006

Paroxysmal hemicrania in a family.

Paroxysmal hemicrania (PH) is a trigeminal autonomic cephalgia, characterised by unilateral attacks responsive to indomethacin. There are no published reports of a family history in PH. We report a mother and daughter both with PH. The daughter and her sister also had migraine.

Adult↗
PubMed2006

Abnormal blink reflex studies in a patient with supraorbital neuralgia.

A 44-year-old female with gabapentin-responsive supraorbital neuralgia is presented. She had pre- and post-treatment nociceptive-specific blink reflexes carried out which tracked the good clinical outcome from treatment. The results of the electrophysiological testing imply some central component to the pathophysiology of supra-orbital neuralgia.

Adult↗
PubMed2006

New appendix criteria open for a broader concept of chronic migraine.

After the introduction of chronic migraine and medication overuse headache as diagnostic entities in The International Classification of Headache Disorders, Second Edition, ICHD-2, it has been shown that very few patients fit into the diagnostic criteria for chronic migraine (CM). The system of being able to use CM and the medication overuse headache (MOH) diagnosis only after discontinuation of overuse has proven highly unpractical and new data have suggested a much more liberal use of these diagnoses. The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for CM and MOH presented in this paper. These criteria are included in the appendix of ICHD-2 and are meant primarily for further scientific evaluation but may be used already now for inclusion into drug trials, etc. It is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously, i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than one substance. If these new criteria for CM and MOH prove useful in future testing, the plan is to include them in a future revised version of ICHD-2.

Chronic Disease↗
PubMed2006

Intravital microscopy on a closed cranial window in mice: a model to study trigeminovascular mechanisms involved in migraine.

The purpose of the study was to develop a mouse model to study trigeminovascular mechanisms using intravital microscopy on a closed cranial window. In addition, we studied exogenous and endogenous calcitonin gene-related peptide (CGRP)-mediated vasodilation in dural arteries. Arteries in C57BL/6Jico mice were constricted with endothelin-1, which reduced the baseline diameter by 65-75%. Subsequently, vasodilation was induced by alpha-CGRP, capsaicin or transcranial electrical stimulation of perivascular trigeminal nerves in the absence or presence of different concentrations of BIBN4096BS or sumatriptan. Both alpha-CGRP and capsaicin induced vasodilation in preconstricted arteries. Transcranial electrical stimulation also induced current-dependent relaxation of dural arteries with 100 microA producing maximal dilation in the control group. BIBN4096BS blocked the responses evoked by alpha-CGRP and capsaicin, as well as electrical stimulation, whereas sumatriptan attenuated only vasodilation induced by electrical stimulation. This model is likely to prove useful in dissecting elements of the trigeminovascular system and for exploring pathophysiological aspects of migraine, especially in future studies using transgenic mice with mutations relevant to those observed in patients with migraine.

Animals↗
PubMed2006

Triptans in orgasmic headache.

Orgasmic headache (headache associated with sexual activity type 2 according to the International Headache Society classification) is a sudden severe headache which occurs at orgasm. Experiences with triptan therapy are described. Two out of four patients with severe headache continuing for >2 h had a positive response to acute triptan therapy. Two out of three patients using triptans as short-term prophylaxis reported a reliable response on several occasions. Triptans might be a treatment option to shorten orgasmic headache attacks after the diagnosis is clear and, particularly, subarachnoid haemorrhage has been excluded. In patients who chose to predict their sexual activity, short-term prophylaxis with oral triptans 30 min before sexual activity might be a therapeutic option in those not responsive to or not tolerating indomethacin.

Adult↗