Blockade of nociceptive inhibition of plasma extravasation by opioid stimulation of the periaqueductal gray and its interaction with vagus-induced inhibition in the rat.

We have previously shown that stimulation of cutaneous or visceral nociceptors suppresses inflammation measured as bradykinin-induced synovial plasma extravasation in the knee joint of the rat. This suppression occurs through the activation of a spinal as well as a supraspinal reflex pathway leading to activation of the adrenal medullae and probably the release of epinephrine. These nociceptive-neuroendocrine reflex pathways are tonically inhibited by activity in abdominal vagal afferents acting through an inhibitory descending pathway projecting through the dorsolateral funiculus (DLF) ipsilateral to the cutaneous afferent nociceptive input. Here we investigated whether the descending inhibitory pathway acted upon by vagal afferents is also modulated by the periaqueductal gray (PAG), similar to other bulbo-spinal pathways acting on spinal nociceptive transmission. Injection of morphine sulfate (10 nmol) in the ventrolateral PAG significantly inhibited the nociceptive-neuroendocrine reflex pathways, an effect that was significantly less after removal of vagal afferents (i.e. after release from tonic inhibition maintained by vagal afferents). Interruption of the DLF ipsilateral to the nociceptive input removed the inhibitory effect of vagal afferents and partly reduced the inhibition produced by morphine injected in the PAG. From these investigations we conclude that PAG-induced inhibition of the nociceptive-neuroendocrine reflex pathways is mediated through the DLF ipsilateral to the nociceptive input, involving the same descending inhibitory pathway that relays afferent vagal inhibition, and through other spinal and possibly supraspinal pathways.