In vitro characterization of a peripheral afferent pathway of the rat after chronic sciatic nerve section

Abstract

1. We have studied the characteristics of the abnormal properties of damaged myelinated fibers (conduction velocity > 2.0 m/ s) after peripheral nerve injury in a novel in vitro model of the rat sciatic nerve/dorsal root ganglion/dorsal root (L4-5) preparation removed from control naíve or sham-operated rats and animals that had received sciatic neurectomy 12-24 days before the in vitro study. A total of 122-245 filaments were recorded in each dorsal root. The proportion of A alpha, beta and A delta fibers were not significantly different between control, sham-operated, and axotomized nerves. Spontaneous activity was recorded in 3.4% (A alpha, beta) and 4.6% (A delta) of fibers in comparison with 0.4% (A alpha, beta) and 0.3% (A delta) in naíve controls. 2. A sporadic, irregular, low-frequency (< 1 Hz) firing was seen in 26% of the fibers with spontaneous activity. Periodical (irregular) bursting pattern was observed in 43% of spontaneously active fibers, whereas a relatively stable, ongoing firing pattern (median frequency: 7.1 Hz) was displayed by 31% of active fibers. 3. Mechanosensitivity of the neuroma/peripheral nerve was displayed in preparations from lesioned [axotomized: 18.2% (A alpha, beta) and 14.1% (A delta), sham operated: 2% (A alpha, beta) and 0% (A delta)], but not control naíve animals. There was no correlation between the presence of spontaneous activity and mechanosensitivity in single fibers. 4. The principal site of spontaneous activity generation was the dorsal root ganglion. Transection of the peripheral 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 in damaged fibers but not control, undamaged fibers from naíve animals after acute peripheral nerve transection. 5. We present an in vitro model for the study of abnormal primary sensory activity in peripheral neuropathy. Although our data are consistent with in vivo electrophysiological findings in published reports, the proportion of damaged afferent fibers displaying spontaneous activity was significantly lower under in vitro conditions. This model may serve as a valuable tool for further physiological and pharmacological studies of peripheral neuropathy.

The antipsychotic drug, fluphenazine, effectively reverses mechanical allodynia in rat models of neuropathic pain

“…The discharge patterns were similar to those recorded in vivo (Kajander and Bennett 1992;Xie et al 1995) and in vitro (Babbedge et al 1996), including nonbursting discharges with regular (n=9) or irregular (n=31) interspike intervals, and occasionally bursting discharges (n=5). The firing rates ranged from 2 to 37 spikes/second.…”

Long-Term Alteration of S-Type Potassium Current and Passive Membrane Properties inAplysiaSensory Neurons Following Axotomy

“…In the case of somatic sensory neurons in mammals (Abdulla and Smith 2001b;Gallego et al 1987; Gurtu and Smith 1988;Kim et al 1998;Liu et al 2000;Stebbing et al 1999;Zhang et al 1997) and in the mollusk, Aplysia (Ambron et al 1996;Bedi et al 1998;Clatworthy and Walters 1994;Gunstream et al 1995;Walters et al 1991), axon injury often produces persistent hyperexcitability of the soma as well as parts of the neuron close to the site of injury (Billy and Walters 1989;Dulin et al 1995). Nociceptive sensory neuron hyperexcitability in mammals is thought to contribute to hyperalgesia and neuropathic pain (Abdulla and Smith 2001b;Babbedge et al 1996;Kajander et al 1992;Na et al 2000;Study and Kral 1996;Wall and Devor 1983). In Aplysia, similar hyperexcitability of sensory neurons is produced by axotomy and by manipulations associated with learning and memory.…”

Perfusion of the Mechanically Compressed Lumbar Ganglion With Lidocaine Reduces Mechanical Hyperalgesia and Allodynia in the Rat

“…Although the mechanism of neuropathic pain following nerve/ganglion injury is unresolved, evidence suggests that somata of the DRG may become an important source of pain after an injury of the peripheral nerve (Devor and Obermayer 1984). When rat peripheral nerves or primary sensory neurons are injured, certain DRG neurons become hyperexcitable and may exhibit various patterns of abnormal ectopic discharge (Babbedge et al 1996;Burchiel 1984;Hu and Xing 1998;Kajander et al 1992;Wall and Devor 1983;Xie et al 1995;Zhang et al 1997bZhang et al , 1999. The ionic and cellular mechanisms of the increased excitability are not known, but accumulation of certain types of sodium channels at the injured site or the related DRGs may account for the changes in membrane properties of the DRG somata and thus contribute to the enhancement of neuronal excitability (Devor et al 1993;Rizzo et al 1995;Zhang et al 1997a).…”