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

Abstract

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.

High-Efficacy 5-Hydroxytryptamine 1A Receptor Activation Counteracts Opioid Hyperallodynia and Affective Conditioning

“…The affective/motivational quality is evidenced by data that pain sustains conditioned preference/aversion and that pain relief reverses such conditioning (Colpaert et al, 1982(Colpaert et al, , 2001Johansen et al, 2001). Conditioned preference/aversion can offer a highly specific assessment of pain; in rats with adjuvant arthritis, the conditioned taste preference for an opioid is selectively associated with persistent pain, not with the physical dependence and intrinsic reward that opioids may also produce (Colpaert et al, 2001).…”

“…The affective quality of pain acts as a motivational drive (Scholz and Woolf, 2002); addiction is similarly characterized by affective qualities (Frenois et al, 2002) that drive opioid selfadministration (Shippenberg, 1993). Conversely, in the presence of pain, opioid self-administration is driven by pain relief (Colpaert et al, 2001). That opioids induce the affective/motivational quality of pain complements evidence that opioids induce the sensory quality of pain and like its sensory proalgesic effects, aversive affective/motivational effects of morphine in rat persist hours after a single injection (Parker et al, 2002).…”

“…The latter can be studied by determining the extent to which the association of an unconditioned stimulus with some taste/place results in conditioned aversion (CPA)/preference (CPP). Indeed, painful manipulations sustain such conditioning (Colpaert et al, 1982;Johansen et al, 2001), and pain relief effectively reverses the conditioned affective/motivational quality of pain (Colpaert et al, 2001. Thus, further experiments studied the actions of F 13640 on the putative affective/motivational quality of opioid pain in a threecompartment, "unbiased" place-conditioning paradigm (Caillé et al, 1999).…”

L’analgésie contrôlée avec patience: vers une meilleure compréhension des comportements d’auto-administration des analgésiques

“…However, despite a plethora of laboratory drug self-administration studies, mostly conducted in the context of abuse and dependence, very few have evaluated drug self-administration for the treatment of pain. Available evidence from over half a dozen chronic pain studies does suggest that opioid self-administration patterns are quite different for animals with chronic arthritic 15 or neuropathic 16 pain, as compared to control rats, suggesting a distinction between the analgesic and reinforcing effects of opioids. There are virtually no published laboratory studies on analgesic self-administration 17 shows how a more focused approach addresses some of the questions raised by Katz et al 6 regarding the impact of various psychological conditions that affect analgesic self-administration behaviour.…”

Pain-like behaviours in animals ? how human are they?

“…The cumulative intake of both solutions shows that a drop in the intake of sweetened solution is replaced by an increase in fentanyl intake, which indicates that arthritic rats self-medicate against ongoing pain. When rats are then administered a test drug, such as the synthetic glucocorticoid dexamethasone, and given a choice of either solution to ingest, a drop in fentanyl consumption combined with an increase in total fluid consumption indicates a preferential analgesic effect of the test drug against ongoing pain [30]. (d) Microsampling in conscious animals.…”