(351) The Opioids Oxycodone, Fentanyl, and Morphine Amplify Neuropathic when Given after Chronic Pain is Established

Abstract

Neuropathic pain affects approximately 4 million people in the U.S. and remains refractory to analgesics in many patients. We have previously shown that a short course of morphine given at the time of initial chronic pain development results in amplification of the intensity and/or duration of neuropathic pain. However, it is unknown whether this effect is exclusive to morphine, or whether this effect is dependent on the time of dosing relative to the time of nerve injury. To test whether other common, clinically used opioids also exacerbate neuropathic pain, we tested the effects of fentanyl and oxycodone compared to morphine in a rat model of neuropathic pain, chronic constriction injury (CCI). Male Sprague Dawley rats received CCI surgery and were dosed with oxycodone (s.c. 2 mg/kg, b.i.d.), fentanyl (0.01mg/kg/hr s.c. osmotic minipump), morphine (s.c. 5 mg/kg, b.i.d.), or vehicle beginning 1 hour, 10 days, or 28 days post-CCI for 5 days. Previous experiments have shown that pain amplification occurs when morphine administration begins at day 10 after CCI (at the time of chronic pain development). We found that dosing with morphine, oxycodone, or fentanyl that begins at either day 10 or day 28 after injury results in prolonged magnitude and duration of chronic pain. This effect is not observed when the 5-day administration of these opioids began one-hour post CCI, before chronic pain onset. This suggests that opioids administered after the development of chronic pain can produce detrimental and counterproductive increases in pain, whereas a short course of opioids administered at the time of injury may not produce such effects. Whether patients with ongoing neuropathic pain (relative to those with acute nerve injury) are particularly sensitive to the deleterious effects of opioids warrants investigation. Supported by Dept of the Army Log No. 14001001. Opioids provided by the NIDA Drug Repository.