CONDITIONED PLACE PREFERENCE PARADIGM - A NOVEL-APPROACH FOR ANALGESIC DRUG ASSESSMENT AGAINST CHRONIC PAIN

In response to concerns over the clinical relevance of analgesic testi ng paradigms which involve acute nociceptive stimuli, the present rese arch examined the utility of the conditioned place preference (CPP) pa radigm as a novel approach for determination of analgesic drug efficac y against chronic nociception. Rats display preferences for environmen ts that have been previously paired with positively reinforcing drugs; whether place preference to the negatively reinforcing effects of ana lgesic drugs in an animal model of chronic pain occurs is yet unknown. The present research sought to determine whether animals experiencing chronic pain would display a place preference for an environment pair ed with analgesic drug treatment. Persistent inflammatory nociception was induced by unilateral injections of complete Freund's adjuvant (0. 1 mi) into the rat hind paw. Place preference to the opiate agonist mo rphine, the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the non-steroidal anti-inflammatory drug (NSAID) indomethacin was exa mined in 3 separate experiments. Rats received 8 counterbalanced condi tioning trials (4 drug, 4 no-drug) of 60 min each with various drug do ses (morphine: 3.0 and 10.0 mg/kg; indomethacin: 2.5 and 5.0 mg/kg; MK -801: 0.03, 0.1 and 0.3 mg/kg, i.p.) or vehicle serving as the reinfor cing stimuli in a 3 compartment (2 stimuli, 1 neutral) place preferenc e apparatus. In general, morphine place preference was observed in bot h inflamed and non-inflamed groups; inflamed groups exhibited enhanced morphine place preference than non-inflamed groups. MK-801 produced a low-dose place preference in inflamed animals; higher doses of MK-801 produced a place aversion in both inflamed and non-inflamed groups. I ndomethacin failed to produced place preference in either inflamed or non-inflamed groups. These data demonstrate that the negatively reinfo rcing properties of analgesic drugs can be assessed via the CPP paradi gm. In addition, this paradigm offers greater clinical relevance as an imals determine drug efficacy without the involvement of high-intensit y, phasic nociceptive stimulation.