Endomorphin-2, deltorphin II and their analogs suppress formalin-induced nociception and c-Fos expression in the rat spinal cord.
In this study, we evaluated the effects of intrathecally administered agonists of mu- and delta-opioid receptor and their analogs on the pain-induced behavior and expression of c-Fos immunoreactivity in the spinal cord, elicited by intraplantar injection of 12% formalin to the hindpaw of the rat. Previous report from our laboratory and other author's study indicated that intrathecal administration of mu agonists morphine and endomorphin-2 and delta-opioid agonist deltorphin II produced a dose-dependent antinociceptive effects in acute and inflammatory pain. In this study, intrathecal injection of morphine (10 microg), endomorphin-2 (5 microg) and its analog Dmt-endomorphin-2 (10 microg) significantly decreased the formalin-induced pain behavior, and lowered a number of c-Fos positive neurons in the laminae I, II and III of the spinal cord by about 40%, 30% and 40%, respectively. Significant reduction of formalin-induced behavioral responses was also observed after i.th. administration of deltorphin II (15 microg) and its analog ile-deltorphin II (15 microg). Agonists of delta-opioid receptor significantly reduced a number of c-Fos positive neurons by about 28% and 40%, respectively. Analog of endomorphin-2 and analog of deltorphin II suppressed more potently expression of c-Fos in the dorsal horn of the spinal cord than the parent peptides. Our study indicates that new analogs of mu- and delta-opioid receptor exhibit strong antinociceptive potency similar or even higher than the parent peptides, and that their effect is positively correlated with the inhibition of c-Fos expression.
Labuz
Dominika
D
Department of Molecular Neuropharmacology, Institute of Pharmacology, 12 Smetna Street, 31-343 Kraków, Poland.
Chocyk
Agnieszka
A
Wedzony
Krzysztof
K
Toth
Geza
G
Przewlocka
Barbara
B
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000494:pharmacology*; D007249:Inflammation; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D009842:Oligopeptides / Q000096:biosynthesis* / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*; D013997:Time Factors
D000701:Analgesics, Opioid; D009842:Oligopeptides; D016760:Proto-Oncogene Proteins c-fos; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C059567:deltorphin; C060209:deltorphin II, Ala(2)-; D005557:Formaldehyde; C105294:endomorphin 2; D009020:Morphine