Selective axonal and glial distribution of monoacylglycerol lipase immunoreactivity in the superficial spinal dorsal horn of rodents.

The importance of 2-AG-mediated endogenous cannabinoid signaling in spinal pain control has recently been well substantiated. Although the degradation of 2-AG seems to be essential in cannabinoid-mediated spinal nociceptive information processing, no experimental data are available about the cellular distribution of monoacylglycerol lipase (MGL), the main degrading enzyme of 2-AG in the spinal dorsal horn. Thus, here we investigated the cellular distribution of MGL in laminae I-II of the spinal gray matter with immunocytochemical methods and revealed an abundant immunoreactivity for MGL in the rodent superficial spinal dorsal horn. We addressed the co-localization of MGL with markers of peptidergic and non-peptidergic primary afferents, axon terminals of putative glutamatergic and GABAergic spinal neurons, as well as astrocytic and microglial profiles, and we found that nearly 17 % of the peptidergic (immunoreactive for CGRP), a bit more than 10 % of the axon terminals of putative glutamatergic spinal neurons (immunoreactive for VGLUT2), and approximately 20 % of the astrocytic (immunoreactive for GFAP) profiles were immunolabeled for MGL. On the other hand, however, axon terminals of non-peptidergic (binding isolectin-B4) nociceptive primary afferents and putative inhibitory spinal neurons (immunoreactive for VGAT) as well as microglial (immunoreactive for CD11b) profiles showed negligible immunostaining for MGL. The results suggest that only nociceptive inputs arriving through a population of CGRP immunoreactive fibers are modulated by the spinal DGLα-MGL pathway. We also postulate that the DGLα-MGL signaling pathway may modulate spinal excitatory but not inhibitory neural circuits.