Emerging targets in neuroinflammation-driven chronic pain

Abstract

Current analgesics predominately modulate pain transduction and transmission in neurons and have limited success in controlling disease progression. Accumulating evidence suggests that neuroinflammation, which is characterized by infiltration of immune cells, activation of glial cells and production of inflammatory mediators in the peripheral and central nervous system, has an important role in the induction and maintenance of chronic pain. This review focuses on emerging targets such as chemokines, proteases and the Wnt pathway that promote spinal cord neuroinflammation and chronic pain. It also highlights the anti-inflammatory and pro-resolution lipid mediators that act on immune cells, glial cells and neurons to resolve neuroinflammation, synaptic plasticity and pain. Targeting excessive neuroinflammation could offer new therapeutic opportunities for chronic pain and related neurological and psychiatric disorders.

CD11b+Ly6G−myeloid cells mediate mechanical inflammatory pain hypersensitivity

“…Cytokines and chemokines secreted by immune cells can change pain sensitivity, acting directly or indirectly on sensory neurons (28). We therefore used a multiplex cytokine assay to assess changes in the levels of these mediators in the two models.…”

Nociceptive neurons regulate innate and adaptive immunity and neuropathic pain through MyD88 adapter

“…Our data failed to support an activating role of nociceptive neuron-MyD88 in peripheral inflammation: both capsaicin-induced neurogenic inflammation and CFA-induced lymphadenopathy are intact in Myd88-CKO mice. Given the distinct roles of inflammation (in non-neuronal tissue) and neuroinflammation (in neural tissue) in the initiation and maintenance of chronic pain [15], we conclude that MyD88 in nociceptive neurons might sustain chronic pain by controlling neuroinflammation (infiltration of immune cells) in the PNS.…”

Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats

“…Consequently, there is a considerable need to explore novel treatment modalities [1]. Emerging evidence suggests that the peripheral and central neuroinflammation associated with the chemokine-cytokine network following nerve damage plays pivotal roles in the pathogenesis of neuropathic pain [2,3]. Thus, further investigation of the functions of the chemokinecytokine network-mediated regulation of neuroinflammation might lead to novel therapeutic strategies [4].…”