Role of capsaicin sensitive sensory nerves in ischemia reperfusion-induced acute kidney injury in rats

Highlights: • The sensory neuropeptides of CGRP and SP significantly increased after renal IR injury in kidney. • The large dose of capsaicin treatment in neonatal rats resulted in degeneration of capsaicin sensitive sensory nerves. • The degeneration of capsaicin sensitive sensory nerves and the reduction of CGRP and SP aggravated IR-induced AKI in rats. • The degeneration of capsaicin sensitive sensory nerves activated the ERK signal pathway of spinal cord and kidney. Acute kidney injury (AKI) is a common kidney disorder which is associated with a high risk of mortality. Extensive evidence revealed the participation of renal afferent sensory nerves in the pathophysiology of renal ischemia reperfusion (IR) injury, however the role of these nerves in renal IR injury is controversial and remains to be further explored. Here, we report that capsaicin sensitive sensory nerves and neuropeptides prevented renal damage in AKI induced by IR injury. The sensory afferent degeneration model was established by injecting 50 mg/kg of capsaicin to male neonatal rats and verified by the tail flick test and reduced sensory neuropeptide of substance P and calcitonin gene related peptide in spinal cord, dorsal root ganglion and kidney after 12 weeks. Then, a model of renal IR injury was established. The sensory afferent degeneration in the AKI group increased the level of serum creatinine, NGAL and KIM-1, aggravated to some extent renal pathological damage, and enhanced the proinflammatory cytokines expressions and tubular cell apoptosis. In addition, it was also discovered that the level of phospho-ERK/ERK (p-ERK/ERK) showed an increase in spinal cord and kidney after degeneration of capsaicin sensitive sensory nerves. In conclusion, the degeneration of sensory nerves aggravated IR-induced AKI in rats, and the activated ERK signaling in spinal cord and kidney after sensory afferent degeneration might be the possible mechanism in the aggravated renal injury.