Involvement of spinal somatostatin receptor SST(2A) in inflammation-induced thermal hyperalgesia: ultrastructural and behavioral studies in rats.
Our previous results have shown that somatostatin receptor subtype SST(2A) is responsible for thermal, but not mechanical nociceptive transmission in the rat spinal cord. The present study was undertaken to further examine the ultrastructural localization of SST(2A) receptor in lamina II of the spinal dorsal horn and the role of SST(2A) receptor in thermal hyperalgesia following Complete Freund's Adjuvant (CFA)-induced inflammation. We found that SST(2A) receptors in lamina II are located primarily in postsynaptic dendrites and soma, but not in axons or synaptic terminals. CFA-induced inflammation markedly increased SST(2A) receptor-like immunoreactivity in lamina II. Paw withdrawal latency (PWL) evoked by noxious heating was obviously shortened 1 h after intraplantar injection of CFA, exhibiting thermal hyperalgesia. Pre-blocking SST(2A) activity by intrathecal pre-administration of CYN154806, a broad-spectrum antagonist of SST(2) receptor, or specific antiserum against SST(2A) receptor (anti-SST(2A)) significantly attenuated thermal hyperalgesia in a dose-dependent fashion in CFA-treated rats. But, administration of anti-SST(2A) or CYN154806 after CFA treatment had no effect upon thermal hyperalgesia. Intrathecal application of SST(2A) agonist SOM-14 at different doses prior to CFA treatment did not influence thermal hyperalgesia in inflamed rats, but at a low dose shortened PWL evoked by noxious heating in normal rats. These results suggest that spinal SST(2A) receptors play a key role in triggering the generation, but not maintenance, of thermal hyperalgesia evoked by CFA-induced inflammation. The up-regulation of SST(2A) receptors in the spinal cord may be one of the mechanisms underlying inflammation-induced thermal hyperalgesia.
Zhao
Jun
J
Institute of Neurobiology, Institutes of Brain Science, Fu-Dan University, 138 Yixueyan Road, Shanghai 200032, People's Republic of China.
Hu
Jiang-Yuan
JY
Zhang
Yu-Qiu
YQ
Zhao
Zhi-Qi
ZQ
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000502:physiology*
C403089:CYN 154806; D009842:Oligopeptides; D017481:Receptors, Somatostatin; C106140:somatostatin receptor sst2A; D005620:Freund's Adjuvant