Background and aims: Recent experimental and clinical studies provide evidence for important role of chemokine receptors CCR2 and CCR5 in neuropathic pain pathomechanism. The aim was to compare the behavioural and molecular effects of maraviroc (CCR5 antagonist), RS504393 (CCR2 antagonist) and cenicriviroc (dual CCR2/CCR5 antagonist) and determine if the simultaneous blockade of both CCR2 and CCR5 is better than blocking only one of these receptors.

Methods: Wistar rats and Swiss Albino mice were subjected to chronic constriction injury (CCI) of sciatic nerve. Examined substances were injected intrathecally, repeatedly, and preemptively, then once per day for 7 days (rats) or once 9 days after CCI (mice). The neuropathic pain-related symptoms were assessed by von Frey and cold plate tests. The RT-qPCR was used for biochemical analysis. Significant difference were evaluated using ANOVA with Bonferroni correction. 

Results: The repeated administration of each of examined substances attenuated neuropathic pain in rats after CCI. It was correlated with reduction in spinal microglial activation. We observed that maraviroc reduced CCI-elevated level of pronociceptive CCL3-4. Cenicriviroc significantly lowered the spinal level of CCL2-4, and CCL7. In contrast, RS504393 did not influence the mRNA level of any of them. Finally, we demonstrated that single injection of cenicriviroc was the most effective in CCI-exposed mice.

Conclusion: Based on our results we suggest that blocking CCR2/CCR5 simultaneously brings more beneficial effects on both behavioral and molecular level. 

Acknowledgments: Supported by National Science Centre Poland grants: OPUS-2016/21/B/NZ4/00128, PRELUDIUM-2018/29/N/NZ7/00287 and statutory funds of Institute of Pharmacology, Polish Academy of Sciences.

COMPARISON OF ANALGESIC EFFECTS OF MARAVIROC, RS504393 AND CENICRIVIROC IN RODENTS AFTER SCIATIC NERVE INJURY BASED ON BEHAVIORAL AND MOLECULAR STUDIES