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.
Colpaert
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Centre de Recherche Pierre Fabre, 17 Avenue Jean Moulin, 81106 cedex, Castres, France. francis.colpaert@pierre-fabre.com
Tarayre
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JP
Alliaga
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Bruins Slot
L A
LA
Attal
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Koek
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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