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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that the serotonin (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) induced late occurring migraine-like headaches in a group of patients with eating disorders and controls (n = 52). In this report, we extend our analyses of these data and describe results indicating that headache responses following m-CPP are greater in patients with bulimia nervosa than controls, regardless of the presence of anorexia nervosa or major depression. Although patients with severe migraine-like headaches had higher peak m-CPP levels than patients without severe headaches, these levels are not higher than other groups studied who did not get headaches. These findings suggest that post-synaptic 5-HT receptor sensitivity is altered in the vascular tissues of bulimic patients. Additional disturbances in 5-HT function, perhaps presynaptic ones, may be associated with anorexia nervosa and major depression. Similar alterations in other 5-HT pathways at or above the level of the hypothalamus may contribute to binge eating and other behavioral symptoms of bulimia nervosa. Further studies exploring the functional integrity of 5-HT receptors and their subtypes are warranted in bulimic patients, as well as in patients with nonbulimic anorexia nervosa, minor and major depression without an eating disorder, and migraine and other headache patients.
Headache 1992 May
PMID:Headache responses following m-chlorophenylpiperazine in bulimics and controls. 162 57

In a study of serotonin (5-HT) function in patients with eating disorders and healthy control subjects, severe headaches with features of common migraine occurred unexpectedly in 28 of 52 subjects (54%) 8 to 12 hours after receiving a single oral dose of the 5-HT receptor agonist m-chlorophenylpiperazine (m-CPP), 0.5 mg/kg. None of the same subjects developed similar late-occurring headaches after placebo or the 5-HT precursor, L-tryptophan, 100 mg/kg given intravenously. The frequency of these migrainelike headaches was not significantly different between patients with bulimia or anorexia nervosa and control subjects, but incidence of headaches was significantly greater in subjects with a personal or family history of migraine, with almost all predisposed individuals (18 of 20, 90%) developing severe symptoms. Headache ratings were also significantly correlated (rho = 0.70; p less than 0.0001) with peak concentrations of m-CPP in plasma. These observations indicate that m-CPP may provide a novel probe for studies of the pathophysiology of migraine headaches.
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PMID:Induction of migrainelike headaches by the serotonin agonist m-chlorophenylpiperazine. 337 82

The neuroendocrine challenge paradigm provides a "window" on central neurotransmitter function in vivo. This strategy is based on the premise that the sensitivity of certain central receptors can be inferred from the magnitude of the hormonal response to specific pharmacologic probes. For example, the serotonin (5HT) receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin and induces migraine-like headaches. We have previously reported that the headache and cortisol responses to m-CPP are highly correlated, which may implicate a disturbance in central serotonergic neurotransmission in the pathogenesis of migraine. As pharmacologic probes with greater specificity for 5HT receptor subtypes become available, we may be able to elucidate these mechanisms with greater precision. The neuroendocrine challenge methodology is also applicable to the study of other neurotransmitter systems and other headache disorders.
Cephalalgia 1995
PMID:The neuroendocrine challenge paradigm in headache research. 758 26

The serotonin receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin, and induces migraine-like headaches. We have studied the neuroendocrine and headache responses to m-CPP in 8 subjects with migraine and 10 normal subjects. Each subject underwent two challenge tests, one with 0.25 mg/kg PO of m-CPP and the other with placebo, administered in a double-blind crossover format. Serial measurements of serum cortisol, prolactin, and m-CPP levels were made at 30-min intervals for 210 min following ingestion of the medication. The incidence and severity of headache was assessed by a structured telephone interview after each test. We confirmed that m-CPP stimulates the release of cortisol and prolactin, and may induce headache, in both migraine subjects and normal controls. The cortisol response as well as ratings of headache severity and duration directly correlated with plasma levels of m-CPP. There were highly significant associations between the cortisol response and both headache severity and duration, independent of m-CPP plasma levels. We did not find statistically significant differences between the migraine and normal subjects in terms of their neuroendocrine or headache responses to m-CPP.
Cephalalgia 1993 Dec
PMID:Headache and cortisol responses to m-chlorophenylpiperazine are highly correlated. 831 48

