Pharmacology Biochemisto' & Behavior, Vol. 18, pp. 65-71, 1983. Printed in the U.S.A. Capsaicin Treatment and Stress-Induced Analgesia RICHARD J. BODNAR, DONALD A. SIMONE, JEFFREY H. KORDOWER, ANNETTE L. KIRCHGESSNER AND GAJANAN NILAVER* Department of Psychology, Queens College, CUNY, Flushing, N Y 11367 and *Department of Neurology, Columbia University College of Physicians and Surgeons, New York, N Y 10032 Received 29 June 1981 BODNAR, R. J.. D. A. SIMONE, J. H. KORDOWER, A. L. K1RCHGESSNER AND G. NILAVER. Capsaicin treat- ment and stress-induced analgesia. PHARMACOL BIOCHEM BEHAV 18(1) 65-71, 1983.--Capsaicin modulates animal pain perception, increasing chemosensitive and pressure thresholds following systemic administration, increasing thermal thresholds following intrathecal administration, and decreasing electric shock thresholds following intracerebroventicular(ICV) administration. Since morphine analgesia is decreased in a dose-dependent manner following ICV capsaicin, the present study examined whether ICV injections of capsaicin (0, 25, 50, 100 tzg) would alter other analgesic responses as well. Experiment 1 demonstrated that the analgesic response to a 450 mg/kg dose of 2- deoxy-D-glucose was significantly reduced by the 25 and 50, but not the 100/zg capsaicin dose. Further, while analgesia induced by cold-water swims (CWS) in a 2°C bath was significantly attenuated by the 25 p~gcapsaicin dose, the entire dose range eliminated analgesia induced by CWS in a 15°Cbath. Experiment 2 indicated that the capsaicin-induced alterations in CWS analgesia were not attributable to parallel changes in CWS hypothermia. Experiment 3 demonstrated that capsaicin failed to alter both the non-opioid analgesic response induced by 20 inescapable foot shocks (FS) and the opioid analgesic response induced by 80 FS. These data are discussed in terms of the similarities to and/or dissimilarities from capsaicin- induced effects upon morphine analgesia. Capsaicin Cold-Water swim analgesia Foot shock analgesia 2-deoxy-D-glucose analgesia Rats CAPSAICIN (CAP), the active ingredient of Mexican red peppers and Hungarian hot peppers, has been employed re- cently as an agent to modulate nociceptive thresholds. Sys- temic CAP injections produce an insensitivity to chemical [25] and pressure [20] stimuli in rats, effects which may be attributed to irritation around the injected area (see review: [42]). Thermal analgesia has been observed following CAP in normal rats following intrathecal [42], but not systemic [12] routes of administration. Furthermore, CAP increases hot- plate and tail-flick latencies in spontaneously hypertensive rats [41], produces thermal analgesia in guinea pigs [11] and impairs heat discrimination learning [33]. Neonatal adminis- tration of CAP also induces analgesic responses when these animals are tested as adults [12, 22, 32]. Initial observations indicated that CAP altered pain thresholds by producing a calcium-dependent release and subsequent depletion of substance P from spinal primary sensory neurons located in the superficial layers of the dorsal horn following systemic [11, 12, 18, 26, 28, 40], intrathecal [30,44] and intracisternal [24] administration in adults. A simi- lar pattern is observed in neonatally-treated animals receiv- ing systemic CAP [21, 31, 32]. Like substance P, CAP produced excitatory potentials when applied microion- tophoretically into the trigeminal nucleus caudalis [36]. However, despite the depletion of substance P by CAP pre- treatment, nociceptive units in the trigeminal nucleus caudalis were found to be unaffected [35]. Yet, C-fiber con- duction in the sciatic nerve is blocked by CAP [43]. Moreover, further studies have indicated that CAP pos- sessed multiple modes of action. These include depletion of somatostatin [30] from the dorsal horn, a decrease of opiate [17,32] and GABA [38] receptors on primary sensory neurons, and an increase in the tissue concentrations of his- tamine and serotonin [23]. In addition, cholecystokinin is depleted from the dorsal horn when CAP is administered systemically to adults [I,45], but not when it is administered to neonates [29,37]. The route of administration is another integral factor in assessing CAP's effects. Our laboratory [7] found that intra- cerebroventricular (ICV) injections of CAP produced a short-lived hyperalgesic effect on the flinch-jump test and decreased the analgesic response to morphine in a dose- dependent manner. Using immunocytochemical procedures, we found that ICV injections of CAP failed to alter substance P in either the periaqueductal gray, nucleus raphe magnus, medullary reticular formation, the dorsolateral funiculus or the superficial layers of the spinal cord and fifth cranial nerve. The present study examined whether ICV injections of CAP would alter other analgesic responses as well. These analgesic responses were chosen specifically because of their respective similarities to and differences from morphine analgesia, factors that will be discussed in further detail. Experiment 1 was designed to examine CAP's dose- dependent (0, 25, 50, 100/zg) effects following ICV injection upon the analgesic responses following 2°C and 15°C cold- water swims (CWS) as well as a 450 mg/kg dose of 2-deoxy-D-glucose (2DG). Since CAP decreases core body temperature [15, 27, 34] and neural responses to thermal Copyright ~: 1983 ANKHO International Inc.--0091-3057/83/010065-07503.00/0