Trophic influence of the distal nerve segment on GABAA receptor expression in axotomized adult sensory neurons

The depolarizing action of γ-aminobutyric acid (GABA), or the GABA_A receptor agonist muscimol, on rat dorsal root (L4 and L5) fibers is attenuated following transection, but not crush, of the sciatic nerve (15). Following discrete nerve crush, axons actively regenerate and contact both the distal nerve segment and the peripheral target tissues. The aim of the present study was to distinguish between these two regions as possible sources of trophic support for retrograde maintenance of dorsal root GABA receptor sensitivity. A surgical procedure was employed to permit a delimited segment of axonal regeneration while prohibiting reestablishment of end organ innervation; the sciatic nerve was crushed and a ligature was placed 3 cm distal to the crush site. Under these conditions, the injury-induced decrement in the dorsal root GABA response, observed between 12 and 21 postoperative days, was significantly attenuated relative to that of ligated nerves, in which regeneration into the distal stump does not occur. The data suggest that nerve transection by ligation restricts trophic support for maintenance of GABA receptor expression in dorsal root ganglion (DRG) neurons. Furthermore, during regeneration the denervated distal nerve segment assumes a neurotrophic role in the maintenance of dorsal root GABA sensitivity, consistent with the hypothesis that growth factors derived from reactive Schwann cells may positively regulate the expression of receptors on axotomized sensory neurons.