1. m-Chlorophenylpiperazine (m-CPP), a 5-HT1c-receptor agonist, induces migraine-like headaches when taken orally by migraine sufferers. The present study was undertaken to see what effects m-CPP had on 5-HT function in platelets. 2. Platelets from healthy male volunteers were loaded with [3H]-5-HT and continuously perfused in vitro with carboxygenated Krebs solution at 37 degrees C. After 30 min washout the effects of m-CPP, thrombin, 5-HT and ADP on the efflux of [3H]-5-HT were recorded. 3. m-CPP (0.5-500 microM) did not evoke an increase in the efflux of [3H]-5-HT over that occurring spontaneously whereas thrombin, unlabelled 5-HT and ADP did. The effects of 5-HT were potentiated by ADP. The results were identical whether or not the 5-HT reuptake blocker paroxetine (1 microM) was present. 4. m-CPP inhibited the increase in the efflux of [3H]-5-HT evoked by different concentrations of unlabelled 5-HT in the presence of ADP (2.5 microM) and displaced the 5-HT log concentration response curve to the right. A similar result was obtained with the 5-HT2-receptor antagonist ketanserin. 5. We conclude that m-CPP is a 5-HT2-receptor antagonist on human platelets, which is unlikely to account for its headache-inducing property, as many drugs effective in migraine prophylaxis have this action.
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PMID:The effects of 5-HT and m-chlorophenylpiperazine (m-CPP) on the efflux of [3H]-5-HT from human perfused platelets. 851 59

Serotonergic agonists such as m-chlorophenylpiperazine (m-CPP) and fenfluramine may induce migraine attacks. This has led to opposing theories concerning the role of 5-hydroxytryptamine (5HT) in triggering migraine attacks; is there hyperfunction or hypofunction of the central serotonergic system. Our review of the literature strongly suggests that m-CPP and fenfluramine provoke migraine attacks by stimulating, directly or indirectly, the 5HT2C/5HT2B receptors, although there is no total agreement with this interpretation. Central 5HT hypersensitivity in migraine patients, probably due to 5HT neuronal depletion, is proposed on the basis of review of electrophysiological tests and neuroendocrine challenge paradigms.
Cephalalgia 1997 Feb
PMID:Headache induced by serotonergic agonists--a key to the interpretation of migraine pathogenesis? 905 29

The central serotoninergic agonist m-chlorophenylpiperazine (m-CPP) stimulates several 5HT receptor subtypes. It induces the release of both cortisol and prolactin (PRL). In this study we investigated central serotoninergic responsiveness in cluster headache by monitoring cortisol and PRL responses to m-CPP administration. Twenty-three patients with episodic cluster headache and 17 sex-matched and age-matched healthy subjects were studied. The cluster headache patients were tested during a cluster period, and none were receiving prophylaxis. A single oral dose of m-CPP, 0.5 mg/kg, was given at time 0. Blood samples were drawn at -30, 0, 30, 60, 90, 120, 150 and 180 min. PRL and cortisol levels were assayed in the samples. PRL and cortisol delta maxima (delta maximum = maximum response - baseline level at time 0/baseline level at time 0) were evaluated in each patient and mean values compared. Serum levels of m-CPP were detected by HPLC and correlated to hormonal responses. Reduced cortisol (p < 0.02) and increased PRL (p < 0.05) delta maxima were observed in cluster headache patients. Increased basal cortisol plasma levels (p < 0.05) and reduced basal PRL plasma levels (p = 0.06) also characterized cluster headache patients. This is the first study evaluating central serotoninergic responsiveness to m-CPP in cluster headache and these data suggest impaired central serotoninergic function in this pathology.
Cephalalgia 1997 Oct
PMID:The m-chlorophenylpiperazine test in cluster headache: a study on central serotoninergic activity. 935 Mar 88

