CCR5 inhibition reduces neuropathic pain, increases beneficial analgesia from opioids (better pain control at lower doses), and reduces drug addiction by inhibiting mesolimbic dopamine transmission.
Attenuation of rodent neuropathic pain by an orally active peptide, RAP-103, which potently blocks CCR2- and CCR5-mediated monocyte chemotaxis and inflammation
Chemokine Receptor Antagonists in Combination with Morphine as a Novel Strategy for Opioid Dose Reduction in Pain Management
we demonstrated that in addition to CCR2, CCR5 is also required for the development of neuropathic pain.
Chemokines, cytokines and substance use disorders
Although opioids are widely prescribed for pain, in many circumstances, they have only modest efficacy. Preclinical studies have shown that chemokines, immune mediators released during tissue injury and inflammation, can desensitize opioid receptors and block opioid analgesia by a process termed “heterologous desensitization.” The present studies tested the hypothesis that in evoked pain, certain chemokine receptor antagonists (CRAs), given with a submaximal dose of morphine, would result in enhanced morphine potency.
In the incisional pain assay, it was found that the combination of a single CRA, or of both CRAs, with morphine significantly shifted the morphine dose-response curve to the left, as much as 3.3-fold
In terms of opioids, antagonists of chemokine receptors, especially CXCR4 and CCR5, may act as bifunctional opioid modulators by 1) preventing μ-opioid receptor desensitization, thus enhancing and preserving analgesic efficacy, while 2) simultaneously reducing the abuse liability of opioids through inhibition of mesolimbic dopamine transmission.