CB1 cannabinoid receptors in amphibian spinal cord: relationships with some nociception markers

The role of cannabinoids in spinal analgesia has so far been investigated in mammals and the interactions between cannabinoid receptors and markers involved in nociception have been described in the rat spinal cord. An endocannabinoid system is well developed also in the amphibian brain. However, the anatomical substrates of pain modulation have been scarcely investigated in anamniotes, neither is there reference to such a role for cannabinoids in lower vertebrates. In the present paper we employed multiple cytochemical approaches to study the distribution of CB1 cannabinoid receptors and their morphofunctional relationships with some nociception markers (i.e. Substance P, nitric oxide synthase, GABA and μ opioid receptors) in the spinal cord of the anuran amphibian Xenopus laevis. We found a co-distribution of CB1 receptors with the aforementioned signaling molecules, as well as a more limited cellular co-localization, in the dorsal and central fields of the spinal cord. These regions correspond to the mammalian laminae I–IV and X, respectively, areas strongly involved in spinal analgesia. Comparison of these results with those previously obtained in the mammalian spinal cord, reveals a number of similarities between the two systems and suggests that cannabinoids might participate in the control of pain sensitivity also in the amphibian spinal cord.