Spinorphin, an endogenous inhibitor of enkephalin-degrading enzymes, potentiates leu-enkephalin-induced anti-allodynic and antinociceptive effects in mice.
Spinorphin (LVVYPWT) has been isolated from the bovine spinal cord as an endogenous inhibitor of enkephalin-degrading enzymes. It has been reported that spinorphin has an antinociceptive effect, inhibitory effect on contraction of smooth muscle and anti-inflammatory effect. In the present study, the effects of leu-enkephalin and spinorphin on allodynia and mechanical and thermal nociceptions were examined in vivo using mice. Intrathecal (i.t.) administration of leu-enkephalin or spinorphin inhibited the allodynia induced by intrathecal nociceptin in a dose-dependent manner. Furthermore, spinorphin enhanced the inhibitory effect of enkephalin on allodynia induced by nociceptin. Naloxone antagonized both inhibitory effects of leu-enkephalin and spinorphin, suggesting that the endogenous opioidergic system can modulate allodynia. Intracerebroventricular (i.c.v.) administration of leu-enkephalin increased the nociceptive threshold of heat or mechanical stimulation to a mouse. Although i.c.v. administration of spinorphin had no effect on the threshold of heat or mechanical stimulation, spinorphin enhanced and prolonged the antinociceptive effect of leu-enkephalin. The enhancement of spinorphin on the antinociception produced by leu-enkephalin was reversed by pretreatment with naloxone. From these results, it is suggested that the effects of spinorphin on enkephalin-induced anti-allodynic and antinociceptive effects are due to inhibition of enkephalin-degrading enzymes.
Honda
M
M
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Okutsu
H
H
Matsuura
T
T
Miyagi
T
T
Yamamoto
Y
Y
Hazato
T
T
Ono
H
H
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D004743:Enkephalin, Leucine / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D009619:Nociceptors / Q000187:drug effects; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology*; D018847:Opioid Peptides / Q000009:adverse effects / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D011480:Protease Inhibitors / Q000009:adverse effects / Q000494:pharmacology*
D000700:Analgesics; D009842:Oligopeptides; D018847:Opioid Peptides; D011480:Protease Inhibitors; C082392:spinorphin; D009270:Naloxone; D004743:Enkephalin, Leucine; D015260:Neprilysin