Cannabinoid Mechanisms of Pain Suppression 517because the splice variant bears a truncated N terminus (Salio et al. 2002b). How-
ever, it is unclear whether these isoforms are differentially distributed in the spinal
dorsal horn. This review will compare the distribution of CB1R mRNA and CB1R
immunoreactivity in rat dorsal root ganglion cells. The distribution of CBRs in
rat spinal cord revealed by receptor binding and quantitative autoradiography will
subsequently be compared with patterns of CB1R immunostaining revealed by
immunocytochemistry using antibodies recognizing different epitopes of CB1R.
3.2
Antinociception Mediated by CB1Rs in the Periphery
The distribution of CBRs outside the central nervous system is consistent with
behavioral and neurochemical data that implicate a role for peripheral CB1Rs in
cannabinoid antinociception. The distribution of CB1Rs in dorsal root ganglia
and peripheral nerve is therefore reviewed here. The role of CB2Rs in cannabinoid
antinociceptive mechanisms is reviewed in Sect. 4.
Traditionally, the dorsal root ganglion (DRG) has been used as a model of the
peripheral nerve because of its more convenient size, location, and the ability
to correlate cell size and neurochemical phenotype with peripheral axon caliber.
Hohmann and Herkenham (1999a,b) used in situ hybridization to test the hypoth-
esis that dorsal root ganglion cells, the source of primary afferent input to the
Fig. 3.Distribution of cannabinoid CB 1 receptor (CB1R) mRNA in rat (A) dorsal root ganglia and (B)brain.
Cannabinoid binding sites accumulate proximal to a tight ligation of the sciatic nerve. [^3 H]CP55,940 binding
and high-resolution emulsion autoradiography was used to demonstrate flow of cannabinoid receptors to
the periphery. Dark-field photomicrographs show damming of cannabinoid receptors proximal as opposed to
distal to (C) a single tight ligation and (D) the more proximal of two separate ligatures applied to the sciatic
nerve.Scale bars= 1 mm. (From Hohmann and Herkenham 1999a)