Preconditioning with hydrogen sulfide prevents bone cancer pain in rats through a proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway. Issue 1 (January 2018)

• Record Type: Journal Article
• Authors: Zhuang, Li; Li, Ke; Wang, Gaowei; Shou, Tao; Gao, Chunlin; Mao, Yong; Bao, Mingliang; Zhao, Mingli
• Is Part Of: Experimental biology and medicine. Volume 243:Issue 1(2018)
• Page Start: 57
• Page End: 65
• Publication Date: 2018-01
• Subjects: Bone cancer pain -- hydrogen sulfide -- preconditioning -- microglia -- proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway -- inflammatory cytokines; Physiology -- Periodicals; Biology, Experimental -- Periodicals; Medicine, Experimental -- Periodicals; 610.72
• DOI: 10.1177/1535370217740859
• Languages: English
• ISSNs: 1535-3702

Abstract

Bone cancer pain (BCP) is a severe type of hyperpathic pain occurring with primary bone tumors or advanced cancers which metastasize to bones. BCP can detrimentally reduce quality of life and presents a challenge to modern medicine. Studies have shown that exogenous H2 S may act as a neuroprotectant to protect against some diseases in central nervous system. The preset study aimed to investigate the antinociceptive effect of H2 S in BCP. We first measured the changes of serum H2 S in patients with BCP and analyzed the relationship between them, then investigated the effect of H2 S preconditioning on BCP, and explored the mechanism in rat model. Our results revealed that serum H2 S level was negatively correlated with pain scores. In the rat model of BCP, preconditioning with H2 S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. The mechanism of H2 S preconditioning may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. Impact statement: Bone cancer pain (BCP) significantly decreases the life quality of patients or their life expectancy and causes a severe health burden to the society. However, as the exact mechanism of BCP is still poorly understood, no effective treatment has been developed yet. There are some pain medicines now, but they have some inevitable side effects. Additional therapeutic strategies are urgently needed. First, we revealed that preconditioning with H2 S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. Second, the mechanism of H2 S preconditioning was elucidated. It may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. This novel finding may significantly help us to understand the difference between the roles of endogenous H2 S and exogenous H2 S in the development of BCP and present us a new strategy of pain management.