The NOD2 signaling in peripheral macrophages contributes to neuropathic pain development

• Published in: Pain (Amsterdam) Vol. 160; no. 1; pp. 102 - 116
• Main Authors: Santa-Cecília, Flávia V, Ferreira, David W, Guimaraes, Rafaela M, Cecilio, Nerry T, Fonseca, Miriam M, Lopes, Alexandre H, Davoli-Ferreira, Marcela, Kusuda, Ricardo, Souza, Guilherme R, Nachbur, Ueli, Alves-Filho, José C, Teixeira, Mauro M, Zamboni, Dario S, Cunha, Fernando Q, Cunha, Thiago M
• Format: Journal Article
• Language: English
• Published: United States 01.01.2019
• Subjects: Animals; Bone Marrow Transplantation; Carrageenan - toxicity; Disease Models, Animal; Inflammation - chemically induced; Inflammation - therapy; Interleukin 1 Receptor Antagonist Protein - therapeutic use; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Minocycline - therapeutic use; Neuralgia - genetics; Neuralgia - pathology; Neuralgia - physiopathology; Neuralgia - surgery; Neuroprotective Agents - therapeutic use; Nod2 Signaling Adaptor Protein - genetics; Nod2 Signaling Adaptor Protein - metabolism; Receptor-Interacting Protein Serine-Threonine Kinase 2; Receptor-Interacting Protein Serine-Threonine Kinases - genetics; Receptor-Interacting Protein Serine-Threonine Kinases - metabolism; Receptors, Tumor Necrosis Factor, Type I - genetics; Receptors, Tumor Necrosis Factor, Type I - metabolism; RNA, Small Interfering - therapeutic use; Signal Transduction - genetics; Signal Transduction - physiology; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Xanthines - therapeutic use
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1097/j.pain.0000000000001383

Neuropathic pain is one of the most important types of chronic pain. It is caused by neuronal damage. Clinical and experimental studies suggest a critical role for neuroimmune interactions in the development of neuropathic pain. In this article, we have shown that the cytoplasmic receptor Nod-like receptor-2, NOD2, and its adaptor-signaling molecule RIPK2 participate in the development of neuropathic pain after peripheral nerve injury (spared nerve injury model). The activation of NOD2 signaling in peripheral macrophage mediates the development of neuropathic pain through the production of pronociceptive cytokines (tumor necrosis factor and IL-1β). This study found that peripheral nerve injury promoted a systemic increase in the NOD2 ligand. These results highlight a previously undetermined role for NOD2 signaling in the development of neuropathic pain, suggesting a new potential target for preventing neuropathic pain.