krn-5500 and Pain

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.. 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.

Topics: Animals; Cold Temperature; Hyperalgesia; Male; Neurons, Afferent; Pain; Pain Threshold; Peripheral Nervous System Diseases; Physical Stimulation; Purine Nucleosides; Rats; Rats, Sprague-Dawley; Weight Gain

We studied the effects of a spicamycin derivative, KRN5500, on two animal models of neuropathic pain (Chung and Bennett models) and a nociceptive pain model by using Complete Freund's adjuvant. After the establishment of mechanical allodynia by using the previously mentioned models, a single intraperitoneal injection of KRN5500 produced significant attenuation of mechanical allodynia in both neuropathic pain models. However, this effect was not observed in rats that had a nociceptive injury (Complete Freund's adjuvant). Furthermore, this experimental drug did not alter the mechanical pain threshold (by using von Frey filament test) on normal, uninjured rats. We have demonstrated that KRN5500 may have value in the treatment of neuropathic pain.

Topics: Analgesics; Analysis of Variance; Animals; Antibiotics, Antineoplastic; Disease Models, Animal; Freund's Adjuvant; Hindlimb; Injections, Intraperitoneal; Male; Nociceptors; Pain; Pain Threshold; Peripheral Nervous System Diseases; Placebos; Purine Nucleosides; Rats; Rats, Sprague-Dawley; Sciatic Neuropathy; Single-Blind Method; Spinal Nerves