A neurohistochemical blueprint for pain-induced loss of appetite

A common complaint among pain patients is that they lose their appetite. Th ese accounts are anecdotal, however, and the neural mechanism underlying pa in-induced loss of appetite remains unknown. In this study, we documented t he occurrence of appetite loss in patients under migraine attack and invest igated the neuronal substrate of pain-induced anorexia in our animal model of intracranial pain. We found that loss of appetite during the migraine at tack in humans coincided strongly with the onset and duration of the head p ain in 32/39 cases, and that brief noxious stimulation of the dura in consc ious rats produced a transient suppression of food intake. Mapping of neuro nal activation in the rat showed that noxious dural stimulation induced a 3 - to 4-fold increase in the number of Fos-positive neurons in medullary dor sal horn areas that process nociceptive signals (laminae I, V) and in parab rachial and hypothalamic neurons positioned to suppress feeding behavior. I n the parabrachial area, activated neurons were localized in the superior-l ateral subnucleus, and 40% of them expressed the mRNA encoding the anorecti c neuropeptide cholecystokinin. in the hypothalamus, activated Fos-positive neurons were found in the dorsomedial area of the ventromedial nucleus, an d 76% of them expressed the mRNA for cholecystokinin type-B receptor. Based on these findings, we suggest that at least one of several groups of hypot halamic neurons that normally inhibit appetite in response to metabolic cue s is positioned to mediate the suppression of food intake by pain signals.