Abstract
Pain is a signal of inflammation that can be both protective and pathogenic. Macrophages, a significant component of the immune system, play an essential role in the occurrence and development of pain, particularly in neuroimmune communication. Macrophages exhibit two distinct phenotypes: pro-inflammatory M1-like and anti-inflammatory M2-like phenotypes. Sensory neurons can promote macrophages into the M1 phenotype to produce pro-inflammatory mediators to defend against infection while causing tissue damage and inducing pain. However, this can be inhibited by M2 macrophages, facilitated by sensory nerves, resulting in pain resolution. This article provides an overview of the interplay between sensory nerves and M1/M2 macrophages during the induction and resolution of pain.
Key words :M1/M2 macrophages, pain, sensory neuron, inflammation
Introduction
Inflammation is a protective response of the body to injury and infection, characterized by five cardinal signals: tumor (edema), calor (heat), dolor (pain), rubor (redness), and fuctio laesa (loss of function). Acute pain is one of these signals (1). However, pain can persist beyond the duration of the injury and become chronic (neuropathic pain), which can have detrimental effects and diminish the quality of life. After tissue injury and infection, immune cells, including macrophages, initiate communication with sensory neurons, leading to hyperalgesia (an increased pain response to noxious thermal and mechanical stimuli) and allodynia (an increased pain response to normally innocuous stimuli) in both the peripheral and central nervous systems (PNS and CNS) (2).
Macrophages have three primary functions during inflammation: phagocytosis, antigen presentation, and cytokine production (3). These cells exhibit tremendous plasticity and marked functional heterogeneity, with various phenotypes, including pro-inflammatory M1-like and anti-inflammatory M2-like phenotypes (4, 5). M1-like macrophages generate cytokines and chemokines to remove pathogens during infection and promote pain, while M2-like macrophages secrete growth factors that facilitate tissue repair and pain resolution. This phenomenon of the two different M1/M2 phenotypes is referred to as ’macrophage polarization’ (6). The interaction between neurons and macrophages is critical in both the induction and resolution of pain. Macrophages have the ability to activate and resolve inflammation, playing distinct roles in both the induction and resolution of pain.
In this review, we will discuss recent advances in our understanding of the mechanisms that underlie the role of M1/M2 macrophages in the induction and resolution of pain, with a specific focus on the relationship between macrophages, inflammation, and sensory nerves.