The role of delta-opioid receptor subtypes in neuropathic pain.
A large body of evidence suggests an important role of delta-opioid receptor agonists in antinociception at the level of the spinal cord. Our study was undertaken to analyse the spinal antinociceptive and antiallodynic effects of delta(1)- and delta(2)-opioid receptor agonists and antagonist after their acute and chronic intrathecal administration in a neuropathic pain model in the rat. In rats with a crushed sciatic nerve, the delta(1)-opioid receptor agonist [D-Pen(2), D-Pen(5)]enkephalin (DPDPE, 5-25 microg i.t.) and the delta(2)-opioid receptor agonist deltorphin II (1.5-25 microg i.t.) dose dependently antagonized the cold-water allodynia which developed after sciatic nerve injury. These effects of DPDPE were antagonized by 7-benzylidenenaltrexon (BNTX, 1 microg i.t.) while the effects of deltorphin II were antagonized by 5'naltrindole izotiocyanate (5'NTII, 25 microg i.t.). Both agonists had a dose-dependent, statistically significant effect on the tail-flick latency in two tests, with focused light and cold water. Chronic administration of DPDPE (25 microg i.t.) and deltorphin II (15 microg i.t.) resulted in significant prolongation of the reaction time determined on days 2, 4 and 6 post-injury. In conclusion, our results show an antiallodynic and antinociceptive action of DPDPE and deltorphin II at the spinal cord level, which suggests that both delta-opioid receptor subtypes play a similar role in neuropathic pain. This indicates that not only delta(1)- but also delta(2)-opioid receptor agonists can be regarded as potential drugs for the therapy of neuropathic pain.
Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Cracow, Poland.
J
J
Mika
R
R
Przewłocki
B
B
Przewłocka
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001597:Benzylidene Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009437:Neuralgia / Q000503:physiopathology* / Q000517:prevention & control; D009842:Oligopeptides / Q000494:pharmacology; D010147:Pain Measurement; D020033:Protein Isoforms / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries; D013997:Time Factors
D000701:Analgesics, Opioid; D001597:Benzylidene Compounds; D017879:Isothiocyanates; D009292:Narcotic Antagonists; D009842:Oligopeptides; D020033:Protein Isoforms; D017465:Receptors, Opioid, delta; C060209:deltorphin II, Ala(2)-; C064283:naltrindole 5'-isothiocyanate; C077358:7-benzylidenenaltrexone; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-