Electrophysiological characterization of primary cilium ionic currents of dorsal root ganglia neurons upon inflammatory stimulation and their modulation by crotalphine

Abstract

Chronic pain affects around 30 % of the world's population. Treatment for this condition is still a challenge, becoming interesting the study of new drugs and new molecular targets capable to modulate the nociceptive system. Crotalphine is a synthetic peptide (patent PI 0502399-8 granted 05/05/2018) originally isolated from the South American Crotalus durissus terrificus snake venom, which has long-lasting analgesic action in acute and chronic pain models. However, its cellular/molecular target as well as its mechanism of action in peripheral neurons remains unclear. It is known that most cells, including neurons, have on their surface a cellular "nano-antenna" organelle called primary cilium with sensory functions. It is known that this organelle has an important role in Wnt signaling pathway that can, in turn, modulates calcium influx. However, the function of primary cilia in mammalian peripheral nervous system neurons as well as its role in nociceptive pathways is not known. Since crotalphine modulates the Wnt signaling upon chronic inflammatory stimulation, the aim of this work is to evaluate the electrophysiology of primary afferent neurons' primary cilia upon inflammatory stimulation and the role of crotalphine in this dynamic. In this way, the results of this project may open new perspectives on the mechanisms of action of crotalphine, as well as assigning the primary cilium an unprecedented cellular target to control the depolarization rate of peripheral neurons under inflammatory conditions. (AU)