Preconditioning with hydrogen sulfide prevents bone cancer pain in rats through a proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway

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 H₂S may act as a neuroprotectant to protect against some diseases in central nervous system. The preset study aimed to investigate the antinociceptive effect of H₂S in BCP. We first measured the changes of serum H₂S in patients with BCP and analyzed the relationship between them, then investigated the effect of H₂S preconditioning on BCP, and explored the mechanism in rat model. Our results revealed that serum H₂S level was negatively correlated with pain scores. In the rat model of BCP, preconditioning with H₂S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. The mechanism of H₂S 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 H₂S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. Second, the mechanism of H₂S 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 H₂S and exogenous H₂S in the development of BCP and present us a new strategy of pain management.