Involvement of purinoceptor expressed on M1 like macrophage in neuropathic pain

抄録

It is well known that macrophages are characterized by M1 like macrophages expressing inflammatory molecules (e.g. IL-1beta, iNOs) and M2 like macrophages expressing anti-inflammatory molecules (e.g. CD206, IL-10). Growing evidence suggests that the neuropathic pain, which is usually accompanied by neuro-inflammation, were improved by the manipulation of M1 like macrophage suppression at the injured nerve, using neuropathic pain model mice. Therefore, we assume that the cell surface molecules in M1 like macrophage accumulating at the injured nerve are important to develop the novel therapeutic agents for neuropathic pain. By Flow cytometry analysis, we separated into M1 like macrophage and M2 like macrophage due to the difference of cell surface molecules at the injured sciatic nerve in mice, and found that the expression level of ecto-ATPase in M1 like macrophages was significantly lower than that in M2 like macrophages. Since recent studies indicate that the increase in extracellular ATP stimulates the secretion of inflammatory molecules including IL-1 beta and PGE2 in M1 like macrophages through the activation of the P2X purinoceptors, we evaluated the expression levels of P2X1-7 mRNA at the injured nerve. By real-time PCR analysis, the expression levels of P2X4 and P2X7 mRNA at the injured sciatic nerve were increased more than those at intact sciatic nerve with accompanying the upregulation of Pannexin1 (PANX1; an ATP release channel). Although further studies are needed to determine whether P2X4, P2X7 and PANX1 are expressed on the surface of M1 like macrophages, we hypothesize that ATP-induced activation of P2X4 and P2X7 may involve in the development of neuropathic pain, and the ATP is released from M1 like macrophages by the activation of PANX1.