(628): Effects of pain and analgesia on intracranial self-stimulation (ICSS) in rats

Abstract

The effective management of pain continues to be major clinical problem. Current preclinical models of pain focus on the measurement of pain-evoked behavior, which may yield false positives. Our laboratory has focused on methods development for assays of pain-suppressed behavior, which may complement existing assays. The present study compared the effects of IP lactic acid injections and morphine pretreatments on the writhing response (a pain-evoked behavior) and intracranial self-stimulation (ICSS; a behavior that may be suppressed by pain). For the ICSS procedure, Sprague Dawley rats implanted with electrodes in the lateral hypothalamus were tested on a FR1 schedule of reinforcement to respond for electrical stimulation. Response rates were measured across a descending series of 15 current frequencies, and rate-frequency curves were determined. Acid-induced writhing was measured over 60 min in a separate group of animals. Both writhing and ICSS were evaluated under baseline conditions and after treatment with lactic acid (0.32-3.2 %, IP) and/or morphine (1.0-10 mg/kg, IP). Lactic acid produced time- and concentration-dependent increases in writhing, with peak writhes occurring at 20 min. and subsiding by 60 min. Lactic acid also produced rightward shifts in the ICSS curve rate-frequency curves and increased ICSS thresholds. However, lactic acid was more potent in evoking writhing than in suppressing ICSS. Morphine dose-dependently reduced acid-evoked writhing, and effects of morphine on acid-suppressed ICSS are being evaluated now. ICSS may be an especially useful assay for evaluation of pain-suppressed behavior, because it is often used to assess reward threshold and “hedonic state” in rodents. Accordingly, ICSS may be useful for exploring interactions between pain and depression.