Clinical and electrophysiological expression of deafferentation pain alleviated by dorsal root entry zone lesions in rats

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Object. The aims of this study were to construct an animal model of deafferentation of the spinal cord by brachial plexus avulsion and to analyze the effects of subsequent dorsal root entry zone (DREZ) lesions in this model. To this end, the authors measured the clinical and electrophysiological effects of total deafferentation of the cervical dorsal horn in rats and evaluated the clinical efficacy of cervical DREZ lesioning.

Methods. Forty-three Sprague—Dawley rats were subjected to total deafferentation of the right cervical dorsal horn by performing a posterior rhizotomy from C-5 to T-1. The clinical effects of this deafferentation, namely self-directed mutilations consisting of scraping and/or ulceration of the forelimb skin or even autotomy of some forelimb digits, were then evaluated. As soon as some of these clinical signs of pain appeared, the authors performed a microsurgical DREZ rhizotomy ([MDR], microincision along the deafferented DREZ and dorsal horn). Before and after MDR, single-unit recordings were obtained in the deafferented dorsal horn and in the contralateral (healthy) side. The mean frequency of spontaneous discharge from the deafferented dorsal horn neurons was significantly higher than that from the healthy side (36.4 Hz compared with 17.9 Hz, p = 0.03).

After deafferentation, 81.4% of the rats developed clinical signs corresponding to pain following posterior rhizotomy. Among these animals, scraping was observed in 85.7% of cases, ulceration (associated with edema) in 37.1%, and autotomy in 8.5%. These signs appeared a mean 5.7 weeks (range 1–12 weeks) after deafferentation.

Thirteen rats benefited from an MDR; nine (69%) experienced a complete cure, that is, a total resolution of scraping or ulceration (a mean 4.6 weeks after MDR). In contrast, only one of 11 sham-operated animals showed signs of spontaneous recovery (p = 0.01).

Conclusions. These results emphasize the role of the spinal dorsal horn in the genesis of deafferentation pain and suggest that dorsal horn deafferentation by cervical posterior rhizotomy in the rat provides a reliable model of chronic pain due to brachial plexus avulsion and its suppression by MDR.

Article Information

Address reprint requests to: Marc Guenot, M.D., Department of Functional Neurosurgery, P. Wertheimer Hospital, 59, Boulevard Pinel, 69003 Lyon, France. email: marc.guenot@chu-lyon.fr.

© AANS, except where prohibited by US copyright law.

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Figures

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    Left: Photograph illustrating an example of a scraping lesion (arrows) along the right forearm. Right: Photograph depicting an example of an ulcerative lesion (arrow) of the digit, associated with edema of the entire forelimb paw.

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    Upper: Pie chart indicating the types of clinical signs of self-inflicted mutilations (before MDR). Lower: Pie chart demonstrating the topographic distribution of the scraping phenomena (before MDR). N = number of rats; ulc. = ulceration.

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    Graph demonstrating the time course of the appearance of the first clinical sign of self-directed mutilation.

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    Electrophysiological recordings of spontaneous single-unit activity of deafferented dorsal horn neurons (right C-7, upper), compared with nondeafferented ones (left C-7, lower). The deafferented dorsal horn neurons tend to display a significantly higher spontaneous firing rate than the nondeafferented ones.

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    Photographs illustrating evidence of complete cure. Left: Before MDR, there was scraping of the forearm (arrows). Right: Five weeks after MDR, the forearm skin recovered and regained a normal aspect, indicating a complete cure.

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    Graph depicting the time course of complete cure after MDR.

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    Photomicrograph exhibiting a histological section of the spinal cord (50-µm horizontal slice) post-MDR displaying a selective lesion involving the right dorsal horn and DREZ (arrow).

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