Restraint reduces formalin-test pain but the effect is not influenced by lesions of the hypothalamic paraventricular nucleus.

Previous research indicates that the paraventricular nucleus of the hypothalamus (PVN) plays an important role in the development of stress-induced analgesia (SIA). Research implicating the PVN in SIA has generally employed the cold-water swim as the stressor and a phasic pain test, such as the tail-flick test, as the pain model. The present study, using the formalin test for tonic pain, investigated the effect of PVN lesions on (1) tonic pain responses and (2) SIA caused by 30 min of restraint. Male Long-Evans rats were randomly assigned to one of four groups. Two groups received electrolytic lesions of the PVN and two additional groups served as sham-operated controls. One group which received PVN lesions and one group which was sham-operated were exposed to 30 min of restraint immediately prior to a 0.05-ml injection of 2.5% formalin into the planter surface of one hindpaw. The remaining groups which either received PVN lesions or were sham-operated received the formalin injection without prior exposure to restraint. During the first phase of the formalin response, PVN lesions did not alter duration of paw elevation scores, but significantly increased duration of paw licking scores. A 30-min period of restraint had no effect on duration of paw elevation scores, but significantly decreased duration of paw licking scores. PVN lesions did not alter the significant decrease in paw licking scores as a result of restraint. During the second phase of the formalin response, PVN lesions did not alter either the duration of paw elevation scores or the duration of paw licking scores. A 30-min period of restraint significantly decreased duration of paw elevation scores, but had no effect on duration of paw licking scores. PVN lesions did not alter the significant decrease in paw elevation scores as a result of restraint. The results indicate that PVN lesions increase paw licking only during the first phase of the formalin response, with no other alterations in paw licking or duration of paw elevation. In addition, a 30-min period of restraint can produce short-term and long-term SIA for tonic pain. The short-term SIA is reflected as a decrease in paw licking, whereas the long-term SIA is reflected as a decrease in paw elevation. In addition, PVN lesions failed to alter SIA during both phases of the formalin test. The differential effect of restraint on pain responses during the two phases of the formalin test and the lack of effect of PVN lesions on SIA for tonic pain suggest that stress engages multiple endogenous pain inhibitory systems.