Local peripheral effects of mu-opioid receptor agonists in neuropathic pain in rats.
Our study was designed to demonstrate peripheral antinociception of the mu-opioid receptor agonists: morphine (MF), [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]enkephalin (DAMGO), endomorphin-1 (EM-1) and endomorphin-2 (EM-2) in Bennett's rat model of neuropathic pain. All the agonists were effective in antagonizing allodynia after their intraplantar (i.pl.) but not subcutaneous (s.c.) administration. Opioid peptides: DAMGO, EM-1 and EM-2 were more effective compared with corresponding doses of morphine (opioid alkaloid) in alleviating chronic pain. Peripheral mu-opioid receptors mediated the observed effects, as was evidenced by the i.pl. treatment with naloxone methiodide (active only at the site of injection) and by cyprodime, a selective mu-opioid receptor antagonist. These results have shown that opioid peptides are effective also after local treatment, and that their peripheral use may be of therapeutic interest in long-term management of chronic pain.
Obara
Ilona
I
Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland.
Przewlocki
Ryszard
R
Przewlocka
Barbara
B
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000502:physiology; D020426:Sciatic Neuropathy / Q000188:drug therapy*
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu