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Papers of the Week

Papers: 15 Apr 2023 - 21 Apr 2023

Basic Science

Animal Studies, Genetics, Molecular/Cellular, Neurobiology

Neuropathic Pain

2023 Apr 18

J Clin Invest


Silencing miR-21-5p in sensory neurons reverses neuropathic allodynia via activation of TGFB-related pathway in macrophages.


Zeboudj L, Sideris-Lampretsas G, Silva R, Al-Mudaris S, Picco F, Fox S, Chambers D, Malcangio M


Neuropathic pain remains poorly managed by current therapies highlighting the need to improve our knowledge of chronic pain mechanisms. In neuropathic pain models, dorsal root ganglia (DRG) nociceptive neurons transfer miR-21 packaged in extracellular vesicles to macrophages that promote pro-inflammatory phenotype and contribute to allodynia. Here we show that miR-21 conditional deletion in DRG neurons was coupled with lack of up-regulation of CCL2 chemokine after nerve injury and reduced accumulation of CCR2-expressing macrophages, which showed TGFB-related pathway activation and acquired M2-like anti-nociceptive phenotype. Indeed, neuropathic allodynia was attenuated in cKO and restored by a TGFB receptor inhibitor (SB431542) administration. Since TGFBR2 and TGFB1 are known miR-21 targets, we suggest that miR-21 transfer from injured neurons to macrophages maintains a pro-inflammatory phenotype via suppression of such an anti-inflammatory pathway. These data support miR-21 inhibition as a possible approach to maintain polarization of DRG macrophages at M2-like state and attenuate neuropathic pain.