The synergic effect of BK and ATP in peripheral nociceptive responses:an electrophysiological and behavioral study

Abstract

Objective To explore the responses and mechanisms of peripheral primary afferent neurons to adenosine 5'-triphosphate (ATP) and bradykinin (BK) applied separately or in combination by electrophysiological recording and behavioral observation. Methods The experiments were done on samples of acutely isolated rat dorsal root ganglion (DRG) neurons by the whole-cell patch clamp recording technique, to record ATP-activated current (IATP) and the regulating effect of BK on IATP and to observe the global behavior with pain behavioral experiment. Results ATP added after the pretreatment of BK in the majority of detected cells, IATP would be reinforced significantly, the degree of increment depending on the concentration of BK (BK 10-6 -10-4 mol/L), while the EC50 values of the concentration-response curve with and without pretreatment of BK were very close to each other (1.65×10-5 mol/L vs 2.0×10-5 mol/L). In the behavioral experiment, subcutaneously intraplantar injection of BK and ATP separately in hind limbs of rats both induced concentration-dependent pain behavioral (paw lifting) responses, while the duration of hindpaw lifting was prolonged dramatically with the increase in the ATP concentration, when BK (10-6 mol/L) was injected in combination with ATP (10-5, 10-4 and 10-3 mol/L). Conclusion Inflammatory mediators like BK and ATP etc play an important role in the production, transmission and modulation of pain information in peripheral sensory nerve endings. Both electrophysiological and behavioral experiments demonstrate that there is a synergic effect between ATP and BK, which is thought to be non-competitive. BK may reinforce IATP remarkably, and the pain responses induced by the increment in ATP concentration increase with the existence of BK. Key words: Rat dorsal root ganglion; Patch clamp recording technique; Behavioral experiment; Nociceptive response; ATP; Bradykinin