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.