Amiodarone decreases heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain.
Lidocaine is effective in controlling ventricular dysrhythmia and neuropathic pain. Amiodarone, like lidocaine, has sodium channel blocking properties. In the present study we explore whether amiodarone has a similar effect as lidocaine on the heat, cold, and mechanical hyperalgesia seen in the rat model of neuropathic pain. Ten male Sprague-Dawley rats were anesthetized. Four loose ligatures were placed on the sciatic nerve of the right hindpaw. A sham operation was performed on the contralateral hindpaw (control). Heat hyperalgesia was determined by comparing each paw withdrawal latency to heat stimulation (radiant heat source, 50 degrees C). Cold hyperalgesia was assessed with acetone application. Mechanical hyperalgesia was determined by comparing the mechanical threshold in the ligated and control hind paws using calibrated von Frey filaments. Amiodarone was intraperitoneally administered at doses of 1, 5, 10, 20, 50, and 100 mg/kg after the development of hyperalgesia. The animals were tested for hyperalgesia before and 1, 3, and 24 h after the administration of a single dose of amiodarone. Intrathecal catheters were implanted in 5 new rats, and amiodarone 5 mg/kg was injected. Testing for heat, mechanical, and cold hyperalgesia was performed similarly in the intrathecal amiodarone administration group. Amiodarone produces statistically significant decreases of heat, cold, and mechanical hyperalgesia after intraperitoneal administration. Results are statistically significant at 10 mg/kg (heat hyperalgesia), 20 mg/kg (mechanical hyperalgesia), and 100 mg/kg (cold hyperalgesia) intraperitoneally. Hyperalgesia returns 24 h after a dose. The intrathecal administration of amiodarone produces a nonstatistically significant reduction of hyperalgesia. Amiodarone seems to have a similar effect as lidocaine on the hyperalgesia seen in the rat model of neuropathic pain. As the half-life of amiodarone is significantly longer that that of lidocaine (mean, 53 days versus 90 min) in humans, it may have the potential to provide a longer lasting (and perhaps more effective) effect than lidocaine on neuropathic pain states.


CONCLUSIONS
Amiodarone was found to produce a statistically significant decrease in heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain after intraperitoneal injection. Considering its long half-life in humans, amiodarone has the potential to provide long lasting pain relief in neuropathic pain states.
Datta
Sukdeb
S
From the Department of Anesthesiology and Pain Management, Cook County Hospital, Chicago, Illinois.
Waghray
Taruna
T
Torres
Maria
M
Glusman
Silvio
S
D000638:Amiodarone / Q000627:therapeutic use*; D000779:Anesthetics, Local / Q000627:therapeutic use; D000818:Animals; D003080:Cold Temperature; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007274:Injections, Intraperitoneal; D008012:Lidocaine / Q000627:therapeutic use; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000150:complications; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000779:Anesthetics, Local; D014665:Vasodilator Agents; D008012:Lidocaine; D000638:Amiodarone