The latest research highlights the role of
chemokine signaling pathways in the development of nerve injury-induced
pain. Recent studies have provided evidence for the involvement of CCR2 and CCR5 in the pathomechanism underlying neuropathy. Thus, the aim of our study was to compare the effects of a selective CCR2 antagonist (RS504393), selective CCR5 antagonist (
maraviroc) and dual CCR2/CCR5 antagonist (
cenicriviroc) and determine whether the simultaneous blockade of both receptors is better than blocking only one of them selectively. All experiments were performed using Wistar rats/Swiss albino mice subjected to chronic constriction injury (CCI) of the sciatic nerve. To assess
pain-related reactions, the von Frey and cold plate tests were used. The
mRNA analysis was performed using RT-qPCR. We demonstrated that repeated intrathecal administration of the examined antagonists attenuated
neuropathic pain in rats 7 days post-CCI.
mRNA analysis showed that RS504393 did not modulate the spinal expression of the examined
chemokines, whereas
maraviroc reduced the CCI-induced elevation of CCL4 level.
Cenicriviroc significantly lowered the spinal levels of CCL2-4 and CCL7. At the dorsal root ganglia, strong impacts of RS504393 and
cenicriviroc on
chemokine expression were observed; both reduced the CCI-induced elevation of CCL2-5 and CCL7 levels, whereas
maraviroc decreased only the CCL5 level. Importantly, we demonstrated that a single intrathecal/
intraperitoneal injection of
cenicriviroc had greater
analgesic properties than RS504393 or
maraviroc in neuropathic mice. Additionally, we demonstrated that
cenicriviroc enhanced
opioid-induced
analgesia. Based on our results, we suggest that targeting CCR2 and CCR5 simultaneously, is an interesting alternative for
neuropathic pain pharmacotherapy.