Bradykinin modulation of a spinal nociceptive reflex in the rat

Bradykinin (BK) is a potent algesic compound. Therefore, we hypothesized that BK, acting as a peripheral noxious stimulus, would attenuate or inhibit responses to another noxious stimulus. When administered intravenously (i.v.) to rats lightly anesthesized with pentobarbital, BK produced a dose-dependent (12-144 micrograms/kg) inhibition of the nociceptive tail-flick (TF) reflex. BK also produced a dose-dependent decrease in mean arterial blood pressure, a subsequent increase in heart rate and an increase in the rate of respiration. The latency to the maximal effect of BK on the TF reflex was 10 s and was occasionally preceded by pseudoaffective responses at doses greater than 48 micrograms/kg BK. Neonatal treatment with capsaicin (50 mg/kg, subcutaneous) significantly attenuated BK-produced inhibition of the TF reflex indicating that BK was acting via peripheral afferents to inhibit the TF reflex. Reversible cold block or complete spinal transection at a low thoracic level (T9-12), but not reversible cold block at a high cervical level (C1-2), significantly attenuated BK-produced inhibition of the TF reflex, suggesting that BK activates afferents which enter the spinal cord between C2 and T9. Pretreatment with intrathecally administered phentolamine (30 micrograms), an alpha-adrenoceptor antagonist, or methysergide (30 micrograms), a non-selective serotonin receptor antagonist, did not alter BK-produced inhibition of the TF reflex, further supporting the absence of activation of descending systems from the brainstem by i.v. BK. While coadministration of PGE2 and BK significantly potentiated BK-produced inhibition of the TF reflex, neither bilateral removal of the stellate ganglion nor bilateral cervical vagotomy significantly affected the inhibitory action of i.v. BK on the TF reflex. These results suggest that i.v. BK inhibits the nociceptive TF reflex by activation of capsaicin-sensitive visceral afferents entering the spinal cord between C2 and T9.