Figure 2.

Involvement of chemokines and chemokine receptors in opioid-induced analgesia in NP. (A) Neuropathic pain conditions increase the production and release of a myriad of chemokines, whose binding to their specific receptors on neurons, astrocytes, and microglia decreases the nociceptive pain threshold and increases glial activation. Additionally, chronic μ-agonists administration further increases the chemokines and chemokine receptor expression and enhances the astrocyte and microglia reactivity in CNS. The neuronal activation of chemokine receptors by their specific ligands is followed by complex biochemical events that lead to heterodimer formation or heterologous desensitization between chemokine and opioid receptors, which lead to neuronal sensitization and reduce the opioid-induced analgesia. (B) The administration of chemokine-neutralizing specific antibodies or chemokine receptor specific antagonists reduces pain-related behaviors and glial cells activation and improve opioid efficacy in neuropathic conditions.