Analgesic Effects Of Nod1 And Nod2 Agonists

In this chapter, we have demonstrated analgesic activities of NOD1 as well as NOD2 agonists. Intravenous injection of NOD2-agonistic muramyldipeptide (MDP) and its derivatives, 6-O-stearoyl-MDP (L18-MDP) and MDP-Lys(L18), and NOD1-agonistic FK156 and FK565 exhibited analgesic activity in BALB/c mice. FK565 exhibited the analgesic activity by various administration routes: intraperitoneal, intramuscular, sublingual, subcutaneous, intragingival, intragastric, and intracerebroventricular. The analgesic effect of intravenously administered FK565 starts after 30 min and persists for 24 h, and is observed even in tumor necrosis factor (TNF)-alpha knock out (KO), interleukin (IL)-1 alpha/beta double KO, and triple KO mice. Naloxane, a nonselective antagonist for opioid-receptors, completely inhibited the analgesic effect of FK565. These findings suggest that NOD1 and NOD2 activation induces analgesic effect via opioid-receptor(s) in a TNF-alpha and IL-1 alpha/beta-independent manner.