Insufficient efferocytosis by M2-like macrophages as a possible mechanism of neuropathic pain induced by nerve injury.

Peripheral nerve injury typically leads to chronic inflammation through recruitment of immune cells, which may induce neuropathic pain. We previously reported that M1-like macrophages at sites of peripheral nerve injury induced neuropathic pain; however, the involvement of other immune cells (e.g. M2-like macrophages) in the progression of neuropathic pain remains unclear. In addition, the immune responses that occur at sites of nerve injury have not been well characterized. In this study, we show that M2-like macrophages accumulate in injured nerves to participate in the clearance of dead or dying cells (i.e., efferocytosis). Because MerTK (a receptor of dead or dying cells) levels on the surface of macrophages are limited, it seems to induce the insufficient of efferocytosis, such that the levels of dead or dying cells cannot be controlled in injured nerves. Given that efferocytosis is pivotal for resolution of inflammation, our data suggest that insufficient efferocytosis is a contributing factor in the development of chronic inflammation in injured nerves.