Abstract
Autotomy, self-mutilation of a denervated limb, is common in animals after peripheral nerve injury (PNI) and is a reliable proxy for neuropathic pain in humans. Understanding the occurrence and treatment of autotomy remains challenging. The objective of this study was to investigate the occurrence of autotomy in nude and Wistar rats and evaluate the differences in macrophage activation and fiber sensitization contributing to the understanding of autotomy behavior. Autotomy in nude and Wistar rats was observed and evaluated 6 and 12 weeks after sciatic nerve repair surgery. The numbers of macrophages and the types of neurons in the dorsal root ganglion (DRG) between the two groups were compared by immunofluorescence studies. Immunostaining of T cells in the DRG was also assessed. Nude rats engaged in autotomy with less frequency than Wistar rats. Autotomy symptoms were also relatively less severe in nude rats. Immunofluorescence studies revealed increased macrophage accumulation and activation in the DRG of Wistar rats. The percentage of NF200+ neurons was higher at 6 and 12 weeks in Wistar rats compared to nude rats, but the percentage of CGRP+ neurons did not differ between two groups. Additionally, macrophages were concentrated around NF200-labeled A fibers. At 6 and 12 weeks following PNI, CD4+ T cells were not found in the DRG of the two groups. The accumulation and activation of macrophages in the DRG may account for the increased frequency and severity of autotomy in Wistar rats. Our results also suggest that A fiber neurons in the DRG play an important role in autotomy.
Highlights
Peripheral nerve injury (PNI) is one of the most common clinical injuries and affects approximately 1 million people worldwide every year [1]
Autotomy was observed in Wistar rats within one week, as early as 4 days
We found no significant difference in the percentage of NF200+ neurons in the dorsal root ganglion (DRG) between nude and Wistar rats (39.60% ± 2.11 vs. 39.16% ± 1.77, p > 0.05) in sham rats
Summary
Peripheral nerve injury (PNI) is one of the most common clinical injuries and affects approximately 1 million people worldwide every year [1]. Self-mutilation of a denervated limb [5,6,7,8], is very common in animals after PNI (e.g., mice, rats, and rabbits), especially in rats after sciatic nerve transection, when the incidence of autotomy reaches as high as 40–80% [5,7,9]. This behavior is painful and affects animal behavioral outcomes. There is a limited understanding of the mechanisms that cause autotomy
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