Curcumin promotes microglial M2 polarization and suppresses chronic constriction: Injury-induced neuropathic pain in a rat model of peripheral neuropathy

Chun-Ta Huang; Po-Heng Chen; Seu-Hwa Chen; June-Horng Lue; Yi-Ju Tsai

doi:10.1016/j.nut.2023.112004

Curcumin promotes microglial M2 polarization and suppresses chronic constriction: Injury-induced neuropathic pain in a rat model of peripheral neuropathy

Nutrition. 2023 May:109:112004. doi: 10.1016/j.nut.2023.112004. Epub 2023 Feb 14.

Authors

Chun-Ta Huang¹, Po-Heng Chen², Seu-Hwa Chen³, June-Horng Lue⁴, Yi-Ju Tsai⁵

Affiliations

¹ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
² Graduate Institute of Biomedical and Pharmaceutical Science, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
³ Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁴ Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁵ School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: 065735@mail.fju.edu.tw.

PMID: 36931068
DOI: 10.1016/j.nut.2023.112004

Abstract

Objectives: Glia (i.e., astrocyte and microglia) activation in the central nervous system plays a critical role in developing neuropathic pain. Microglia can be activated into proinflammatory (M1) and anti-inflammatory (M2) phenotypes. Switching microglial polarization from M1 to M2 phenotypes represents a novel therapeutic strategy for neuropathic pain. Curcumin has been widely used for its anti-inflammatory and immunomodulatory effects. This study investigated effects of curcumin on astrocyte activation and microglia polarization in the cuneate nucleus (CN) and development of neuropathic pain behavior after chronic constriction injury (CCI) of the median nerve.

Methods: Rats were fed with curcumin once daily at a dose of 40, 80, or 120 mg/kg 30 min before and until 7 d after median nerve CCI. Subsequently, mechanical allodynia and thermal hyperalgesia were evaluated using von Frey filaments and plantar tests, respectively. The levels of astrocyte marker, monoclonal glial fibrillary acidic protein; microglia marker, ionized calcium-binding adapter molecule 1; M1 marker, CD86; and M2 marker, CD206 in the cuneate nucleus were determined. Enzyme-linked immunosorbent assay was applied to measure cytokine concentrations.

Results: Curcumin administration dose-dependently reduced mechanical allodynia and thermal hyperalgesia and decreased monoclonal glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 immunoreactivity in the ipsilateral cuneate nucleus after CCI. On ultrastructural observation, curcumin treatment was associated with fewer features of activated astrocytes and microglia. Furthermore, CCI rats given curcumin exhibited a decline in CD86 immunoreactivity and proinflammatory cytokine levels but an increase in CD206 immunoreactivity and release of anti-inflammatory cytokines.

Conclusions: In our findings, curcumin switches microglial phenotypes from M1 to M2 by suppressing astrocytic activation, reducing proinflammatory cytokine release, promoting anti-inflammatory cytokine production, and contributing to relief of neuropathic pain.

Keywords: Astrocyte; Curcumin; M1 to M2 polarization; Microglia; Neuropathic pain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium / metabolism
Constriction
Curcumin* / metabolism
Curcumin* / pharmacology
Cytokines / metabolism
Glial Fibrillary Acidic Protein / metabolism
Glial Fibrillary Acidic Protein / pharmacology
Hyperalgesia / complications
Hyperalgesia / etiology
Microglia / metabolism
Neuralgia* / complications
Neuralgia* / etiology
Rats
Rats, Sprague-Dawley

Substances

Curcumin
Glial Fibrillary Acidic Protein
Calcium
Cytokines