Differing central amine receptor sensitivity in different migraine subtypes? A neuroendocrine study using buspirone

Abstract

Despite the importance of the 5HT1A receptor in regulating central serotonergic tone, there is a dearth of research examining its role in migraine. In this study, we examined the hypothesis that there would be altered neuroendocrine responses to a 5HT1A agonist challenge in different migraine subtypes. Prolactin (PRL) responses to the 5HT1A receptor agonist drug buspirone were compared in 30 female subjects with migraine (ten migraine with aura, MA; ten migraine without aura, MO and ten chronic/transformed migraine, CM), and ten healthy controls matched for age, gender and menstrual status. None of the subjects were taking psychotropic medication or migraine prophylactic treatment and those with formal psychiatric disorder were excluded. Endocrine responses were determined by measuring differences between baseline PRL and maximum increases post-buspirone (deltaPRL). There was no difference in baseline PRL between groups. MA subjects did not differ in their PRL responses to buspirone compared to healthy controls. The MO group had a four-fold increase in mean deltaPRL responses compared to healthy controls. Mean deltaPRL was also increased in the CM group compared to controls, but the difference was less exaggerated. This study indicates that there is supersensitive central amine receptor function in MO and CM, but not in MA. These findings support the hypothesis that central 5HT function differs among the migraine subtypes. The results also suggest that migrainous 'transformation' may be associated with adaptive changes in central 5HT receptor sensitivity. The relative contribution of 'state' and 'trait' receptor function to these findings as well as the possible role of dopamine receptors is discussed.

Prolactin receptor in regulation of neuronal excitability and channels

“…[67][68][69][70][71] Strong evidence links these channels to mediating sensory neuronal activities by modulating the neuronal threshold of activation and efficiency of neurotransmission between sensory and spinal cord neurons. [72][73][74][75] A variety of pain conditions such as those associated with surgical procedures, 9,76 migraine, 11,34 burn, 30 rheumatoid arthritis, 26,27 and osteoarthritis 33 trigger an increase in serum PRL levels in men, and even more so in women. Recent evidence also suggests that inflammation, tissue injury and trauma lead to a sex-dependent up-regulation in extra-pituitary PRL in the vicinity of peripheral and central terminals of sensory neurons.…”

Ovarian Hormones and Migraine Headache: Understanding Mechanisms and Pathogenesis—Part 2

“…Cassidy et al 40 found a hypersensitivity of 5‐HT1A receptors during the early follicular phase (eg, first 5 days of the menstrual cycle). This hypersensitivity of 5‐HT1A receptors was reduced or absent in those with chronic migraine or menstrual status migrainosis 41,42 . D'Andrea et al 43 showed that platelet serotonin levels were highest during the mid‐cycle phase (late follicular and early luteal) and lowest during early follicular and late luteal time periods in migraine patients with and without aura.…”

Menstrual cycle-dependent febrile episode mediated by sequence-specific repression of poly(ADP-ribose) polymerase-1 on the transcription of the human serotonin receptor 1A gene

“…This study was the first to demonstrate the molecular mechanism underlying menstrual cycle‐dependent febrile episodes and implies that other cases with similar “febrile episodes” may also be a consequence of dysfunction of serotonin transmission caused by mutation(s) in one or more serotonergic genes. Because HTR1As play important roles in controlling serotonin homeostasis, it is not surprising that the three members of our patient's family who have the HTR1A ‐480delA mutation also have serotonin‐related disorders, such as migraines [Cassidy et al, 2003] and diabetes [Oxenkrug, 2010]. Furthermore, because the HTR1A ‐480delA mutation has been found in one case with schizophrenia [Kawanishi et al, 1998] and in the family reported here, this mutation may represent a mutation hot spot in HTR1A; thus, including it in molecular diagnosis for clinical screening of all serotonin‐related disorders could be useful.…”