Rivat C, Vera-Portocarrero LP, Ibrahim MM, Mata HP, Stagg NJ, De Felice M, Porreca F, Malan TP (2006) Ascending and descending pathways support fentanyl-induced pain hypersensitivity with and without a surgical incision. Neuroscience 2006 Abstracts 248.10. Society for Neuroscience, Atlanta, GA.
Summary: Acutely administered the analgesic opioid fentanyl has been shown to enhance mechanical hypersensitivity in a model of surgical pain induced by hindpaw incision in the rat. Recent evidence showed the importance of descending pathways originating from the rostral ventromedial medulla (RVM) in opioid-induced hyperalgesia after sustained morphine administration. Such hyperalgesia is also associated with numerous neurochemical changes in primary afferent fibers and spinal dorsal horn, such as increased spinal dynorphin expression. These changes may activate ascending pathways, mediated in part by NK-1 neurotransmission. Here, we examined the roles of ascending and descending pathways in sensory hypersensitivity after acute fentanyl administration. Male Sprague-Dawley rats received 4 fentanyl (4×100 μg/kg, s.c.) or saline injections administered at 15 min intervals. Some animals also received an incision in the plantar hindpaw. Thermal hyperalgesia and tactile allodynia were measured daily. In control rats, fentanyl induced analgesia followed by an immediate and long-lasting hyperalgesia, as previously described. Fentanyl also enhanced pain sensitivity induced by plantar incision. In SP-saporin pretreated rats, fentanyl induced analgesia and a moderate long-lasting hyperalgesia. The SP-saporin pretreatment slightly reduced both hyperalgesia and allodynia in postoperative rats and, to a larger extent, in fentanyl treated rats. Lidocaine injection in the RVM completely reversed fentanyl-induced sensory hypersensitivity and fentanyl enhancement of incision-induced hyperalgesia and allodynia. A slight reduction of incision-induced sensory hypersensitivity was observed after lidocaine injection in rats without fentanyl pretreatment. Spinal dynorphin content increased by 30 ± 7% and 71 ± 33% in fentanyl and fentanyl/incision treated rats, respectively. These data support the crucial role of the descending pathways from the RVM in the fentanyl-induced hyperalgesia and the partial implication of the NK-1 receptor containing ascending pathways.
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