Abnormal spontaneous activity and responses to norepinephrine in dissociated dorsal root ganglion cells after chronic nerve constriction

Abstract

As part of ongoing studies of the cellular mechanisms of sympathetically maintained pain, we investigated the effects of a peripheral nerve injury on the responses of dissociated dorsal root ganglion (DRG) cells to norepinephrine (NE). Whole-cell patch-clamp recordings under current clamp were obtained from L4 and L5 DRG cells from adult rats in acute culture 11–25 days after a loose or tight ligation of the sciatic nerve. Only small to medium-sized cells from normal (uninjured) nerves and from loosely ligated nerves were tested with NE. One of 15 cells obtained from uninjured nerves responded to NE (500 μM, the highest dose, elicited a small depolarization without action potentials). In contrast, many cells from injured nerves responded to NE with a membrane depolarization, accompanied in some cases by the generation of action potentials. Fifty-two percent responded to 500 μM, while a significantly lower percentage responded to the lower doses of 100 μM (26%) and 10 μM (14%). Cells responsive to NE also responded to capsaicin. Spontaneous activity was observed in 14% and 21% of cells from loosely and tightly ligated nerves, respectively, but none of the cells from uninjured nerves. We conclude that the abnormal electrogenesis and responsiveness to NE in certain nerve-injured primary sensory neurons are due at least in part to changes in the membrane properties of the soma.