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PAIN MEDICINE

A Single Intravenous Injection of KRN5500 (Antibiotic Spicamycin) Produces Long-Term Decreases in Multiple Sensory Hypersensitivities in Neuropathic Pain

L. A. Kobierski, MD PhD^*, S. Abdi, MD PhD, L. DiLorenzo, MD^*, N. Feroz, MD^*, and D. Borsook, MD PhD^*,

Departments of *Radiology, Anesthesia and Critical Care, and Neurology, Center for Functional Pain Neuroimaging and Therapy Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts

Address correspondence and reprint requests to David Borsook, MD, PhD, Center for Functional Pain Neuroimaging and Therapy Research, MGH NMR Center, Department of Radiology, Rm. 2316, Building 149, 13th St., Charlestown, MA 02129. Address e-mail to dborsook{at}partners.org

Neuropathic pain is a significant clinical problem. Currently, there are no drugs that produce complete amelioration of this type of pain. We have previously shown that KRN5500, a derivative of the antibiotic spicamycin, produces a prolonged (7-day), and significant reduction in neuropathic pain, but not nociceptive pain. Herein, we provide further evidence for the efficacy of this drug in inhibiting pain after IV injection in a spared nerve injury model of neuropathic pain. A single IV dose of the drug produces an increase in pain thresholds to punctuate mechanical stimuli and to cold stimuli over a period of 7 days, whereas IV injection of the vehicle is without any effect. No change in pain threshold was observed in the contralateral foot. In addition, a significant antiallodynic effect to mechanical stimuli was observed at 1, 2, 4, and 6 wk. The drug may be a potential candidate for cancer-related neuropathic pain as well as a marker for discovery of effective analgesics for neuropathic pain.

IMPLICATIONS: We examined the effect of a novel drug (KRN5500) on nerve damage pain. After the successful effects of this drug in a single human, we have shown that the drug infused as a single application at different doses in a rat model of nerve damage pain produces pain relief in this model for many weeks.