Central administration of C-X-C chemokine receptor type 4 antagonist alleviates the development and maintenance of peripheral neuropathic pain in mice

Abstract

C-X-C chemokine receptor type 4 (CXCR4) is an emerging area of pain hypersensitivity in the peripheral nervous system; however, its role in the central nervous system (CNS) for pain processing remains unclear. This study aimed at exploring the function of central CXCR4 in pain processing in vivo using its specific antagonist AMD3100 and partial sciatic nerve ligation (pSNL) model of peripheral neuropathic pain in C57BL/6 mice. A single intrathecal (central) administration of AMD3100 (intrathecal AMD3100, 5 μg) was found to prevent the development of pSNL-induced allodynia. Intrathecal AMD3100 (1 μg, 5 μg and 25 μg) also reversed the established pSNL-induced mechanical allodynia in a dose-dependent way on post-operative day 7 (POD 7). In rotarod test, intrathecal AMD3100 of different dosages (1 μg, 5 μg and 25 μg) did not impair the motor function of mice. Among mitogen-activated protein kinases (MAPKs) pathways, intrathecal AMD3100 was found to downregulate the activation of JNK1 and p38 pathway signaling proteins in the L3-L5 spinal cord segment as assessed by western blotting on POD 7. Our results firstly suggest that central (spinal) CXCR4 appears to be involved in the development and maintenance of peripheral neuropathic pain, implicating that CXCR4 would potentially be a therapeutic target for chronic neuropathic pain.