NR1I2 and irritable bowel syndrome: Agonists of PARs excite spinal afferent neurons that innervate the GI tract.153,154 Biopsy supernatants from IBS patients have also been shown to excite spinal afferent neurons via PAR-2 activation.7,58,155 These excitatory effects have been ascribed to sensitization of transient receptor potential (TRP) channels, including TRPV1, TRPV4 and TRPA1 as well as suppression of voltage-gated K+ channels.