抄録
A number of studies have shown that physical exercise improves neuropathic pain, but the exact mechanism underlying exercise–induced analgesia is not fully understood. It has been known that macrophages play important roles in the peripheral nervous system with regard to management of pain. Activated macrophages were categorized as M1 (classically activated) and M2 (alternatively activated), and several studies demonstrated that M1 macrophages are associated with the development of pain by releasing proinflammatory cytokines, while M2 macrophages are involved in the relief of pain via production of anti–inflammatory cytokines. Although these results suggest that M2 macrophages may contribute to exercise–induced analgesia, it has never been examined whether physical exercise changes phenotypes of activated macrophages in injured nerves, and thereby contributes to the attenuation of neuropathic pain. Therefore, we examined the effects of running exercise on the changes of macrophage polarity in injured sciatic nerve of neuropathic pain model mice. Male C57BL ⁄ 6J mice received partial sciatic nerve ligation (PSL) on the right sciatic nerves, and were divided into five groups: Naïve, PSL–Sedentary, PSL–Runner, Sham–Sedentary and Sham–Runner mice. The Runner mice ran at a speed of 7 m/min for 60 min/day, 5 days/week from 2 days after PSL operation. PSL–Sedentary mice developed remarkable mechanical allodynia and thermal hyperalgesia, but the pain behaviors were significantly attenuated in PSL–Runner mice. After PSL, the number of CD68+ M1 macrophages was increased in injured sciatic nerves, but running exercise induced significant decrease of these macrophages. On the other hand, the number of CD206+ M2 macrophages in PSL–Runner mice was significantly increased within the proximal parts of injured sciatic nerve compared with that of PSL–Sedentary mice. Changes in the ratio of macrophage subtypes (Intermediate, M1 and M2) indicated that running exercise increased both Intermediate and M2 subtypes within proximal parts of injured sciatic nerves. The present study indicated that running exercise attenuated neuropathic pain at least partly by changing balance between M1 and M2 macrophages in injured sciatic nerve, and suggested that activation of M2 macrophages may contribute to produce exercise–induced analgesia in neuropathic pain condition.
