The Roles of Chemokine CXCL13 in the Development of Bone Cancer Pain and the Regulation of Morphine Analgesia in Rats

• Published in: Neuroscience 2019-05, Vol.406, p.62-72
• Main Authors: Bu, Hui-Lian, Xia, Yu-Zhong, Liu, Pan-Mei, Guo, Hai-Ming, Yuan, Chang, Fan, Xiao-Chong, Huang, Chen, Wen, Yuan-Yuan, Kong, Cun-Long, Wang, Tao, Ma, Le-Tian, Li, Xin-Xin, Zhang, Hong-Wei, Zhang, Li-Rong, Ma, Min-Yu, Ai, Yan-Qiu, Zhang, Wei
• Format: Article
• Language: English
• Subjects: Analgesia - methods; Analgesics, Opioid - administration & dosage; Animals; Bone Neoplasms - drug therapy; Bone Neoplasms - metabolism; cancer pain; Cancer Pain - drug therapy; Cancer Pain - metabolism; Chemokine CXCL13 - administration & dosage; CXCL13; Double-Blind Method; Female; Injections, Spinal; morphine; Morphine - administration & dosage; Random Allocation; Rats; Rats, Sprague-Dawley; signaling pathways; siRNA; Spinal Cord - drug effects; Spinal Cord - metabolism
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2019.02.025

Chemokines are important regulators of immune, inflammatory, and neuronal responses in peripheral and central pain pathway. The aim of this study was to investigate whether chemokine (C-X-C motif) ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) involve in the development of bone cancer pain (BCP) and the regulation of morphine analgesia in rats. The change of pain behaviors in BCP rats were measured by testing paw withdrawal threshold (PWT). The levels of CXCL13, CXCR5 and signal pathway proteins (p-p38, p-ERK and p-AKT etc.) in the spinal cord were measured via western blots. The expression of CXCL13 and CXCR5 in spinal cord was increased in BCP rats. The BCP rats showed decrease of PWTs, which was relieved by CXCR5i. Intrathecally injection of murine recombinant CXCL13 (mrCXCL13) decreased the PWTs of BCP rats and opposed morphine-induced analgesia in BCP rats. In BCP rats, the signal pathway proteins (p38, ERK and AKT) in the spinal cord were activated. CXCL13 and morphine had contrary effect on the phosphorylation of these proteins. MrCXCL13 directly increased the levels of p-p38, p-ERK and p-AKT in BCP rats. However, morphine decreased the levels of these proteins in BCP rats. While blocking the activation of p-p38, p-ERK and p-AKT, morphine analgesia was enhanced. These results suggest CXCL13 participated in bone cancer pain and opposed morphine analgesia via p38, ERK and AKT pathways. It may be a target to enhance pain management in cancer pain patients. •CXCL13 participates in the development of bone cancer pain by activating p38, ERK and AKT signaling pathways in rats.•Increase of spinal CXCL13 opposes morphine analgesia in BCP rats.•CXCL13 and morphine play contrary roles in the activation of p38, ERK and AKT signaling pathways.