Changes in features of degenerating primary sensory neurons with time after capsaicin treatment

Abstract

Capsaicin (50 mg/kg) was injected into new born mice and 5 and 12 h, and 1, 2, 3, and 5 days later, their lumbar dorsal root ganglia (DRG) with the nerve roots were fixed by immersion. The morphological changes which ensued with time after treatment were examined by light and electron microscopy. The findings were as follows: (a) rapid degeneration of certain smaller B-type neurons, indicating their prompt death, was seen 5 h after treatment. Later, accumulated neurofilaments appeared in larger B-type neurons. Fissures of the cytoplasm and cell fragmentation were also observed as particular features of degeneration. Finally, these degenerating neurons, destined to die, appeared as small round figures with a disorganized nucleus. Severely degenerated neurons were seen throughout the survival time after treatment, but seemed to be most numerous after 2-3 days. (b) Three days after treatment the Nissl substances of large A-type neurons appeared dispersed, forming ring-like bundles in the periphery of cells. Cytoplasmic rupture and large membrane-bound spaces with fine granular or fibrillar materials, indicating peripheral cytolysis, were also conspicuous. Some of these cells showed severe degeneration clearly leading to cell death. The A-type neurons began to degenerate later than the B-type neurons. (c) Satellite cells showed an increased amount of electron-opaque cytoplasm that contained large vacuoles and neuronal cell debris. Mitotic figures were increased in satellite cells 3 days after treatment. (d) Unmyelinated axons in the dorsal root of mice treated with capsaicin became enlarged with accumulation of neurofilaments, synaptic vesicles or various kinds of vesicles, multivesicular bodies and mitochondria. Numerous dense lamellar bodies appeared in the unmyelinted axons within DRG 3 days after treatment, but were scarcely seen in the dorsal roots. Degeneration of the myelinated fibers increased with time. Interestingly, capsaicin seemed to have both a direct and indirect action on DRG neurons: its direct action induced rapid degeneration of the smaller neurons, whereas its indirect action induced relatively slow degeneration of the larger neurons, causing chromatolytic changes similar to those induced by periphal nerve axotomy. The injury to DRG neurons due to the indirect action seemed to be induced retrogradely.