PERIAQUEDUCTAL GREY (AKA PAG)

As you have been studying brain stem levels #9 and #10, I am certain that you have been wondering just what that area surrounding the cerebral aqueduct is. Well, surprisingly it is called the periaqueductal grey (or gray)! This is an interesting area that is involved the regulation of pain. It has been demonstrated that stimulation of this area in rats eliminates their perception of pain. This is called stimulation produced analgesia or SPA (or stimulation induced analgesia; SIA).

The pathway over which this pain reduction takes place is a projection from cells in the PAG to a serotonergic nucleus in the medulla called the nucleus raphe magnus (NRM). The NRM, which is not seen on your fiber-stained sections, lies right down the middle of the medulla and is thus called a raphe (Gr., zipper) nucleus. Cells in the NRM project to the dorsal horn along the entire length of the spinal cord and these axons inhibit the cell of origin of the anterolateral system (spinothalamic tract). Thus, when the PAG fires the NRM fires and the end result is a decrease in pain impulses traveling up the ALS to reach the VPL and somatosensory cortex, i.e., consciousness.

I know that you are wondering “what turns on this pain-reducing system.” Think back about the last time you were really mad at me for lecturing too long or calling on you (or waking you up!!) in front of your classmates. You were so upset that your “emotional brain” took over and caused you ignore your recently sprained ankle or newly acquired blister on your big toe (what dermatome is that???). What was happening is that pathways from your emotional brain (to be defined later) were exciting some cells in the PAG. The cells in the PAG that are turned on have receptors for opiate peptides called endorphins (enkephalins are one of the three groups of endorphins).



Since the cells in the PAG contain receptors for opiate peptides, systemic injections of morphine-like substances can reduce pain by turning on the smaller inhibitory PAG neurons in the midbrain.

Some of the pathways just discussed may underlie the results of classical acupuncture. Rotation of thin needles could stimulate the C and D fibers in body tissue and in turn the ALS. While you are thinking this should hurt, branches of ALS fibers (collaterals of those heading to the VPL) could end in the PAG (or NRM) and somehow turn on the descending pain modulation circuit. We do not understand the details of this circuit, but it is known that acupuncture is “opiate dependent.” That is, intravenous injection of naloxone (an opiate inhibitor) is thought to block the effects of acupuncture (and SPA and SIA).