Fig. 5. Light micrograph of rat sciatic nerve injected with amitriptyline alone (  A ) or coadministered with p38 mitogen-activated protein kinase inhibitor SB203580 (  B ). Magnification:  bar represents 20 μm. (  A ) Light micrograph of nerves treated with amitriptyline at 10 mm/approximately 0.3%. Application of 10 mm amitriptyline topically to rat sciatic nerve produces significant injury to nerve fibers in the subperineurial region of the nerve fascicle. Degenerated nerve fibers are particularly dominant (  arrow ) in the area adjacent to the presumed drug application. (  B ) Light micrograph of nerves treated with amitriptyline coadministered with SB203580. Sciatic nerves treated with 10 mm amitriptyline coadministered with 10 μm SB203580 were protected from the neurotoxic effects caused by amitriptyline. Note an essentially normal fascicle in which there is only minimal nerve fiber injury in the subperineurial space adjacent to the highest concentration of the anesthetic. The epineurial space is thickened and reactive, but the endoneurial space is only slightly hydropic.