CXCR4 and Pain: Wilson et al. (2011) also suggested that sensory neurons sensitized by the CXCL12-CXCR4 axis (or the gp120-CXCR4 axis) may facilitate the hyperalgesia induced by opioids. Moreover, morphine induces CXCR4-mediated activation of extracellular signal-regulated kinase (ERK) in rat neurons, a crucial regulator of peripheral and central sensitization. This may be one mechanism of gp120/opioid synergism in neuropathic pain (Ji, 2004; Patel et al., 2006; Sengupta et al., 2009).