An analgesic pathway from parvocellular oxytocin neurons to the periaqueductal gray in rats

Abstract

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 parvocellular OT axons in the vlPAG induced local OT release, as measured with OT sensor GRAB. In vivo, optogenetically-evoked 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.

Neural circuitry for maternal oxytocin release induced by infant cries

“…Parvocellular neurons project to the VTA 42 which is consistent with our results that the PIL to PVN pathway mediates pup call-induced oxytocin release in VTA and that blocking oxytocin signaling in the VTA impairs pup retrieval behavior. Even though parvocellular neurons may be only a small number of the total number of oxytocin cells within the PVN, they innervate an important amount of central areas and have been shown to mediate a wide variety of synaptic mechanisms, sensory processing and behaviors 1,4,14,51,52,53,54,55 . Parvocellular PVN cells have more complex morphology 53 and potentially innervate multiple brain areas by ramified collaterals 1,56 .…”

A Biomimetic C-Terminal Extension Strategy for Photocaging Amidated Neuropeptides

“…OT plays important roles in childbirth and lactation, social bonding, and sexual function. It also has analgesic effects in the brain and spinal cord. , Although several side chain-caged analogues of OT were reported recently, C-terminus caging has not been explored. SP contributes to the transmission of pain signals from the periphery to the central nervous system and to inflammation by promoting cytokine release.…”

Intertwined associations between oxytocin, immune system and major depressive disorder

“…Different measurements used in different studies may result in disparate results. With the advancement of OXT sensors, it will be possible to measure endogenous OXT levels in real time, accurately tracking OXT changes [65] , [66] . Second, OXT level is reported to differ between male and female, which may account for the mixed results observed in various studies.…”