Opiate self-administration as a measure of chronic nociceptive pain in arthritic rats.
The study examined the validity of oral fentanyl self-administration (FSA) as a measure of the chronic nociceptive pain that develops in rats with adjuvant arthritis independently of acute noxious challenges. Arthritic rats self-administered more of a 0.008 mg/ml fentanyl solution (up to 3.4 g/rat per day) than non-arthritic controls (0.5 g/rat per day) and did so with a biphasic time course that reached peak during weeks 3 and 4 after inoculation with Mycobacterium butyricum. The time course paralleled both the disease process and the chronic pain. Continuous infusion of dexamethasone during weeks 3 and 4 via subcutaneous osmotic pumps at 0.0025-0.04 mg/rat per day disrupted the arthritic disease and decreased FSA to a level (i.e. by 65%) similar to that observed in non-arthritic rats. Continuous naloxone (2.5 mg/rat per day) decreased FSA (by 55%) in arthritic but not in non-arthritic animals. Continuous, subcutaneous infusion of fentanyl also decreased arthritic FSA in a manner that varied with dose at 0.04-0.16 mg/rat per day doses, but leveled off at 47% of controls with 0.31 mg/rat per day. The effects of continuous fentanyl on arthritic FSA occurred only with those doses and dose-dependent dynamics with which fentanyl also induced dependence in non-arthritic rats. The findings indicate that pain, rather than the rewarding or dependence-inducing action of fentanyl mediates FSA in arthritic rats. Paralleling patient-controlled analgesic drug intake, FSA offers a specific measure allowing the dynamic effects of neurobiological agents to be studied in this unique animal model of persistent nociceptive pain.
Centre de Recherche Pierre Fabre, 17 Avenue Jean Moulin, 81106 cedex, Castres, France. francis.colpaert@pierre-fabre.com
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D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D001168:Arthritis / Q000503:physiopathology*; D001522:Behavior, Animal; D002908:Chronic Disease; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage* / Q000627:therapeutic use; D009619:Nociceptors / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods*; D010166:Palliative Care; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values; D012646:Self Administration; D019966:Substance-Related Disorders / Q000523:psychology; D013997:Time Factors
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D005283:Fentanyl