In the present study we examined whether the descending facilitation from the rostral ventromedial medulla (RVM) is required for the enhancement of formalin-evoked nocifensive behavior following repeated forced swim stress. Rats were subjected to forced or sham swim stress for 3 days. Withdrawal latency to noxious thermal stimuli and mechanical withdrawal threshold to von Frey filaments did not change significantly in both groups at 24h after the last stress session. The forced swim stress showed significantly enhanced nocifensive behavior to the subcutaneous administration of formalin at 2 days after the last stress session (1330.1 +/- 62.8 s), compared to the sham swim (1076 +/- 102.4 s, p<0.05) and naive groups (825.9 +/- 83.2 s, p<0.01). The destruction of the RVM with ibotenic acid led to prevent the enhancement of formalin-evoked nocifensive behavior in the forced swim group. These findings suggest that the descending facilitation from the RVM may be involved in the enhancement of formalin-evoked nocifensive behavior following the forced swim stress. (C) 2010 Elsevier B.V. All rights reserved.