Mechanism of dorsal root ganglion SERT in electroacupuncture regulation of P2X3 receptor-mediated visceral hypersensitivity in IBS rats

To investigate the role of serotonin reuptake transporter (SERT) and P2X3 receptor of dorsal root ganglion (DRG) in regulating visceral hypersensitivity of rats with irritable bowel syndrome (IBS) by electroacupuncture (EA).

Male Sprague-Dawley and SERT^−/− rats were subjected to preparing IBS visceral hypersensitivity models with 2,4,6-trinitrobenzene sulfonic acid (TNBS) enema. Three weeks post-modeling, interventions including EA, intrathecal injection, and EA plus intrathecal injection were applied, respectively. Hematoxylin-eosin staining and abdominal withdrawal reflex (AWR) score were used to confirm the successful establishment of the IBS model. AWR score, whole-cell patch clamp technique, and Western blotting assay were used to evaluate the changes in visceral pain sensitivity, electrophysiological properties of DRG neurons, and the expression of DRG P2X3 receptor and SERT in IBS rats.

Compared to the model group, the AWR score in the EA group decreased significantly (P<0.05), the resting membrane potential (P<0.05) and the number of action potentials (P<0.05) of DRG neurons reduced, and the baseline intensity increased (P<0.05); additionally, the expression of P2X3 receptor in DRG decreased (P<0.01), and the SERT expression increased (P<0.05). Compared to the P2X3 receptor agonist group, the SERT protein expression in DRG was higher in the EA group. In SERT^−/− rats, the P2X3 receptor expression in DRG increased in the EA group compared to the model group (P<0.01).

EA modulates the electrophysiological characteristics of intestinal primary sensory neurons by regulating the expression of SERT and P2X3 receptor in DRG of IBS rats. This modulation may contribute to the mechanism by which EA alleviates peripheral sensitization of visceral pain in IBS rats.