Pathologic Processes of Lumbar Primary Sensory Neurons Produced by High Doses of Pyridoxine in Rats

―Morphometric and Electron Microscopic Studies―

Abstract

The morphologic effects of the toxicity of high doses of pyridoxine hydrochloride (vitamin B₆) on the lumbar primary sensory neurons in rats were studied. The test rats were treated with 1,200 mg/kg of pyridoxine hydrochloride by intraperitoneal injection once a day, and were sacrificed by perfusion at periods ranging from one to seven days after the injection, together with the control rats. Initial lesions consisted of eccentricity and crenation of the nucleus and vacuole formation in the cytoplasm of large dorsal root ganglion neurons, 2 days after the injection. These lesions were followed by segregation of the nucleolus, axon reaction-like changes in the cytoplasm and axonal degeneration of both peripheral axons in the sural nerve and central axons in the fasciculus gracilis. The frequency of teased myelinated fibers showing axonal degeneration during tests was significantly greater than in control 3 to 7 days after the injection. No significant difference of such frequency was found between the proximal and distal sural nerve during tests. The number of large myelinated fibers per nerve in the sural nerve, when compared with control, was preferentially decreased during tests. In the fasciculus gracilis, the decrease of the density of myelinated fibers was more pronounced in the third cervical segment than in the fifth thoracic segment. Because both peripheral and central axons were similarly affected and the initial lesions were found in the neuronal cell body, the mode of degeneration of axons in this study was regarded as "neuronopathy". By both light and electron microscopy, accumulation of mitochondria, vesicles, multilamellar and dense bodies were found in the nodal and distal paranodal axons of myelinated fibers in the sixth dorsal root ganglion on the 2nd day after the injection, which preceeded the degeneration of both peripheral and central axons. Such accumulation, revealed for the first time in this study, may reflect the presence of a blockade of the axoplasmic transport in the proximal axon and cell body of the lumbar primary sensory neuron and subsequently give rise to the degeneration of both peripheral and central axons of the lumbar primary sensory neuron. The pathologic alterations at the different sites of the lumbar primary sensory neuron revealed in this study should be taken into consideration for the better understanding not only of the pathogenesis of human pyridoxine-induced sensory neuropathy, but also of other human and experimental neuropathies.