Research report Strain and sex differences in the expression of nociceptive behavior and stress-induced analgesia in rats Leandro Franco Vendruscolo, Fabrı ´cio Alano Pamplona, Reinaldo Naoto Takahashi * Departamento de Farmacologia, Centro de Ciencias Biolo ´gicas, Universidade Federal de Santa Catarina (CCB-UFSC), Campus Universita ´rio Trindade 88040-900, Floriano ´polis, SC, Brazil Accepted 19 October 2004 Available online 11 November 2004 Abstract Evidence indicates that genetic, gender, and emotional/attentional aspects modulate the pain sensation. The present study examined the effect of swim-stress on nociceptive responses in Lewis (LEW) and spontaneously hypertensive (SHR) inbred rats (contrasting for anxiety- related behaviors), as well as in Wistar (WIS) rats of both sexes. Furthermore, we explored possible neurochemical mechanisms involved. In addition, we investigated whether habituation in the hot-plate apparatus could modify the hypoalgesic phenotype of SHR. Male and female LEW, SHR, and WIS rats were tested immediately before and 2 min after a 3-min swim in 15 8C water. The swim-stress induced analgesia in LEW and WIS, but not in SHR male rats. The same stressor induced analgesia in females of all three strains. In WIS female rats, the stress- induced analgesia (SIA) seems to involve, at least partially, a nonopioid N-methyl-d-aspartate (NMDA) analgesic system. Moreover, five brief exposures (90 s; 10-min intertrial interval) to the unheated hot-plate apparatus completely abolished the differences in basal hot-plate latencies observed in SHR compared with LEW and WIS strains. The present results demonstrate genetic and gender differences in nociceptive sensitivity and in the activation of endogenous analgesic systems in rats and highlight the influence of emotional reactivity. The SHR’s hypoalgesic phenotype seems to involve central cognitive processes. Therefore, the LEW and SHR inbred strains may provide an important tool for study of the molecular bases underlying nociception and its modulation and the relationship with emotional/attentional processes. D 2004 Elsevier B.V. All rights reserved. Theme: Sensory systems Topic: pain modulation: pharmacology Keywords: Nociception; Analgesia; Swim-stress; Naltrexone; MK-801; NMDA-receptor; Novelty; Habituation 1. Introduction Pain is an important sensorial modality with an elevated degree of complexity and subjectivity that involves not only the transduction of noxious stimuli, but also cognitive and emotional features [38]. Moreover, the influence of genetic factors on the pain sensation and its modulation has been widely demonstrated in laboratory animals and in humans [32]. This genetic component is likely to be partially responsible for the interindividual variation observed in pain-related behaviors. Therefore, the utilization of genetic models for the study of nociception and analgesia (e.g., inbred rat strains) may improve current understanding about pain-related processes and open new perspectives for the pain-relief therapies in humans. The exposure of animals to a variety of stressful events can activate endogenous analgesic systems, a phenomenon named bstress-induced analgesiaQ (SIA). The SIA may be opioid or nonopioid in nature [18] based on its reversi- bility by naloxone and/or cross-tolerance expression with morphine. Whether the analgesia is opioid or nonopioid in nature depends on stress severity, pain test employed, sex, 0006-8993/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2004.10.016 * Corresponding author. Tel.: +55 48 331 9764; fax: +55 48 337 5479. E-mail address: takahashi@farmaco.ufsc.br (R.N. Takahashi). Brain Research 1030 (2004) 277 – 283 www.elsevier.com/locate/brainres