Antisera against endogenous opioids increase the nocifensive response to formalin: demonstration of inhibitory beta-endorphinergic control.

The roles of endogenous opioid peptides in the brain in the modulation of nocifensive responses to formalin in ICR mice were studied. Mice were pretreated intracerebroventricularly (i.c.v.) with rabbit antiserum against beta-endorphin, [Leu5]enkephalin, [Met5]enkephalin or dynorphin A-(1-17) 1 h prior to intraplantar injection of formalin (0.5%, 25 microl) and the nocifensive licking responses were then observed. Pretreatment of mice with antiserum against beta-endorphin enhanced the second phase, but not the first phase of the nocifensive responses to formalin. Pretreatment with antiserum against [Leu5]enkephalin also caused a small but statistically significant enhancement of the second phase, but not the first phase of nocifensive responses to formalin. On the other hand, pretreatment with antiserum against [Met5]enkephalin or dynorphin A-(1-17) did not affect the nocifensive response to formalin. Our results indicate that beta-endorphinergic, and to a lesser extent, [Leu5]enkephalinergic systems are activated at the supraspinal sites to attenuate the nocifensive responses to formalin stimulation.