muramidase and Neuralgia

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.

Topics: Animals; Annexin A2; Cell Membrane; Disease Models, Animal; Female; Ganglia, Spinal; Humans; Injections; Kinetics; Muramidase; Nerve Tissue; Neuralgia; Neurons; Nociceptors; Protein Binding; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries; Toll-Like Receptor 4; Up-Regulation

Novel pain killers without adverse effects are urgently needed. Opioids induce central and intestinal side effects such as respiratory depression, sedation, addiction, and constipation. We have recently shown that a newly designed agonist with a reduced acid dissociation constant (pK

Topics: Analgesics; Animals; Dose-Response Relationship, Drug; Drug Design; Hydrogen-Ion Concentration; Male; Molecular Structure; Muramidase; Neuralgia; Pain, Postoperative; Peptide Fragments; Rats; Rats, Wistar; Receptors, Opioid, mu