IN-VITRO CHARACTERIZATION OF A PERIPHERAL AFFERENT PATHWAY OF THE RATAFTER CHRONIC SCIATIC-NERVE SECTION

1. We have studied the characteristics of the abnormal properties of d amaged myelinated fibers (conduction velocity > 2.0 m/s) after periphe ral nerve injury in a novel in vitro model of the rat sciatic nerve/do rsal root ganglion/dorsal root (1,4-5) preparation removed from contro l naive or sham-operated rats and animals that had received sciatic ne urectomy 12-24 days before the in vitro study. A total of 122-245 fila ments were recorded in each dorsal root. The proportion of A alpha,bet a and A delta fibers were not significantly different between control, sham-operated, and axotomized nerves. Spontaneous activity was record ed in 3.4% (A alpha,beta) and 4.6% (A delta) of fibers in comparison w ith 0.4% (A alpha,beta) and 0.3% (A delta) in naive controls. 2. A spo radic, irregular, low-frequency (<1 Hz) firing was seen in 26% of the fibers with spontaneous activity. Periodical (irregular) bursting patt ern was observed in 43% of spontaneously active fibers, whereas a rela tively stable, ongoing firing pattern (median frequency: 7.1 Hz) was d isplayed by 31% of active fibers. 3. Mechanosensitivity of the neuroma /peripheral nerve was displayed in preparations from lesioned [axotomi zed: 18.2% (A alpha,beta) and 14.1% (A delta), sham operated: 2% (A al pha,beta) and 0%(A delta)], but not control naive animals. There was n o correlation between the presence of spontaneous activity and mechano sensitivity in single fibers. 4. The principal site of spontaneous act ivity generation was the dorsal root ganglion. Transection of the peri pheral nerve (or removal of the neuroma), while recording from dorsal root filaments, produced a cessation of firing in 21% of fibers firing with ongoing discharge. The remaining active fibers continued firing until the DRG was removed. A sustained injury discharge was observed i n damaged fibers but not control, undamaged fibers from naive animals after acute peripheral nerve transection. 5. We present an in vitro mo del for the study of abnormal primary sensory activity in peripheral n europathy. Although our data are consistent with in vivo electrophysio logical findings in published reports, the proportion of damaged affer ent fibers displaying spontaneous activity was significantly lower und er in vitro conditions. This model may serve as a valuable tool for fu rther physiological and pharmacological studies of peripheral neuropat hy.