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

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.

TRP channels and monoterpenes: Past and current leads on analgesic properties.

The activation of the transient receptor potential (TRP) channels expressed by sensory neurons is essential to the transduction of thermal and mechanical sensory information. In the setting of chronic inflammatory conditions, the activation of the melastatin family member 8 (TRPM8), the TRP vanilloid 1 (TRPV1), and the TRP ankyrin 1 (TRPA1) is correlated with pain hypersensitivity reactions. Monoterpenes, among which pulegone and menthol, a major class of phytocompounds present in essential oils of medicinal plants, are known modulators of those TRP channels activity. In the present review, we correlate the monoterpene content of plants with their historical therapeutic properties. We then describe how monoterpenes exert their anti-inflammatory and antihyperalgesia effects through modulation of TRP channels activity. Finally, we discuss the importance and the potential of characterizing new plant extracts and reassessing studied plant extracts for the development of ethnopharmacology-based innovative treatments for chronic pain. This review suggests that monoterpene solutions, based on composition from traditional healing herbs, offer an interesting avenue for the development of new phytotherapeutic treatments to alleviate chronic inflammatory pain conditions.

Viral vectors for opto-electrode recording and photometry-based imaging of oxytocin neurons in anesthetized and socially interacting rats.

Here, we present a step-by-step protocol to target, record, and manipulate the activity of oxytocin neurons in awake rats. The protocol includes a procedure to record the activity of oxytocin neurons from awake and socially interacting rats using opto-electrodes for simultaneous electrophysiological recording and virally based cell-type-specific opto-tagging with Channelrhodopsin 2. Furthermore, we illustrate a procedure for optically guided implantation of optic fiber and imaging of oxytocin neuron population activity expressing calcium indicator GCaMP6s with the fiber photometry technique. For complete details on the use and execution of this protocol, please refer to Tang et al., 2020.