Paradoxical effects of intracerebroventricular low-dose opioid antagonists in SHR with chronic pain.
The aim of our study was to investigate the effect of intracerebroventricular (i.c.v.) administration of very low doses of opioid antagonists on the pain threshold, arterial blood pressure and body temperature of spontaneously hypertensive rats (SHR) with chronic pain. We found that low doses of i.c.v. administered naloxone hydrochloride (0.3 microg) or naloxone methiodide (0.4 microg) produce paradoxical hypoalgesia. Similar results were not observed following i.c.v. administration of nor-binaltorphimine (0.6 microg). A paradoxical increase in the severity of hypertension followed i.c.v. opioid antagonist administration. This suggests an involvement of the opioid system in the mechanisms of blood pressure control. The paradoxical results obtained both for pain threshold and blood pressure after low doses of some opioid antagonists seem to confirm the role played by opioid autoreceptors in these effects. Existence of autoreceptors is suggested. Results obtained following i.c.v. administration of nor-binaltorphimine also suggest a role for the kappa autoreceptor (OP2) in the regulatory mechanisms of thermoregulation.
Department of Pharmacodynamics, Medical University, Warsaw, Poland. kolaricsasa@hotmail.com
S
S
Kolaric
H E
HE
Makulska-Nowak
S W
SW
Gumułka
K
K
Mizerska
D000698:Analgesia; D000818:Animals; D001158:Arteries; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002908:Chronic Disease; D006973:Hypertension / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D000644:Quaternary Ammonium Compounds; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C041269:N-methylnaloxone