Journal
ACS CHEMICAL NEUROSCIENCE
Volume 12, Issue 16, Pages 3140-3147Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.1c00471
Keywords
Analgesia; behavior; nociception; pain; oxytocin; spinal dorsal horn
Funding
- CONACyT [326999]
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Behavioral and electrophysiological data demonstrate that oxytocin inhibits pain transmission at the spinal level by activating OTRs, which can mediate two distinct intracellular pathways - Gq (PLC/NOS/GC/K-ATP(+)) or Gi proteins, leading to differential effects on early and late nociceptive responses.
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 Gq proteins, which induce a rise of intracellular Ca2+ by activating the phospholipase C (PLC). However, in vitro data showed that OTRs cause a plethora of intracellular events, some related to the activation of Gi proteins. Using a behavioral approach, we analyzed the main in vivo 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 pertussis toxin (G alpha(i/o) protein inhibitor) or gallein (G(beta gamma) subunit inhibitor). In contrast, the late oxytocin-induced behavioral analgesia was blocked by pertussis and gallein but not by U-73122. Since oxytocin's effects during the early phase were also antagonized by Nco-nitro-L-arginine methyl ester, ODQ, or glibenclamide (inhibitors of nitric oxide synthase [NOS], soluble guanylyl cyclase [GC], and K-ATP(+) channels, respectively), the role of two differential pathways elicited by oxytocin is supported. Hence, we showed in in vivo experiments that oxytocin recruits two differential spinal intracellular pathways mediated by Gq (PLC/NOS/GC/K-ATP(+)) or Gi proteins during a peripheral nociceptive stimulus.
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