Brain sites involved in the antinociceptive effect of bradykinin in rats

The localization of brain sites where bradykinin (BK) induces its antinociceptive effect in rats, was studied using as index the threshold for the jaw‐opening reflex elicited by the dental pulp electrical stimulation test (DPEST). The microinjection of BK into the lateral or fourth cerebral ventricles induced an antinociceptive effect, with Index of Antinociception (IA) of 0.51±0.03 and 0.68±0.05, respectively. However, microinjections of the peptide into the third ventricle induced a less marked antinociception (IA=0.28±0.08). The brain sites where the microinjection of BK caused an antinociceptive effect were: locus coeruleus , principal nucleus, oral part of the spinal sensorial trigeminal nucleus, and the sensory root of the trigeminal nerve. The antinociceptive effect was more intense when BK (4–16 nmol) was injected into the locus coeruleus . Microinjection of BK (4 nmol) into the fourth ventricle, but not into the locus coeruleus , induced an increase in blood pressure. The microinjection of the peptide into the nucleus tractus solitarius , a site that is also involved in the pressor effect of BK, did not induce an antinociceptive effect. These results indicate that the antinociceptive effect of BK is not related to blood pressure changes. The microinjection of BK into some of the sites involved in the mechanisms of analgaesia, including the periaquenductal gray matter (dorsal, lateral and ventrolateral) and the dorsal raphe nucleus did not induce an antinociceptive effect. The results suggest that the most likely brain sites involved in the antinociceptive effect of BK are the locus coeruleus and the principal sensory trigeminal nucleus. The present results did not exclude the involvement of other brain sites surrounding the lateral and the third ventricles.British Journal of Pharmacology (1998) 125 , 1578–1584; doi: 10.1038/sj.bjp.0702209