Lysozyme elicits pain during nerve injury by neuronal Toll-like receptor 4 activation and has therapeutic potential in neuropathic pain

Science Translational Medicine
Saurabh Yadav, Avadhesha Surolia

Abstract

The role of neuronal Toll-like receptor 4 (TLR4) in nerve injury is being pursued actively. However, the endogenous activation of neuronal TLR4 during neuroinflammation, in absence of the participation of glial TLR4, remains elusive. Here, we identified lysozyme as an endogenous activator of neuronal TLR4 signaling during nerve injury. Upon nerve injury, enhanced expression of lysozyme promoted neuronal hyperexcitability and neuropathic pain. Injections of lysozyme in healthy rats increased their mechanical and thermal pain sensitivity. Likewise, infusion of spinal cord slices with lysozyme increased neuronal excitability typical of neuropathic pain. Our results also showed that lysozyme activated excitability of both Aδ- and C-fibers. Thus, in addition to the discovery of lysozyme as an endogenous ligand for regulating neuronal TLR4 signaling, this study also lays the foundation of our understanding of its role in nervous system pathologies, providing multiple avenues for treating neuroinflammation.

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Citations

Apr 2, 2020·Investigative Ophthalmology & Visual Science·Abdelrahman Y FoudaRuth B Caldwell
Jul 14, 2020·Frontiers in Neuroscience·Helena F FilippiniBarry J Sessle
May 26, 2020·Pharmacology & Therapeutics·Bao-Chun JiangYong-Jing Gao
Jun 4, 2021·Frontiers in Neuroscience·Seung Won Lee, Hee Chul Han
Aug 5, 2021·Signal Transduction and Targeted Therapy·Danyang Li, Minghua Wu

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