There are a few reports of side-effects of LHRHa treatment in childhood, the mechanisms of which remain little understood. Such effects can be local reactions: erythema, induration, wheal and sterile abscess formation, which can be possible causes of therapy failure. There are negative effects on growth velocity and final height requiring rhGH therapy or a suppressive treatment when bone age >13 years. Excessive weight gain can occur by various mechanisms: menopausal-like phenomena, or LHRHa influence on hypothalamic and/or leptin-mediated control of body weight. Other possible adverse effects involve increased ovarian volume with possible POS development; however, there is no evidence correlating LHRHa, hyperandrogenism and POS. The latter appears related to CPP onset with pre-existing hyperandrogenism, although lengthier follow-up is necessary to confirm this. Bone density decreases during therapy, but final peak bone mass is in the normal range. Frequent transitory side-effects include headaches, hot flushes, depression and irregular menses.
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PMID:Side effects of GnRH analogue treatment in childhood. 1096 24

Clinical and preclinical studies suggest that 5-HT and nitric oxide (NO) mobilization within the trigeminovascular system is fundamental to the initiation of migraine attacks., e.g. m-chlorophenylpiperazine (m-CPP) and glyceryl trinitrate (GTN) induce headache in humans. 5-HT2B receptors are known to mediate NO-dependent vasorelaxation in peripheral blood vessels, raising the possibility that this receptor is implicated in the pathogenesis of the disease. Therefore, we measured the effects of 5-HT2B agonists (m-CPP or BW723C86) or GTN on trigeminal nerves by quantifying Fos expression in the rat TNC. m-CPP (0.1 mg/kg, i.v.) induced time-dependent elevations in Fos-LI in the rat TNC 2 h and 8 h after injection. In contrast, neither intravenous GTN (0.5 microg/kg per min, infused 20 min) nor BW723C86 (0.1 mg/kg, i.v.) increased Fos-LI at 2 h or 8 h after administration. These data are not consistent with the involvement of the 5-HT2B/2C receptors or NO in trigeminovascular activation, and by inference migraine, and suggest the contribution of some other unidentified pathway.
Cephalalgia 2001 Feb
PMID:Investigations into migraine pathogenesis: time course for effects of m-CPP, BW723C86 or glyceryl trinitrate on appearance of Fos-like immunoreactivity in rat trigeminal nucleus caudalis (TNC). 1129 63

Background and objective Posttraumatic headache (PTH) is one of the most common, debilitating and difficult symptoms to manage after a mild traumatic brain injury, or concussion. However, the mechanisms underlying PTH remain elusive, in part due to the lack of a clinically relevant animal model. Here, we characterized for the first time, headache and pain-related behaviours in a rat model of concussion evoked by a mild closed head injury (mCHI) - the major type of military and civilian related trauma associated with PTH - and tested responses to current and novel headache therapies. Methods Concussion was induced in adult male rats using a weight-drop device. Characterization of headache and pain related behaviours included assessment of cutaneous tactile pain sensitivity, using von Frey monofilaments, and ongoing pain using the conditioned place preference or aversion (CPP/CPA) paradigms. Sensitivity to headache/migraine triggers was tested by exposing rats to low-dose glyceryl trinitrate (GTN). Treatments included acute systemic administration of sumatriptan and chronic systemic administration of a mouse anti-CGRP monoclonal antibody. Results Concussed rats developed cephalic tactile pain hypersensitivity that was resolved by two weeks post-injury and was ameliorated by treatment with sumatriptan or anti-CGRP monoclonal antibody. Sumatriptan also produced CPP seven days post mCHI, but not in sham animals. Following the resolution of the concussion-evoked cephalic hypersensitivity, administration of GTN produced a renewed and pronounced cephalic pain hypersensitivity that was inhibited by sumatriptan or anti-CGRP antibody treatment as well as a CGRP-dependent CPA. GTN had no effect in sham animals. Conclusions Concussion leads to the development of headache and pain-related behaviours, in particular sustained enhanced responses to GTN, that are mediated through a CGRP-dependent mechanism. Treatment with anti-CGRP antibodies may be a useful approach to treat PTH.
Cephalalgia 2018 02
PMID:Development of CGRP-dependent pain and headache related behaviours in a rat model of concussion: Implications for mechanisms of post-traumatic headache. 2789 34


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