In an animal model of human neuropathic pain, a chronic compression of the dorsal root ganglion (CCD) in rat induces some cell bodies (somata) in the ganglion to become hyperexcitable, spontaneously active and responsive to inflammatory mediators (IMs), such as serotonin, bradykinin or prostaglandin. Little is known of the sensory, neurochemical and electrophysiological properties of these intact, hyperexcitable neurons. The questions addressed in this proposal focus on the hyperexcitability of CCD somata: What are their receptive-field properties and neurochemical content? How do action potentials, originating in the dorsal root ganglion (DRG) and modulated by IMs, affect the coding and transmission of peripheral sensory information? What changes in voltage-gated ionic currents contribute to the somal hyperexcitability and responses to IMs? We have developed a novel preparation that superfuses the dorsal root ganglion (DRG) in vivo, allowing us to record from functionally identified neurons and chemically modulate the excitability of their somata while stimulating their receptive fields. In other experiments, we will combine current- and voltage-clamp patch recording from dissociated somata to examine the contribution of hyperpolarization-activated cation current, and voltage-gated potassium and sodium currents to CCD-induced changes in excitability and responses to IMs. The results will provide novel insights into the cellular mechanisms of the enhanced neuronal excitability contributing to neuropathic and inflammatory pain and hyperalgesia. ? ?
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