The role of high-threshold calcium channels in spinal neuron hyperexcitability induced by knee inflammation

Abstract

This chapter discusses the neurobiology of voltage-dependent calcium channels (VDCCs) and summarizes the involvement of VDCCs in the spinal processing of nociceptive input from normal and inflamed knee joint. Neuronal VDCCs is subdivided on the basis of their electrophysiological and pharmacological properties into low voltage-activated or T-type channels and high voltage-activated (HVA) channels, a class that includes L-, N-, P/Q- and R-type channels. In general, L-type VDCCs are localized predominantly in the somata and proximal dendrites of neurons throughout the brain. N-type and P/Q-type VDCCs are localized in presynaptic terminals and dendritic shafts of neurons. To study the involvement of N-, P/Q-, and L-type VDCCs in the spinal processing of articular input, recordings were made from nociceptive neurons in the dorsal horn of anesthetized rats. VDCC blockers were administered topically onto the spinal cord at specific concentrations. The chapter discusses the effects of N-type, P/Q-type, and L-type channel antagonists on the responses of spinal cord neurons with input from the normal or inflamed knee joint. Effects of N-type and P/Q-type channel antagonists on the generation of inflammation-induced hyperexcitability of spinal cord neurons with input from the knee joint is also discussed.