Neuromodulatory Effect of Kappa Opioid Receptor Activation on Spinal Network Activity

Abstract

Dynorphin is a potent anti-nociceptive neuropeptide ubiquitously expressed throughout the peripheral and central nervous system. Previous studies have shown that dynorphin is co-packaged and co-released with orexin, a pro-locomotory neuropeptide known to be involved in goal-directed movement. Why then is an inhibitory neuropeptide co-released with an excitatory pro-locomotory neuropeptide orexin, and what is its role? In this thesis, the expression of kappa opioid receptors (KOR) on motoneurons was demonstrated using RNAscope Assay. Consistent with the observation of other studies, my results show that KOR activation significantly reduced spontaneous network activity, increased motoneuron excitability, and increased presynaptic inhibition. These results suggest that dynorphin modulates the spinal motor network rather than inhibits it. This also explains why the co-release of orexin and dynorphin does not have an antagonistic effect. My work suggests that perinatally dynorphin can have potent effects on spinal cord networks. This raises the possibility that dynorphin release may contribute to the development and correct function of spinal cord motor networks.