PT  - JOURNAL ARTICLE
AU  - Ildiko Racz
AU  - Xavier Nadal
AU  - Judith Alferink
AU  - Josep E. Baños
AU  - Jennifer Rehnelt
AU  - Miquel Martín
AU  - Belén Pintado
AU  - Alfonso Gutierrez-Adan
AU  - Elena Sanguino
AU  - Jorge Manzanares
AU  - Andreas Zimmer
AU  - Rafael Maldonado
TI  - Crucial Role of CB<sub>2</sub> Cannabinoid Receptor in the Regulation of Central Immune Responses during Neuropathic Pain
AID  - 10.1523/JNEUROSCI.3400-08.2008
DP  - 2008 Nov 12
TA  - The Journal of Neuroscience
PG  - 12125--12135
VI  - 28
IP  - 46
4099  - http://www.jneurosci.org/content/28/46/12125.short
4100  - http://www.jneurosci.org/content/28/46/12125.full
SO  - J. Neurosci.2008 Nov 12; 28
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.