TY - JOUR
T1 - A neurohistochemical blueprint for pain-induced loss of appetite
AU - Malick, Amy
AU - Jakubowski, Moshe
AU - Elmquist, Joel K.
AU - Saper, Clifford B.
AU - Burstein, Rami
PY - 2001/8/14
Y1 - 2001/8/14
N2 - A common complaint among pain patients is that they lose their appetite. These accounts are anecdotal, however, and the neural mechanism underlying pain-induced loss of appetite remains unknown. In this study, we documented the occurrence of appetite loss in patients under migraine attack and investigated the neuronal substrate of pain-induced anorexia in our animal model of intracranial pain. We found that loss of appetite during the migraine attack in humans coincided strongly with the onset and duration of the head pain in 32/39 cases, and that brief noxious stimulation of the dura in conscious rats produced a transient suppression of food intake. Mapping of neuronal 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 dorsal horn areas that process nociceptive signals (laminae I, V) and in parabrachial and hypothalamic neurons positioned to suppress feeding behavior. In the parabrachial area, activated neurons were localized in the superior-lateral subnucleus, and 40% of them expressed the mRNA encoding the anorectic neuropeptide cholecystokinin. In the hypothalamus, activated Fos-positive neurons were found in the dorsomedial area of the ventromedial nucleus, and 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 hypothalamic neurons that normally inhibit appetite in response to metabolic cues is positioned to mediate the suppression of food intake by pain signals.
AB - A common complaint among pain patients is that they lose their appetite. These accounts are anecdotal, however, and the neural mechanism underlying pain-induced loss of appetite remains unknown. In this study, we documented the occurrence of appetite loss in patients under migraine attack and investigated the neuronal substrate of pain-induced anorexia in our animal model of intracranial pain. We found that loss of appetite during the migraine attack in humans coincided strongly with the onset and duration of the head pain in 32/39 cases, and that brief noxious stimulation of the dura in conscious rats produced a transient suppression of food intake. Mapping of neuronal 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 dorsal horn areas that process nociceptive signals (laminae I, V) and in parabrachial and hypothalamic neurons positioned to suppress feeding behavior. In the parabrachial area, activated neurons were localized in the superior-lateral subnucleus, and 40% of them expressed the mRNA encoding the anorectic neuropeptide cholecystokinin. In the hypothalamus, activated Fos-positive neurons were found in the dorsomedial area of the ventromedial nucleus, and 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 hypothalamic neurons that normally inhibit appetite in response to metabolic cues is positioned to mediate the suppression of food intake by pain signals.
UR - http://www.scopus.com/inward/record.url?scp=0035859958&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035859958&partnerID=8YFLogxK
U2 - 10.1073/pnas.171616898
DO - 10.1073/pnas.171616898
M3 - Article
C2 - 11504950
AN - SCOPUS:0035859958
SN - 0027-8424
VL - 98
SP - 9930
EP - 9935
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 17
ER -