In Vivo Dissection of Two Intracellular Pathways Involved in the Spinal Oxytocin-Induced Antinociception in the Rat
Por:
Espinosa De los Monteros-Zuniga, Antonio, Martinez-Lorenzana, Guadalupe, Condes-Lara, Miguel, Gonzalez-Hernandez, Abimael
Publicada:
18 ago 2021
Resumen:
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.
Filiaciones:
Espinosa De los Monteros-Zuniga, Antonio:
Gonzalez-Hernandez, A (Corresponding Author), Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Desarrollo & Neurofisiol, Queretaro 76230, Qro, Mexico. Espinosa De los Monteros-Zuniga, Antonio
Martinez-Lorenzana, Guadalupe:
Gonzalez-Hernandez, A (Corresponding Author), Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Desarrollo & Neurofisiol, Queretaro 76230, Qro, Mexico. Espinosa De los Monteros-Zuniga, Antonio
Condes-Lara, Miguel:
Gonzalez-Hernandez, A (Corresponding Author), Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Desarrollo & Neurofisiol, Queretaro 76230, Qro, Mexico. Espinosa De los Monteros-Zuniga, Antonio
Gonzalez-Hernandez, Abimael:
Gonzalez-Hernandez, A (Corresponding Author), Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Desarrollo & Neurofisiol, Queretaro 76230, Qro, Mexico. Espinosa De los Monteros-Zuniga, Antonio
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