Figure 9

Schematic diagram of the proposed interface between mechanostimulation and biological signaling at acupoint. Manual acupuncture at acupoints causes tissue traction during manipulation and results in the activation of mechanosensitive TRPV1 on the cell membrane. This leads to two parallel sensing pathways: the neural and the non-neural cell initiated sensing pathways. (A) In the former, TRPV1 of nerves is stimulated after traction, which generates an action potential after channel opening. It is also possible that increased intracellular calcium leads to ATP release by hemichannels to the extracellular matrix (ECM) after TRPV1 stimulation. The released ATP acts in an autocrine manner and results in self-stimulation (neuron) by purinergic receptors (P2Y or P2X). (B) In the latter, TRPV1 on muscle fibers or fibroblasts is activated and increases calcium influx leading to ATP release to the ECM. The released ATP then activates purinergic receptors on nearby cells (another muscle fiber or fibroblast). This increases intracellular calcium again and another ATP is released. The chain-like paracrine process of ATP release and calcium signaling is named calcium wave propagation (CWP). As in other circumstances, non-neural cells can pass on message to neurons via CWP after traveling for a certain distance. The occurrence of antinociceptive regulation requires that these pathways activate noxious stimulus-induced analgesia (NSIA), either spinally (by inhibitory interneurons) or supraspinally [by the nucleus accumbens and descending inhibitory pathway (DIP)]. This hypothesis is supported by previous reports: ATP release during acupuncture (Goldman et al. [19] and Takano et al. [18]); CWP during acupuncture in non-neural cells (Li et al. [34]); signaling from non-neural cells to neurons via CWP (Furuya et al. [32] and Koizumi et al. [33]); and numerous reports on CWP and NSIA. Abbreviations: pannexin 1 (PanX 1); connexin 43 (Cx 43); noxious stimulus-induced analgesia (NSIA); descending inhibitory pathway (DIP).