Macrophage: A key player in neuropathic pain

Abstract

Research on the relationship between macrophages and neuropathic pain has flourished in the past two decades. It has long been believed that macrophages are strong immune effector cells that play well-established roles in tissue homeostasis and lesions, such as promoting the initiation and progression of tissue injury and improving wound healing and tissue remodeling in a variety of pathogenesis-related diseases. They are also heterogeneous and versatile cells that can switch phenotypically/functionally in response to the micro-environment signals. Apart from microglia (resident macrophages of both the spinal cord and brain), which are required for the neuropathic pain processing of the CNS, neuropathic pain signals in PNS are influenced by the interaction of tissue-resident macrophages and BM infiltrating macrophages with primary afferent neurons. And the current review looks at new evidence that suggests sexual dimorphism in neuropathic pain are caused by variations in the immune system, notably macrophages, rather than the neurological system.

Plain Language Summary

Neuropathic pain is defined by the International Association for the Study of Pain as pain triggered or caused by primary damage to or dysfunction of the nervous system. Following intensive research into the mechanisms of neuropathic pain, macrophages have been revealed to play an important role in pathologic pain following nerve injury. Macrophages dynamically monitor the microenvironment to maintain tissue homeostasis. Once a macrophage is exposed to a pathologic stimulus, it in turn alters its functional phenotype and interacts with nociceptors, leading to neuropathic pain. This review wants to delve into the biology of macrophages in the central and peripheral nervous system, how they are related to play a role in neuropathic pain and whether there is sexual dimorphism in macrophages.

Graphical Abstract

Keywords:

• Central nervous system
• macrophage
• neuropathic pain
• peripheral nervous system
• sexual dimorphism

Authors’ contributions

JT, LDZ: Conceptualization. JT: Funding acquisition. YY, HC, YW: Writing—Original Draft. YS: Writing—Review & Editing. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by National Natural Science Foundation of China (81600975) and Scientific Research Project of Jiangsu Provincial Health commission (M2022081). Illustrations were created using BioRender.