RT Journal Article SR Electronic T1 Crucial Role of CB2 Cannabinoid Receptor in the Regulation of Central Immune Responses during Neuropathic Pain JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 12125 OP 12135 DO 10.1523/JNEUROSCI.3400-08.2008 VO 28 IS 46 A1 Ildiko Racz A1 Xavier Nadal A1 Judith Alferink A1 Josep E. Baños A1 Jennifer Rehnelt A1 Miquel Martín A1 Belén Pintado A1 Alfonso Gutierrez-Adan A1 Elena Sanguino A1 Jorge Manzanares A1 Andreas Zimmer A1 Rafael Maldonado YR 2008 UL http://www.jneurosci.org/content/28/46/12125.abstract AB Neuropathic pain is a clinical manifestation of nerve injury difficult to treat even with potent analgesic compounds. Here, we used different lines of genetically modified mice to clarify the role played by CB2 cannabinoid receptors in the regulation of the central immune responses leading to the development of neuropathic pain. CB2 knock-out mice and wild-type littermates were exposed to sciatic nerve injury, and both genotypes developed a similar hyperalgesia and allodynia in the ipsilateral paw. Most strikingly, knock-outs also developed a contralateral mirror image pain, associated with an enhanced microglial and astrocytic expression in the contralateral spinal horn. In agreement, hyperalgesia, allodynia, and microglial and astrocytic activation induced by sciatic nerve injury were attenuated in transgenic mice overexpressing CB2 receptors. These results demonstrate the crucial role of CB2 cannabinoid receptor in modulating glial activation in response to nerve injury. The enhanced manifestations of neuropathic pain were replicated in irradiated wild-type mice reconstituted with bone marrow cells from CB2 knock-outs, thus demonstrating the implication of the CB2 receptor expressed in hematopoietic cells in the development of neuropathic pain at the spinal cord.