Role of Peripheral Immune Cells for Development and Recovery of Chronic Pain

Abstract

Chronic neuropathic pain (CNP) is caused by a lesion or disease of the somatosensory nervous system. It affects ~8% of the general population and negatively impacts a person's level of functioning and quality of life. Its resistance to available pain therapies makes CNP a major unmet medical need. Immune cells have been shown to play a role for development, maintenance and recovery of CNP and therefore are attractive targets for novel pain therapies. In particular, in neuropathic mice and humans, microglia are activated in the dorsal horn and peripheral immune cells infiltrate the nervous system to promote chronic neuroinflammation and contribute to the initiation and progression of CNP. Importantly, immunity not only controls pain development and maintenance, but is also essential for pain resolution. In particular, regulatory T cells, a subpopulation of T lymphocytes with immune regulatory function, and macrophages were shown to be important contributors to pain recovery. In this review we summarize the interactions of the peripheral immune system with the nervous system and outline their contribution to the development and recovery of pain.

Keywords: T cells; Tregs; chronic neuropathic pain; immune cells; macrophages; recovery.

Figure 1

Contribution of different immune cells to pain development and recovery. CD4⁺ T helper cells were shown to infiltrate the spinal cord, DRG and injured nerve, where they contribute to pain responses through different mechanisms. Further, DRG invading macrophages were shown to be important mediators of pain. Like T effector cells, Tregs infiltrate the nerve, DRG, and spinal cord in neuropathic mice and contribute to immunomodulation and tissue regeneration through different mechanisms, including secretion of anti-inflammatory IL-10. M2 macrophages were shown to initiate analgesic responses in the nerve through upregulation of the endogenous opioid system and anti-inflammatory responses.