Utility of Decompressive Surgery in the Prophylaxis and Treatment of Cisplatin Neuropathy in Adult Rats

Abstract

Cisplatin produces a dose-dependent and dose-limiting peripheral neuropathy in patients. This study tested the hypothesis that this clinical neuropathy results from the chronic compression of peripheral nerves rendered susceptible to injury because of cisplatin-induced microtubular dysfunction. A quantitative model of cisplatin neurotoxicity was developed by administering cisplatin to rats and measuring the neuropathy by hindlimb walking track assay. The study aims were: (1) to characterize neuropathy induced by cisplatin in the adult rat; (2) to evaluate the role of decompressive surgery in the prevention of cisplatin neuropathy; and (3) to determine whether decompressive surgery was an effective treatment for established neuropathy. The assay demonstrated an increased print length in animals after 8 weeks of cisplatin (p < 0.01). This neuropathy progressed for 6 weeks after cisplatin was stopped, and reversed slowly over 3 months. These abnormalities were prevented by early tarsal tunnel decompression. Decompressive surgery was also beneficial, if performed early in the course of the neuropathy; abnormalities reversed in 5 weeks and remained normal for the remainder of the study. Control animals had progressive abnormalities which slowly resolved over a period of 18 weeks after discontinuing cisplatin. However, decompressive surgery performed after the neuropathy was established did not alter the neuropathic walking-track pattern. These studies provide insight into the etiology and possible therapeutic approaches to cisplatin neuropathy. Although further studies are required, they suggest that, in selected patients, decompressive surgery may have a role in the prevention or early treatment of cisplatin-induced neuropathy. Patients with underlying clinical or subclinical compressive neuropathies could be at high risk for the development of cisplatin neuropathy, and quantitative monitoring of neuropathies may be useful.

Diabetic Neuropathy: Review of a Surgical Approach to Restore Sensation, Relieve Pain, and Prevent Ulceration and Amputation

“…This research model also has been applied to the neuropathy related to the chemotherapeutic drug cisplatin. 40 That study extended the observations made in the diabetic rat model in that decompression of the tarsal tunnel in rats with cisplatin neuropathy restored normal walking track patterns. These results were independently confirmed by a group of investigators 23 using the identical model who reported that peripheral nerve function improved in diabetic rats when there was no tarsal tunnel compression present and additional functional improvement, as determined by walking track, analysis, resulted from opening the epineurium.…”

Animal Models of Cancer Pain

“…135 Although cisplatin-induced neuropathy progressed for 6 wk after discontinuation of the drug and slowly reversed over 3 mo, this side effect could be prevented by early decompressive surgery. 161 Models of pain from spontaneous cancer A natural model of cancer pain involves using animals that have spontaneously occurring tumors. Such models have been used recently to evaluate improved therapeutic approaches to treating cancer pain.…”

Surgical treatment of superimposed nerve compressions in hepatitis C neuropathy

“…33,34 A rat model of cisplatin-induced neuropathy revealed that early nerve decompression surgery would prevent walking track abnormalities. 35 Six patients with chemotherapyinduced neuropathy treated by multiple nerve decompressions were documented to have improved sensation along with a significant decrease in their pain. 6 Several papers have also been published showing specifically that carpal tunnel decompression in patients with diabetic neuropathy will give a significant improvement to those patients.…”