Role of TRPV1 in acupuncture modulation of reflex excitatory cardiovascular responses

Abstract

We have shown that acupuncture, including manual and electroacupuncture (MA and EA), at the P5-6 acupoints stimulates afferent fibers in the median nerve (MN) to modulate sympathoexcitatory cardiovascular reflexes through central regulation of autonomic function. However, the mechanisms underlying acupuncture activation of these sensory afferent nerves and their cell bodies in the dorsal root ganglia (DRG) are unclear. Transient receptor potential vanilloid type 1 (TRPV1) is present in sensory nerve fibers distributed in the general region of acupoints like ST36 and BL 40 located in the hindlimb. However, the contribution of TRPV1 to activation of sensory nerves by acupuncture, leading to modulation of pressor responses, has not been studied. We hypothesized that TRPV1 participates in acupuncture's activation of sensory afferents and their associated cell bodies in the DRG to modulate pressor reflexes. Local injection of iodoresiniferatoxin (Iodo-RTX; a selective TRPV1 antagonist), but not 5% DMSO (vehicle), into the P6 acupoint on the forelimb reversed the MA's inhibition of pressor reflexes induced by gastric distension (GD). Conversely, inhibition of GD-induced sympathoexcitatory responses by EA at P5-6 was unchanged after administration of Iodo-RTX into P5-6. Single-unit activity of Group III or IV bimodal afferents sensitive to both mechanical and capsaicin stimuli responded to MA stimulation at P6. MA-evoked activity was attenuated significantly ( P < 0.05) by local administration of Iodo-RTX ( n = 12) but not by 5% DMSO ( n = 12) into the region of the P6 acupoint in rats. Administration of Iodo-RTX into P5-6 did not reduce bimodal afferent activity evoked by EA stimulation ( n = 8). Finally, 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 located at C spinal levels receiving MN inputs. After TRPV1 was knocked down in the DRG at these spinal levels with intrathecal injection of TRPV1-siRNA, expression of phosphorylated ERK in the DRG neuron was reduced in MA-treated, but not EA-treated animals. These data suggest that TRPV1 in Group III and IV bimodal sensory afferent nerves contributes to acupuncture inhibition of reflex increases in blood pressure and specifically plays an important role during MA but not EA.

Reply to “Letter to the Editor: Acupuncture is not a unique explanation for reflex excitatory cardiovascular responses”

“…The method used for manual acupuncture in our study (at~2 Hz for 5 min every 10 min during a 30-min period) has been reported in many other papers (1,16). Importantly, we observed increased discharges of the afferent fiber in the median nerve during manual acupuncture stimulation, while the afferent activity stopped after manual acupuncture (2). Thus, we believe that neural pathways involved in acupuncture stimulation mainly contribute to acupuncture's action in the regulation of cardiovascular function.…”

“…This assumption is supported by numerous publications (6,7,9,10,14). In addition, as we have addressed in our paper, not only mechanical stimulation, but also the chemical substances generated during the insertion and/or manipulation of the acupuncture needle, likely contribute to activation of sensory afferent nerves that send inputs to the central nervous system, leading to regulation of cardiovascular function (2).…”

“…Thus, in this study, we have focused on investigating the specific effect of acupuncture at P5-6 compared with the sham control in which the acupuncture needle was placed at the acupoint without either mechanical rotation or electrical stimulation. We observed that the sham acupuncture did not activate somatic sensory afferents and inhibited sympathoexcitatory cardiovascular reflexes (2). Furthermore, the sham control used in our study is highly recommended by the United States and international acupuncture societies for the experimental study of acupuncture because it can reduce a number of confounding factors compared with other types of controls (3).…”

Fos‐CreER‐based genetic mapping of forebrain regions activated by acupuncture

“…The P6 acupoint is located on the forelimb 1.0 mm above the flexor crease in the paw overlying the median nerve (Figure ) (Hua, ). MA (~2 Hz) applied at this acupoint evokes median nerve discharge and attenuates reflex cardiovascular responses (Guo, Fu, Su, Tjen‐A‐Looi, & Longhurst, ; Zhou, Fu, Tjen‐A‐Looi, Li, & Longhurst, ). A stainless steel acupuncture needle (40‐gauge, 0.16 × 15 mm) was inserted (2–3 mm) at P6.…”

Letter to the Editor: Acupuncture is not a unique explanation for reflex excitatory cardiovascular responses

“…TO THE EDITOR: Acupuncture is a traditional form of Asian medicine; theoretically the practice involves inserting a needle at the invisible acupoints on the top of the skin for therapeutic purposes. In a recent article by Guo et al (1), it was reported that manual acupuncture on the wrist area of rats in which the P6 acupoint was the proposed site and the median nerve was anatomically located, contributed to the inhibition of reflex increases in blood pressure, when compared with electrical and sham acupuncture. In this letter, I express my opinions, respectfully, on the findings.…”