The neuronal distribution of cannabinoid receptor type 1 in the trigeminal ganglion of the rat

Abstract

Cannabinoid compounds have been shown to produce antinociception and antihyperalgesia by acting upon cannabinoid receptors located in both the CNS and the periphery. A potential mechanism by which cannabinoids could inhibit nociception in the periphery is the activation of cannabinoid receptors located on one or more classes of primary nociceptive neurons. To address this hypothesis, we evaluated the neuronal distribution of cannabinoid receptor type 1 (CB1) in the trigeminal ganglion (TG) of the adult rat through combined in situ hybridization (ISH) and immunohistochemistry (IHC). CB1 receptor mRNA was localized mainly to medium and large diameter neurons of the maxillary and mandibular branches of the TG. Consistent with this distribution, in a de facto nociceptive sensory neuron population that exhibited vanilloid receptor type 1 immunoreactivity, colocalization with CB1 mRNA was also sparse (<5%). Furthermore, very few neurons (approximately 5%) in the peptidergic (defined as calcitonin gene-related peptide-or substance P-immunoreactive) or the isolectin B 4 -binding sensory neuron populations contained CB1 mRNA. In contrast, and consistent with the neuron-size distribution for CB1, nearly 75% of CB1-positive neurons exhibited N52-immunoreactivity, a marker of myelinated axons. These results indicate that in the rat TG, CB1 receptors are expressed predominantly in neurons that are not thought to subserve nociceptive neurotransmission in the noninjured animal. Taken together with the absence of an above background in situ signal for CB2 mRNA in TG neurons, these findings suggest that the peripherally mediated antinociceptive effects of cannabinoids may involve either as yet unidentified receptors or interaction with afferent neuron populations that normally subserve non-nociceptive functions. Keywordscalcitonin gene-related peptide; vanilloid receptor type 1; substance P; isolectin B 4 ; in situ hybridizationThe primary psychoactive component of Cannabis sativa, Δ 9 -tetrahydrocannabinol, has long been recognized for its medicinal properties. Over the last two decades, a large body of work has elucidated the receptor-mediated actions of natural and synthetic cannabinoid compounds (for review, see Khanolkar et al., 2000). Two G protein-coupled cannabinoid receptors have been cloned, the cannabinoid receptor type 1 (CB1; Matsuda et al., 1990), found primarily in neurons, and the cannabinoid receptor type 2 (CB2; Munro et al., 1993) (Felder et al., 1993), as well as the modulation of neurotransmitter release through the inhibition of calcium currents (Twitchell et al., 1997;Shen and Thayer, 1998) and the activation of G protein-coupled inwardly-rectifying potassium channels (Mackie et al., 1995). On a whole organism level, endogenous cannabinoids as well as exogenously administered cannabinoids have been shown to, among other things, alleviate pain and inflammation.While there is ample evidence for antinociceptive effects of cannabinoids in the CNS (Lichtman and Martin, 1991;Martin et al., 1993Martin et ...

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“…This is because, under normal uninflamed conditions (with low peripheral NGF levels), the expression of CB 1 receptors on sensory neurons from DRG or trigeminal ganglia is predominantly on large-sized NF200-positive cells (Hohmann and Herkenham, 1999;Bridges et al, 2003;Price et al, 2003;Amaya et al, 2006). Consequently, extracellular AEA produced from FAAH-IR DRG neurons might be expected to signal at CB 1 receptors on separate cells.…”

The molecular logic of endocannabinoid signalling

“…Smaller numbers of CB 1 receptors are also found in the thalamus (especially in the anterior dorsal nucleus and habenula), hypothalamus (ventromedial and anterior nuclei), midbrain (periaqueductal grey and superior colliculus), medulla (dorsal vagal complex and rostral ventromedial medulla) and spinal cord (dorsal horn) 70,93 . Last, CB 1 is expressed in peripheral sensory neurons 98 , where it is localized in cells that express N52, a protein marker of mechanosensitive Aβ fibres 99 .…”

The RNA binding and transport proteins staufen and fragile X mental retardation protein are expressed by rat primary afferent neurons and localize to peripheral and central axons

“…Sense probes were used as a negative control, and no signal was observed with any of these probes. For isotopic ISH on human TG, obtained from the National Disease Research Interchange (Philadelphia, PA, USA), the procedure was identical to that described previously (Price et al, 2003). For ISH on rat DRG and TG images are representative of samples from three animals.…”