Study on mechanisms of changes of TTX-R/TTX-S sodium channels in dorsal root ganglion neurons after acupoint sensitization induced by myocardial ischemia in mice

To explore the relation between acupoint sensitization and alterations of electrical signals of dorsal root ganglion (DRG) neurons from the perspective of ion channel dynamics in myocardial ischemia (MI) model mice.

Sixty-four male C57BL/6J mice were randomly assigned to control and model groups (n=32/group). The MI model was established by ligation of the left anterior descending (LAD) of the coronary artery. The MI was monitored by observing changes of ST segment of the standard limb-lead Ⅱ of electrocardiogram (ECG-ST_Ⅱ). 2, 3, 5-triphenyltetrazolium chloride (TTC) and H.E. staining were used to evaluate the infarct area and histopathological changes in the myocardial tissue. Evans blue (EB) staining was administered via tail vein injection to observe the location, distribution, and quantity of exudate points on the body surface in both groups. Nociceptive changes were evaluated by measuring mechanical pain and thermal pain thresholds. Subsequently, electrophysiological assessments were conducted in vitro to evaluate whole-cell membrane currents, intrinsic excitability, and Na⁺ channel current variations in different types of DRG neurons.

Compared with the control group, the ECG-ST_Ⅱ segment in the model group was significantly elevated (P＜0.0001), suggesting an induction of MI. TTC and H.E. staining showed a significant increase in the MI area (P＜0.001), accompanied by evident histopathological features such as myocardial fiber damage and inflammatory cell infiltration. The number of EB exudate points was significantly increased (P＜0.01), mainly distributing in the skin innervated by the T1—T5 spinal cord segments, as well as in the acupoints of “Feishu” (BL13), “Jueyinshu” (BL14) and“Xinshu” (BL15). Mechanical retraction reflex thresholds of the left upper and lower limbs of the model group significantly reduced (P＜0.0001), and the thermal retraction latency of the left upper and lower limbs were notably shortened in the model group (P＜0.01, P＜0.0001), and the mechanical pressure pain threshold on the left dorsal skin significantly reduced (P＜0.001). The DRG medium-sized neurons displayed an obvious decrease in rheobase (P＜0.05), along with a notable increase in whole-cell membrane current, spike number, and average instantaneous frequency (P＜0.05), reflecting enhanced intrinsic excitability. The activation curves of TTX-R/TTX-S sodium channels shifted towards hyperpolarization (P＜0.001), while the inactivation curves moved towards depolarization (P＜0.01).

DRG medium-sized neurons in the T1—T5 spinal cord segments may influence the acupoint sensitization of the body surface by modifying their Na⁺ channel kinetic properties.