Crucial role of CB<inf>2</inf> cannabinoid receptor in the regulation of central immune responses during neuropathic pain

Ildiko Racz, Xavier Nadal, Judith Alferink, Josep E. Baños, Jennifer Rehnelt, Miquel Martín, Belén Pintado, Alfonso Gutierrez-Adan, Elena Sanguino, Jorge Manzanares, Andreas Zimmer, Rafael Maldonado

    Research output: Contribution to journalArticleResearchpeer-review

    141 Citations (Scopus)


    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. Copyright © 2008 Society for Neuroscience.
    Original languageEnglish
    Pages (from-to)12125-12135
    JournalJournal of Neuroscience
    Issue number46
    Publication statusPublished - 12 Nov 2008


    • Astrocytes
    • Bone marrow chimera
    • CB cannabinoid receptor 2
    • Microglia
    • Neuroinflammation
    • Neuropathic pain


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