Long-lasting delayed hyperalgesia after subchronic swim stress

Rats subjected to an inescapable subchronic stress, consisting of 10-20 min of forced swimming for 3 days, showed a thermal hyperalgesia and an enhanc ed nociceptive behavior to the subcutaneous administration of formalin 24 a nd 48 h, respectively, after the last swim session. Hyperalgesia to thermal and chemical stimulants was still present 8 and 9 days after the last swim session, respectively. Chemical, but not thermal, nociception was negative ly correlated with the swim effort or struggle times during the last swim s ession. The serotonin-selective reuptake inhibitors clomipramine (2.5 mg/kg /day, i.p., started 3 or 7 days before stress) and fluoxetine (0.25 mg/kg/d ay, i.p., started 7 days before stress), or serotonin precursor tryptophan (3 mg/kg/day, i.p., 24 h before each swim stress) blocked the development o f both the thermal and the chemical hyperalgesia and increased swim effort times compared to vehicle-treated rats. These treatments did not affect noc iceptive responses in control rats subjected to sham swimming. These findin gs suggest that repeated stress can produce a long-lasting increase in pain sensitivity to both phasic or tonic noxious stimuli by diminishing central serotonin activity. This model may help elucidate the underlying neural me chanisms that mediate the effects of repeated stress on pain sensitivity an d affective states. (C) 2000 Elsevier Science Inc. All rights reserved.