NOD2 and neuropathic pain: We also found that peripheral nerve injury can promote a systemic increase of an undetermined stimulant of NOD2 signaling.188 Thus, it is possible that after peripheral nerve injury gut microbiota–derived PAMPs (TLRs and NOD2 ligand; eg, lipopolysaccharides, peptidoglycan, and/or methylene diphosphonate) may translocate from the luminal side of the gut into the blood to distal sites (eg, sensory ganglia), activates PRRs signaling in sNAMs, and consequently contribute to the development of neuropathic pain.