Rat/mouse hemokinin-1, a mammalian tachykinin peptide, markedly potentiates the antinociceptive effects of morphine administered at the peripheral and supraspinal level.
Rat/mouse hemokinin 1 (r/m HK-1) is a mammalian tachykinin peptide whose biological functions are not fully understood. Our recent report showed that i.c.v. administration of r/m HK-1 could produce dose- and time-related antinociceptive effect at nanomole concentration, and naloxone significantly antagonized this effect. Thus, we provide indirect evidence favoring a role of NK1 supraspinal receptors in the inhibitory control of descending pain pathways, a role that seems to partially involve the activation of the endogenous opioid systems. Based on this report, the present study was conducted to further investigate the direct functional interaction between supraspinal tachykinin (r/m HK-1) and opioid systems. The results demonstrate that i.c.v. administration of r/m HK-1 (5 nmol/kg) could significantly potentiate the antinociceptive effects of morphine which was injected at peripheral and supraspinal level. These antinociceptive effects were blocked by prior treatment with the classical opioid receptors antagonist naloxone, indicating that the potentiated analgesic response is mediated by opioid-responsive neurons. Consistent with previous biochemical data, a likely mechanism underlying the peptide-mediated enhancement of opioid analgesia may center on the ability of r/m HK-1 to release endogenous opioid peptides. We suggest that there may be a cascade amplification mechanism in pain modulation when the two agents were co-administrated. The synergistic analgesic relationship of morphine and r/m HK-1 established here supports the hypothesis that supraspinal tachykinin and peripheral and central opioid systems have a direct functional interaction in the modulation of local nociceptive responses.
Fu
Cai-Yun
CY
Department of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
Yang
Qi
Q
Wang
Kai-Rong
KR
Kong
Zi-Qing
ZQ
Chen
Qiang
Q
Wang
Rui
R
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004357:Drug Synergism; D007276:Injections, Intraventricular / Q000379:methods; D007279:Injections, Subcutaneous / Q000379:methods; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage*; D010147:Pain Measurement / Q000379:methods; D011498:Protein Precursors / Q000008:administration & dosage*; D011930:Reaction Time / Q000187:drug effects; D015320:Tachykinins / Q000008:administration & dosage*; D013997:Time Factors
D009292:Narcotic Antagonists; D009294:Narcotics; D011498:Protein Precursors; C423233:Tac4 protein, mouse; D015320:Tachykinins; D009270:Naloxone; D009020:Morphine