Dissection of Two Intracellular Pathways Involved in the Spinal Oxytocin-Induced Antinociception in the Rat.

Behavioral and electrophysiological data show that at the spinal level, oxytocin inhibits pain transmission by activation of oxytocin receptors (OTRs). Canonically, OTRs are coupled to G proteins, which induce a rise of intracellular Ca by activating the phospholipase C (PLC). However, data showed that OTRs cause a plethora of intracellular events, some related to the activation of G proteins. Using a behavioral approach, we analyzed the main intracellular pathway elicited by spinal oxytocin during a peripheral inflammatory/persistent nociceptive stimulus. Intrathecal oxytocin reduces early (number of flinches) and late (mechanical allodynia) formalin-induced nociception, an effect abolished by the OTR antagonist (L-368,899). Furthermore, the antinociception observed during the early phase (acute inflammatory) was also reverted by U-73122 (PLC inhibitor) but not by toxin (Gα protein inhibitor) or gallein (G subunit inhibitor). In contrast, the late oxytocin-induced behavioral analgesia was blocked by and gallein but not by U-73122. Since oxytocin's effects during the early phase were also antagonized by ω-nitro-l-arginine methyl ester, ODQ, or glibenclamide (inhibitors of nitric oxide synthase [NOS], soluble guanylyl cyclase [GC], and K channels, respectively), the role of two differential pathways elicited by oxytocin is supported. Hence, we showed in experiments that oxytocin recruits two differential spinal intracellular pathways mediated by G (PLC/NOS/GC/K) or G proteins during a peripheral nociceptive stimulus.