Contribution of TRESK two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats

• Published in: Molecular pain Vol. 17; p. 17448069211023230
• Main Authors: Liu, Jiang-Ping, Jing, Hong-Bo, Xi, Ke, Zhang, Zi-Xian, Jin, Zi-Run, Cai, Si-Qing, Tian, Yue, Cai, Jie, Xing, Guo-Gang
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 2021; Sage Publications Ltd
• Subjects: Analgesics; Animal models; Animals; Bone cancer; Bone Neoplasms - complications; Calcitonin gene-related peptide; Dorsal root ganglia; Fibers; Ganglia, Spinal; Innervation; Neurons; Pain; Pain - complications; Periosteum; Potassium; Potassium Channels; Rats; Rats, Sprague-Dawley; Skin; Tibia; Tumors; cancer-induced skeletal pain; DRG; TRESK; bone cancer pain; IB4; CGRP; cancer-induced cutaneous pain
• ISSN: 1744-8069; 1744-8069
• DOI: 10.1177/17448069211023230

Cancer-associated pain is debilitating. However, the mechanism underlying cancer-induced spontaneous pain and evoked pain remains unclear. Here, using behavioral tests with immunofluorescent staining, overexpression, and knockdown of TRESK methods, we found an extensive distribution of TRESK potassium channel on both CGRP+ and IB4+ nerve fibers in the hindpaw skin, on CGRP+ nerve fibers in the tibial periosteum which lacks IB4+ fibers innervation, and on CGRP+ and IB4+ dorsal root ganglion (DRG) neurons in rats. Moreover, we found a decreased expression of TRESK in the corresponding nerve fibers within the hindpaw skin, the tibial periosteum and the DRG neurons in bone cancer rats. Overexpression of TRESK in DRG neurons attenuated both cancer-induced spontaneous pain (partly reflect skeletal pain) and evoked pain (reflect cutaneous pain) in tumor-bearing rats, in which the relief of evoked pain is time delayed than spontaneous pain. In contrast, knockdown of TRESK in DRG neurons produced both spontaneous pain and evoked pain in naïve rats. These results suggested that the differential distribution and decreased expression of TRESK in the periosteum and skin, which is attributed to the lack of IB4+ fibers innervation within the periosteum of the tibia, probably contribute to the behavioral divergence of cancer-induced spontaneous pain and evoked pain in bone cancer rats. Thus, the assessment of spontaneous pain and evoked pain should be accomplished simultaneously when evaluating the effect of some novel analgesics in animal models. Also, this study provides solid evidence for the role of peripheral TRESK in both cancer-induced spontaneous pain and evoked cutaneous pain.