Somata of nerve-injured sensory neurons exhibit enhanced responses to inflammatory mediators

Abstract

The effects of inflammatory mediators in modulating the activity of nerve-injured dorsal root ganglion (DRG) neurons were studied in rats in an in vitro nerve-DRG preparation 2–4 weeks after a loose ligation of the sciatic nerve (chronic constriction injury, CCI). An inflammatory soup (IS) of bradykinin, serotonin, prostaglandin E 2 and histamine (each 10 −5 M, pH=7.4) was applied topically to the DRG. Evoked responses were recorded extracellularly from teased dorsal root fibers or intracellularly with sharp electrodes from somata of DRG neurons with myelinated (Aβ and Aδ) or unmyelinated (C) axons. IS increased the rate of ongoing spontaneous activity recorded from dorsal root fibers of CCI neurons and evoked activity in a subpopulation of previously ‘silent’ fibers in CCI rats but not those of unoperated controls. In comparison with DRG somata of control rats, those of CCI become more excitable as evidenced by a lower threshold to depolarizing current and a greater depolarization in response to IS. Inflammatory mediators, by increasing the excitability of DRG neurons, may contribute to paresthesiae, pain and hyperalgesia after peripheral nerve injury.