The role of the endocannabinoid 2-arachidonoylglycerol in the in vivo spinal oxytocin-induced antinociception in male rats
Por:
Salinas-Abarca, Ana B., Martinez-Lorenzana, Guadalupe, Condes-Lara, Miguel, Gonzalez-Hernandez, Abimael
Publicada:
1 may 2023
Ahead of Print:
1 mar 2023
Resumen:
Oxytocin receptor (OTR) activation at the spinal level produces
antinociception. Some data suggest that central OTR activation enhances
social interaction via an increase of endocannabinoids (eCB), but we do
not know if this could occur at the spinal level, modulating pain
transmission. Considering that oxytocin via OTR stimulates
diacylglycerol formation, a key intermediate in synthesizing
2-arachidonylglycerol (2-AG), an eCB molecule, we sought to test the
role of the eCB system on the spinal oxytocin-induced antinociception.
Behavioral and elec-trophysiological experiments were conducted in naive
and formalin-treated (to induce long-term mechanical hypersensitivity)
male Wistar rats. Intrathecal RHC 80267 injections, an inhibitor of the
enzyme diacylglycerol lipase (thus, decreasing 2-AG formation), produces
transient mechanical hypersensitivity, an effect unaltered by oxytocin
but reversed by gabapentin. Similarly, in in vivo extracellular
recordings of naive spinal wide dynamic range cells, juxtacellular
picoinjection of RHC 80267 increases the firing of nociceptive A8-,
C-fibers, and post-discharge, an effect unaltered by oxytocin.
Interestingly, in sensitized rats, oxytocin picoinjection reverses the
RHC 80627-induced hyperactivity of A8-fibers (but not C-or
post-discharge activity). In contrast, a sub-effective dose of JZL184 (a
monoacylglycerol lipase inhibitor, thus favoring 2-AG levels), which
does not have per se an antinociceptive effect in the formalin-induced
hypernociception, the oxytocin-induced antinociception is boos-ted.
Similarly, electrophysiological experiments suggest that juxtacellular
JZL184 diminishes the neuronal firing of nociceptive fibers, and
co-injection with oxytocin prolongs and enhances the antinociceptive
effect. These data may imply that 2-AG formation may play a role in the
spinal antinociception induced by oxytocin.
Filiaciones:
Salinas-Abarca, Ana B.:
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM Juriquilla, QRO, Querétaro, 76230, Mexico
Department of Neural and Pain Sciences, University of Maryland Baltimore, 650 W. Baltimore Street, Baltimore, MD 21201, United States
Univ Nacl Autonoma Mexico, Dept Neurobiol Desarrollo & Neurofisiol, Inst Neurobiol, Campus UNAM Juriquilla, Queretaro 76230, Qro, Mexico
Univ Maryland, Dept Neural & Pain Sci, 650 W Baltimore St, Baltimore, MD 21201 USA
Martinez-Lorenzana, Guadalupe:
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM Juriquilla, QRO, Querétaro, 76230, Mexico
Univ Nacl Autonoma Mexico, Dept Neurobiol Desarrollo & Neurofisiol, Inst Neurobiol, Campus UNAM Juriquilla, Queretaro 76230, Qro, Mexico
Condes-Lara, Miguel:
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM Juriquilla, QRO, Querétaro, 76230, Mexico
Univ Nacl Autonoma Mexico, Dept Neurobiol Desarrollo & Neurofisiol, Inst Neurobiol, Campus UNAM Juriquilla, Queretaro 76230, Qro, Mexico
Gonzalez-Hernandez, Abimael:
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM Juriquilla, QRO, Querétaro, 76230, Mexico
Univ Nacl Autonoma Mexico, Dept Neurobiol Desarrollo & Neurofisiol, Inst Neurobiol, Campus UNAM Juriquilla, Queretaro 76230, Qro, Mexico
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