Chemical irritation of the prostate sensitizes P2X3 receptor‐mediated responses in rat dorsal root ganglion neurons

Abstract

P(2)X(3) (ATP-gated receptors) in nociceptive neurons of dorsal root ganglion (DRG) participate in transmission of pain signals from the periphery to the spinal cord. However, the role of P(2)X(3) receptors in chronic prostate pain and continued intractable pain remains unclear. We examined ATP-evoked responses and P(2)X(3) expression in DRG neurons isolated from rats with prostatic inflammation induced by injection of complete Freund's adjuvant (CFA) into the prostate. Neurons were dissociated from the L(6)-S(1) DRG. The effect of ATP on the excitability of DRG neurons was determined using whole-cell patch clamp. P(2)X(3) receptor expression was determined with Western blot on the 3rd and 10th days after irritation of the prostate. Although application of ATP induced both fast- and slow-inactivating currents and caused depolarization in control and inflamed neurons, compared to the control group, the increase in ATP responses gave rise to large depolarization that exceeded the threshold of action potentials in inflamed DRG neurons. The affinity of P(2)X(3) receptor for ATP increased significantly and inflammation enhanced the expression of P(2)X(3) receptor in inflamed neurons. P(2)X(3) receptor upregulation could account for neuronal hypersensitivity and contribute to abnormal pain responses associated with chronic prostatitis. These results suggest that P(2)X(3) receptors are useful targets for the treatment of pain in chronic prostatitis.