Intrinsic Homeostatic Plasticity in Mouse and Human Sensory Neurons

Abstract

In response to changes in activity induced by environmental cues, neurons in the central nervous system undergo homeostatic plasticity to sustain overall network function during abrupt changes in synaptic strengths. Homeostatic plasticity involves changes in synaptic scaling and regulation of intrinsic excitability. Increases in spontaneous firing and excitability of sensory neurons are evident in some forms of chronic pain in animal models and human patients. However, whether mechanisms of homeostatic plasticity are engaged in sensory neurons under normal conditions or altered after chronic pain is unknown. Here, we showed that sustained depolarization induced by 30mM KCl induces a compensatory decrease in the excitability in mouse and human sensory neurons. Moreover, voltage–gated sodium currents are robustly reduced in mouse sensory neurons contributing to the overall decrease in neuronal excitability. Decreased efficacy of these homeostatic mechanisms could potentially contribute to the development of the pathophysiology of chronic pain.

Exaptation and Evolutionary Adaptation in Nociceptor Mechanisms Driving Persistent Pain

“…Associated negative feedback loops, including inhibition of AC5/6 by Ca 2+ (Fig. 2b) and AKAP-scaffolded phosphodiesterases and phosphatases (not shown), are probably important in nociceptors for protecting against inappropriate or excessive hyperactivity and possible excitotoxicity [85,194,195].…”