Spontaneous action potential activity in isolated dorsal root ganglion neurons from rats with a painful neuropathy

Abstract

One of the physiological changes accompanying neuropathic pain from nerve injury is the spontaneous firing of primary afferent fibers. At least some of this activity is thought to arise from the dorsal root ganglion. We have investigated whether this activity is resident in the cell bodies of dorsal root ganglion neurons and if it is retained in vitro. Dorsal root ganglion neurons from rats with a chronic constriction injury (CCI) from 4 loose ligatures of chromic gut sutures around the sciatic nerve were used. Isolated neurons were studied using the whole cell patch technique in current clamp mode within 6 hours of preparation. Neurons from rats with CCI showed a significantly increased incidence of spontaneous action potential activity (18/88 vs. 1/36 neurons). Firing activity consisted of both random spikes and long trains of regular, rapid spikes, with random activity being the exclusive mode in most cells. Spontaneous resting potential fluctuations (up to 10 m V peak-to-peak) occurred in both control and CCI neurons, and triggered the spontaneous, random action potentials in neurons from CCI rats. Spontaneously firing neurons exhibited more negative action potential threshold (-34.8 mV) when compared to quiescent neurons from ganglia either after CCI (-18.7 mV) or controls (-20.5 mV). These findings show that spontaneous action potential activity after CCI is a property residing in the cell bodies of dorsal root ganglion neurons and is amenable to more detailed analysis using such an in vitro system, allowing better understanding of the cellular changes underlying neuropathic pain from nerve injury.