Presented at the 2013 AAPM Annual Meeting « Back

Ultra-Low Dose Fentanyl Prevents the Development of Neuropathic Pain in Rats

Paul Sloan, MD, paulsloan1956@yahoo.com¹, Elzbieta P. Wala, PhD¹, (1) University of Kentucky College of Medicine, Department of Anesthesiology, Lexington, Kentucky

Introduction: Chronic administration of opioids may cause opioid-induced hyperalgesia (OIH). In previous experiments, repeated administration of ultra-low dose (ULD) morphine resulted in development of tolerance to OIH. The aim of this study was to determine, in a rat model of neuropathic pain (chronic constriction nerve injury, CCI), if an ULD of fentanyl would inhibit the development of post-nerve-injury neuropathic pain. Methods: Fentanyl 0.5-500 ng/kg IP was administered acutely in non-injured rats. Chronic fentanyl (5ng/kg/day IP) therapy was initiated either immediately after CCI surgery or when neuropathy was established in nerve-injured rats. Saline served as control. Analgesic responsiveness was assessed using tail-flick and paw-pressure tests, respectively, in intact and CCI rats. Results: An ULD of fentanyl evoked pain sensitization in non-injured rats. This effect was related to dose (inversely), gender (female>male), and was reversed by ketamine. Neuropathy developed after CCI in control rats. This was not observed in rats of either sex exposed to ULD of fentanyl on day 1-28 post-CCI. Rats treated with ULD of fentanyl from day 7 after CCI exhibited hyperalgesia similar to control rats. Conclusions: 1) Pre-emptive use of an ULD of fentanyl blocked initiation (not maintenance) of neuropathic pain after peripheral nerve injury (CCI) in rats. 2) Established hyperalgesia (d7-14 after CCI) was not reversed by ULD fentanyl, suggesting that a source of this inhibitory process is prior to descending facilitation. 3) ULD of fentanyl given preoperatively and continued perioperatively may prevent the development of chronic postsurgical pain. References: 1) Angst MS. Anesthesiology 2006; 104:570-587 2) Wala EP. J Opioid Management 2011; 7:377-389 3) Katz J. Expert Rev Neurother 2009; 9:723-744.

Funding: None

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