Stress-induced muscle and cutaneous hyperalgesia: Differential effect of milnacipran

We previously demonstrated that repeated swim stress produces long-term cutaneous hyperalgesia in rats. We have now determined the effect of stress upon muscle nociception and the anti-nociceptive efficacy of the norepinephrine-serotonin reuptake inhibitor, milnacipran (MIL) in this model. Rats were subjected to either 10-20 min daily sessions of forced swimming (FS) for 3 days, or sham swimming (SS) or control (CT). Maximal forelimb grip strength and hot plate response latencies were estimated before and after the conditioning to assess muscle and thermal nociception, respectively. MIL (1-30 mg/kg/i.p.) or vehicle was started 7 days before the conditioning protocol. There were significant reductions in maximal grip strength and hot plate latencies only in FS/vehicle rats. Subsequent carrageenan administration (2 mg/75 μl each triceps) diminished grip strength in all groups 24 h later, with grip strength lower in FS/vehicle and SS/vehicle rats than in CT/vehicle rats. Treatment with MIL before the stress prevented the reduction in grip strength in all groups but it was ineffective in preventing FS-induced reductions in hot plate response latencies. Thus, repeated stress produces muscle hyperalgesia that can be pharmacologically dissociated from cutaneous hyperalgesia, suggesting that different mechanisms may underlie these two phenomena.