Involvement of the BNP/NPR-A/BKCa pathway in rat trigeminal ganglia following chronic constriction injury

Abstract

Accumulating evidence indicates that the brain natriuretic peptide (BNP) and its receptor (natriuretic peptide receptor, NPR) are widely distributed in a variety of tissues including trigeminal ganglion (TG). Furthermore, recent studies support the involvement of the BNP-NPR-A pathway in acute and chronic pain. To investigate the role of this pathway in chronic pain, an infraorbital nerve-chronic constriction injury (ION-CCI) model of trigeminal neuralgia (TN) was produced in the rat. The time course of changes in mechanical pain threshold was examined. We observed an upregulation of BNP and NPR-A and a downregulation of large-conductance Ca²⁺-activated K⁺ (BKCa) mRNA and protein in rats subjected to ION-CCI. Patch clamping experiments in vitro found that BKCa currents were significantly reduced in rats subjected to ION-CCI. BNP increased BKCa currents in ION-CCI rats. These results suggest that BNP and NPR-A might serve as endogenous pain relievers in ION-CCI rats. Modulation of the BNP/NPR-A/BKCa channel pathway in TG may be a viable strategy for the treatment of TN.NEW & NOTEWORTHY BNP has been known to activate its receptor, NPR-A, to modulate inflammatory pain. However, the potential modulatory roles of BNP in TN have not been investigated in detail. We established an ION-CCI model of TN in the rat and observed an upregulation of BNP and NPR-A and a downregulation of BKCa in rats subjected to ION-CCI. Moreover, BNP can increase BKCa currents in ION-CCI rats. Thus, BNP and NPR-A might have inhibitory effects on trigeminal neuralgia through activating the BNP/NPR-A/BKCa channel pathway.

Keywords: brain natriuretic peptide; chronic constriction injury; large-conductance Ca2+-activated K+ (BKCa) channel; neuropathic pain; trigeminal neuralgia.