Peripheral drive in Aα/β-fiber neurons is altered in a rat model of osteoarthritis: changes in following frequency and recovery from inactivation

Abstract

Qi Wu, James L HenryDepartment of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, CanadaPurpose: To determine conduction fidelity of Aα/β-fiber low threshold mechanoreceptors in a model of osteoarthritis (OA).Methods: Four weeks after cutting the anterior cruciate ligament and removing the medial meniscus to induce the model, in vivo intracellular recordings were made in ipsilateral L4 dorsal root ganglion neurons. L4 dorsal roots were stimulated to determine the refractory interval and the maximum following frequency of the evoked action potential (AP). Neurons exhibited two types of response to paired pulse stimulation. Results: One type of response was characterized by fractionation of the evoked AP into an initial nonmyelinated-spike and a later larger-amplitude somatic-spike at shorter interstimulus intervals. The other type of response was characterized by an all-or-none AP, where the second evoked AP failed altogether at shorter interstimulus intervals. In OA versus control animals, the refractory interval measured in paired pulse testing was less in all low threshold mechanoreceptors. With train stimulation, the maximum rising rate of the nonmyelinated-spike was greater in OA nonmuscle spindle low threshold mechanoreceptors, possibly due to changes in fast kinetics of currents. Maximum following frequency in Pacinian and muscle spindle neurons was greater in model animals compared to controls. Train stimulation also induced an inactivation and fractionation of the AP in neurons that showed fractionation of the AP in paired pulse testing. However, with train stimulation this fractionation followed a different time course, suggesting more than one type of inactivation.Conclusion: The data suggest that joint damage can lead to changes in the fidelity of AP conduction of large diameter sensory neurons, muscle spindle neurons in particular, arising from articular and nonarticular tissues in OA animals compared to controls. These changes might influence peripheral drive of spinal excitability and plasticity, thus contributing to OA sensory abnormalities, including OA pain.Keywords: dorsal root ganglion, repetitive firing, peripheral drive, electrophysiology, conduction failure, adaptation