Differential inhibitory effects of mu-opioids on substance P- and capsaicin-induced nociceptive behavior in mice.
The antinociceptive mechanisms of the selective mu-opioid receptor agonists [D-Ala2,NMePhe4,Gly(ol)5]enkephalin (DAMGO), H-Tyr-D-Arg-Phe-beta-Ala-OH (TAPA) or H-Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA-NH2) against substance P (SP)- or capsaicin-elicited nociceptive behaviors was investigated in mice. DAMGO, TAPA or TAPA-NH2 given intrathecally inhibited the nociceptive behaviors elicited by intrathecally administered SP or capsaicin, and these antinociceptive effects were completely eliminated by intrathecal co-administration with D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective mu-opioid receptor antagonist. Pretreatment subcutaneously with naloxonazine, a selective mu1-opioid receptor antagonist, partially attenuated the antinociceptive effect of TAPA-NH2, but not DAMGO and TAPA, against SP. However, the antinociception induced by TAPA, but not DAMGO and TAPA-NH2, against capsaicin was significantly inhibited by naloxonazine. On the other hand, co-administration intrathecally with Tyr-D-Pro-Trp-Gly-NH2 (D-Pro2-Tyr-W-MIF-1), a selective mu2-opioid receptor antagonist, significantly attenuated the antinociceptive effects of DAMGO, but not TAPA and TAPA-NH2, against capsaicin, while the antinociceptions induced by three opioid peptides against SP were significantly inhibited by D-Pro2-Tyr-W-MIF-1. These results suggest that differential inhibitory mechanisms on pre- and postsynaptic sites in the spinal cord contribute to the antinociceptive effects of the three mu-opioid peptides.
Watanabe
Hiroyuki
H
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Nakayama
Daisuke
D
Yuhki
Masayuki
M
Sawai
Toshiki
T
Sakurada
Wataru
W
Katsuyama
Sou
S
Hayashi
Takafumi
T
Watanabe
Chizuko
C
Mizoguchi
Hirokazu
H
Fujimura
Tsutomu
T
Sakurada
Tsukasa
T
Sakurada
Shinobu
S
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009294:Narcotics / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D000701:Analgesics, Opioid; D009294:Narcotics; D017450:Receptors, Opioid, mu; D013373:Substance P; D002211:Capsaicin