TY - JOUR
T1 - Antinociceptive effect of calcitonin gene-related peptide in the central nucleus of amygdala
T2 - Activating opioid receptors through amygdala-periaqueductal gray pathway
AU - Xu, W.
AU - Lundeberg, T.
AU - Wang, Y. T.
AU - Li, Y.
AU - Yu, L. C.
N1 - Funding Information:
The study was supported by funds from the National Natural Science Foundation of China (NSFC) and the Karolinska Institute Foundation. We are very grateful to Mr. Ju-Shuai Zhang for generously supplying us with Fast Blue and to Miss Qingqing Han and Mr. Yun Zhao for the assistance in processing the microphotographs.
PY - 2003/6/6
Y1 - 2003/6/6
N2 - The central nucleus of amygdala (CeA) plays an important role in pain regulation. Calcitonin gene-related peptide (CGRP)-like immunoreactive fibers and CGRP receptors are distributed densely in CeA. The present study was performed to elucidate the role of CGRP in nociceptive regulation in the CeA of rats. Intra-CeA injection of CGRP induced dose-dependent increases in the hind-paw withdrawal latency tested by hotplate test and Randall Selitto Test, indicating an antinociceptive effect of CGRP in CeA. Furthermore, the antinociceptive effect of CGRP was blocked by intra-CeA administration of the CGRP receptor antagonist CGRP8-37, suggesting that CGRP receptor1 is involved in the CGRP-induced antinociception. The CGRP-induced antinociception was attenuated by s.c. injection of the opioid antagonist naloxone, suggesting an involvement of endogenous opioid systems in CGRP-induced antinociception. Moreover, it was demonstrated that opioid receptors in the periaqueductal gray, but not in CeA, contributed to the CGRP-induced antinociception, indicating the importance of the pathway between CeA and the periaqueductal gray in CGRP-induced antinociception. Combining retrograde fluorescent tracing with immunohistochemistry, we found that met-enkephalinergic neurons were innervated by CGRP-containing terminals in CeA. Furthermore, most neurons in the CeA retrogradely traced from the periaqueductal gray were contacted by CGRP-containing terminals and some of them were surrounded by characteristic basket-like structures formed by the terminals, suggesting that CGRP innervates the neurons which project from CeA to the periaqueductal gray. The results indicate that CGRP activates the met-enkephalinergic neurons, which project from CeA to the periaqueductal gray, producing antinociceptive effect in rats.
AB - The central nucleus of amygdala (CeA) plays an important role in pain regulation. Calcitonin gene-related peptide (CGRP)-like immunoreactive fibers and CGRP receptors are distributed densely in CeA. The present study was performed to elucidate the role of CGRP in nociceptive regulation in the CeA of rats. Intra-CeA injection of CGRP induced dose-dependent increases in the hind-paw withdrawal latency tested by hotplate test and Randall Selitto Test, indicating an antinociceptive effect of CGRP in CeA. Furthermore, the antinociceptive effect of CGRP was blocked by intra-CeA administration of the CGRP receptor antagonist CGRP8-37, suggesting that CGRP receptor1 is involved in the CGRP-induced antinociception. The CGRP-induced antinociception was attenuated by s.c. injection of the opioid antagonist naloxone, suggesting an involvement of endogenous opioid systems in CGRP-induced antinociception. Moreover, it was demonstrated that opioid receptors in the periaqueductal gray, but not in CeA, contributed to the CGRP-induced antinociception, indicating the importance of the pathway between CeA and the periaqueductal gray in CGRP-induced antinociception. Combining retrograde fluorescent tracing with immunohistochemistry, we found that met-enkephalinergic neurons were innervated by CGRP-containing terminals in CeA. Furthermore, most neurons in the CeA retrogradely traced from the periaqueductal gray were contacted by CGRP-containing terminals and some of them were surrounded by characteristic basket-like structures formed by the terminals, suggesting that CGRP innervates the neurons which project from CeA to the periaqueductal gray. The results indicate that CGRP activates the met-enkephalinergic neurons, which project from CeA to the periaqueductal gray, producing antinociceptive effect in rats.
KW - Calcitonin gene-related peptide
KW - Central nucleus of amygdala
KW - Hind-paw
KW - Opioid receptors
KW - Periaqueductal gray
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UR - http://www.scopus.com/inward/citedby.url?scp=0038404960&partnerID=8YFLogxK
U2 - 10.1016/S0306-4522(03)00069-1
DO - 10.1016/S0306-4522(03)00069-1
M3 - Article
C2 - 12732246
AN - SCOPUS:0038404960
SN - 0306-4522
VL - 118
SP - 1015
EP - 1022
JO - Neuroscience
JF - Neuroscience
IS - 4
ER -