Effects of corticoliberin CRF(4-6) fragment on pain sensitivity in rats.

The effects of the tripeptide fragment corticoliberin CRF(4-6) (Pro-Pro-Ile) on pain sensitivity were studied in rats using the hotplate method. CRF(4-6) given centrally (6, 30, and 150 nmol/rat) had dose-dependent antinociceptive actions: the latent period of the paw-licking response increased by 7.4 +/- 1.4, 10.1 +/- 1.5, and 16.7 +/- 4.2 sec from the control level of 10.2 +/- 0.9 sec. The durations of the effect were 30 min for CRF(4-6) at a dose of 6 nmol and 60 min for doses of 30 and 150 nmol of tripeptide. Administration of the corticoliberin antagonist alpha h CRF(9-41) (centrally, 6.5 nmol) 60 min before tripeptide completely blocked the antinociceptive effects of CRF(4-6) (6 nmol). Thus, corticoliberin receptors are involved in mediating the antinociceptive influence of CRF(4-6). It can be suggested that the tripeptide either directly interacts with corticoliberin receptors or modulates the activity of CRFergic neurons.