Manual Acupuncture, but not Electroacupuncture Stimulate Afferent Nerves through Activation of TRPV1 Receptors to Modulate Pressor Reflexes

We have shown that manual acupuncture (MA) at the P6 acupoint and electroacupuncture at the P5‐6 acupoints stimulate afferent fibers in the median nerve (MN) to modulate sympathoexcitatory cardiovascular reflexes through central regulation of autonomic function. However, mechanisms underlying MA and EA activation of these sensory afferents and their cell bodies in the dorsal root ganglia (DRG) are unknown. A histological study demonstrated that, compared to non‐acupoints, TRPV1 receptors are expressed in greater quantities in sensory nerve fibers located in the area of the ST36 acupoint. It remains unclear if TRPV1 receptors at the P5‐6 areas and DRG neurons contribute to activation of sensory nerves by MA and EA, leading to modulation of pressor responses. Therefore, in the present study, we investigated sensory neural mechanisms by which acupuncture inhibited cardiovascular responses. We hypothesized that acupuncture stimulates afferent nerves through activation of TRPV1 receptors to modulate pressor reflexes. In rats, we found that phasic single‐unit MN activity evoked by MA at P6 was significantly attenuated (P<0.05) by local administration of Iodoresiniferatoxin (a selective TRPV1 receptor antagonist, n=12), but not 5% Dimethyl sulfoxide (DMSO; vehicle, n=12) into the acupoint. Administration of Iodoresiniferatoxin into P5‐6 did not reduce EA‐evoked single‐unit MN activity (n=8). We also observed that MA at P6 and EA at P5‐6 induced phosphorylation of extracellular signal‐regulated kinases (ERK; an intracellular signaling messenger involved in cellular excitation) in DRG neurons at spinal levels of C6‐T1 that receive MN inputs. After knocking‐down of DRG TRPV1 receptors at these spinal levels with intrathecal injection of siRNA, expression of phosphorylated ERK in DRG neurons was reduced by MA, but not EA. Moreover, local injection of Iodoresiniferatoxin (n=5), but not 5% DMSO (n=5) into P6 reversed the inhibitory action of MA at this acupoint on pressor reflexes induced by gastric distension. However, the inhibitory effect of EA at P5‐6 on pressor responses evoked by gastric distension was not reversed after administration of Iodoresiniferatoxin into P5‐6 in two separate rats. Thus, these data suggest that MA, but not EA activate sensory afferents through stimulation of TRPV1 receptors to inhibit reflex increases in blood pressure. Support or Funding Information NIH grant AT009347