The chemokine CX3CL1/fractalkine interferes with the antinociceptive effect induced by opioid agonists in the periaqueductal grey of rats

Abstract

We have reported that there is heterologous interaction between the mu, delta or kappa opioid receptors and the receptors for the chemokines CCL5/RANTES or CXCL12/SDF-1 in the regulation of antinociception in rats. CX3CL1/fractalkine, a chemokine that exclusively binds to CX3CR1, has been found to affect morphine analgesia and tolerance in the spinal cord. The purpose of the present study was to see if the interaction between the chemokine CX3CL1/fractalkine receptor and mu, delta or kappa opioid receptors occurs in the periaqueductal grey (PAG) of adult male S-D rats. The cold-water tail-flick (CWT) test was used to measure antinociception. The results showed that intra-PAG injection of 100 ng CX3CL1/fractalkine 30 min before administration of 400 ng DAMGO, 100 ng DPDPE or 20 μg dynorphin significantly reduced the antinociception induced by each of these peptides. These results demonstrate that activation of the CX3CL1 receptor diminishes the effect of mu, delta and kappa opioid agonists on their receptors in the PAG of rats.

The Chemokine Receptor CX3CR1 Is Involved in the Neural Tropism and Malignant Behavior of Pancreatic Ductal Adenocarcinoma

“…Recent animal studies have reported that CX3CL1 is implicated in the development of neuropathic pain via involvement of the microglia expressing the CX3CR1 receptor (34,46,47). When the chemokine was infused intrathecally, it enhanced the nociceptive response and the effect was abrogated or decreased by anti-CX3CR1 antibodies (46).…”

Activation of P2X7 receptors in the midbrain periaqueductal gray of rats facilitates morphine tolerance

“…On the one hand, the increased proinflammatory cytokines can interact with the opioid receptors and promote morphine tolerance. Chen (Chen et al, 2007) found that activation of the CX3CL1/fractalkine receptor diminished the effect of mu, delta, and kappa opioid agonists on their receptors in the PAG of rats. On the other hand, proinflammatory cytokines can up-regulate P2X 7 receptor expression and increase sensitivity to extracellular ATP in morphine tolerant rats (Humphreys and Dubyak, 1998;Narcisse et al, 2005).…”

Exploring the Neuroimmunopharmacology of Opioids: An Integrative Review of Mechanisms of Central Immune Signaling and Their Implications for Opioid Analgesia

“…Administration of the chemokines CCL5 (binding to CCR1), CXCL12 (binding to CXCR4) (Szabo et al, 2002;Chen et al, 2007b), and CX3CL1 (binding to CX3CR1) (Chen et al, 2007a) into the periaqueductal gray area significantly attenuated acute opioid analgesia. In addition, electrophysiology studies in single neurons have reported decreased opioid action after exposure to CCL2, CCL3, CCL5, or CXCL8 chemokines (Zhang et al, 2004).…”