Spontaneous impulse generation in normal and denervated dorsal root ganglia: sensitivity to alpha-adrenergic stimulation and hypoxia.

Previous experiments indicate that after peripheral nerve lesion, two sites of spontaneous ectopic impulse generation rapidly develop: the peripheral neuroma and the region of the dorsal root ganglion (DRG). In 30 adult Sprague-Dawley rats, microfilament recordings were made from either the dorsal root of L5 or the proximal sciatic nerve. The locus of the ectopic impulse generator, spontaneous firing patterns, and response to both adrenergic and hypoxic stimulation were observed in 200 spontaneously active isolated fibers. Results indicated that after sciatic transection the neuroma and the DRG behaved as independent sources of ectopic impulse generation. Spontaneous activity originating in the neuroma was responsive to adrenergic and hypoxic stimulation in 57% and 86% of fibers tested, respectively. Spontaneous activity originating in the DRG after chronic sciatic nerve transection demonstrated a response to adrenergic stimulation in 61% of fibers tested, and all fibers showed an increase in activity during hypoxic periods. Furthermore, after acute sciatic neurotomy in otherwise normal animals, spontaneous activity originating in the DRG could be recorded in a few fibers. Likewise, 48% of those fibers showed some response to topical or systemic epinephrine administration, and hypoxia produced some degree of excitation of firing in all fibers tested. Neither epinephrine administration nor hypoxic challenge produced excitation of firing in DRG neurons with intact receptive fields in normal animals. The pharmacology of adrenergic sensitivity of spontaneously active fibers from both the neuroma and the region of the DRG indicated alpha-adrenergic specificity. Furthermore, a number of fibers exhibiting spontaneous activity from both the region of the neuroma and the DRG showed either adrenergic or hypoxic sensitivity, but not both. Thus, the mechanisms of the largely excitatory actions of alpha-agonists and hypoxia on spontaneous discharges from these sites were felt to be different. These data indicate that adrenergic and/or hypoxic responsiveness is a property of (i) otherwise normal DRG neurons which demonstrate intrinsic spontaneous firing properties, (ii) neurons in chronically denervated ganglia which exhibit spontaneous activity, and (iii) some fibers within neuromas. Normal DRG neurons with intact receptive fields do not appear to increase their firing rate in response to either hypoxia or adrenergic stimulation. These findings may be relevant to the development of chronic pain in man following peripheral nerve injury.