An analgesic pathway from parvocellular oxytocin neurons to the periaqueductal gray in rats
Résumé
The hypothalamic neuropeptide oxytocin (OT) exerts prominent analgesic
effects via central and peripheral action. However, the precise analgesic
pathways recruited by OT are largely elusive. Here we discovered a subset of
OT neurons whose projections preferentially terminate on OT receptor (OTR)-
expressing neurons in the ventrolateral periaqueductal gray (vlPAG). Using a
newly generated line of transgenic rats (OTR-IRES-Cre), we determined that
most of the vlPAG OTR expressing cells targeted by OT projections are
GABAergic. Ex vivo stimulation of parvocellularOT axons in the vlPAG induced
local OT release, as measured with OT sensor GRAB. In vivo, optogeneticallyevoked
axonal OT release in the vlPAG of as well as chemogenetic activation of
OTR vlPAG neurons resulted in a long-lasting increase of vlPAG neuronal
activity. This lead to an indirect suppression of sensory neuron activity in the
spinal cord and strong analgesia in both female and male rats. Altogether, we
describe an OT-vlPAG-spinal cord circuit that is critical for analgesia in both
inflammatory and neuropathic pain models.
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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