Opiate self-administration as a measure of chronic nociceptive pain in arthritic rats

Pain. 2001 Mar;91(1-2):33-45. doi: 10.1016/s0304-3959(00)00413-9.


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.

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use
  • Animals
  • Arthritis / physiopathology*
  • Behavior, Animal
  • Chronic Disease
  • Fentanyl / administration & dosage
  • Fentanyl / adverse effects
  • Fentanyl / therapeutic use
  • Male
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Narcotics / administration & dosage*
  • Narcotics / therapeutic use
  • Nociceptors / physiopathology*
  • Pain / drug therapy
  • Pain / physiopathology
  • Pain Measurement / methods*
  • Palliative Care*
  • Rats
  • Rats, Inbred Lew
  • Reference Values
  • Self Administration
  • Substance-Related Disorders / psychology
  • Time Factors


  • Analgesics, Opioid
  • Narcotic Antagonists
  • Narcotics
  • Naloxone
  • Fentanyl