Cannabinoids

Cannabinoid Mechanisms of Pain Suppression 513

Fig. 1.Schematic of neural pathways that process and modulate the transmission of information about
nociceptive signals. Inorange, the spinothalamic tract is shown, with signals originating in the peripheral
nerve, crossing the midline, and ascending the anterolateral white matter of the spinal cord with many
collateral outputs to the brainstem shown for the RVM and PAG. This tract terminates in the VPL/VPM
thalamus. Ingreen, descending pain inhibitory pathways are shown, which connect the PAG to the RVM,
and from there makes connections in the spinal cord. Other descending inhibitory pathways originating
in the LC and noradrenergic nucleus A5 are also shown. Inred, pathways that facilitate pain are shown
originating in the RVM and descending to the spinal cord. Abbreviations:A5, noradrenergic nucleus A5;D.
Facil., descending facilitation pathway;D. Inhib, descending inhibitory pathways;DRG, dorsal root ganglion;
LC, locus coeruleus;PAG, periaqueductal gray;RVM, rostral ventromedial medulla;STT, spinothalamic tract;
VPL, ventroposterolateral nucleus;VPM, ventral posteromedial nucleus

1.3

Descending Modulation of Pain

1.3.1

Descending Pain Inhibition

With the observation by Kang Tsou (Tsou and Jang 1964) of the potent analgesic
effects of morphine applied by microinjection to the periaqueductal gray came the
early realization that the brain plays an active role in determining whether pain
is felt following noxious stimulation. Later, it was observed by Reynolds (1969)
that electrical stimulation of this region in the rat produced sufficient analgesia
for a pain-free laparotomy without additional anesthesia. Akil et al. (1976) noted