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

Abstract

As a 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 microM, 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 microM, while a significantly lower percentage responded to the lower doses of 100 microM (26%) and 10 microM (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.