The clinically important
opioid fentanyl, administered acutely, enhances mechanical
hypersensitivity in a model of surgical
pain induced by plantar incision. Activity of neurokinin-1 (NK-1) receptor-expressing ascending spinal neurons, descending pathways originating in the rostral ventromedial medulla (RVM), and spinal
dynorphin are necessary for the development and maintenance of
hyperalgesia during sustained
morphine exposure, suggesting that these mechanisms may also be important in
opioid enhancement of surgical
pain. Therefore, we examined the roles of these mechanisms in sensory
hypersensitivity produced by acute
fentanyl administration in rats not undergoing
surgical incision and in rats undergoing plantar incision. In non-operated rats,
fentanyl induced
analgesia followed by immediate and long-lasting sensory
hypersensitivity, as previously described.
Fentanyl also enhanced
pain sensitivity induced by plantar incision. Ablation of NK-1-expressing spinal neurons by pre-treatment with
substance P-Saporin reduced sensory
hypersensitivity in
fentanyl-treated rats and, to a lesser extent, in
fentanyl-treated rats with a
surgical incision. Microinjection of
lidocaine into the RVM completely reversed
fentanyl-induced sensory
hypersensitivity and
fentanyl enhancement of incision-induced sensory
hypersensitivity. RVM
lidocaine injection resulted in a slight reduction of incision-induced sensory
hypersensitivity in the absence of
fentanyl pre-treatment. Spinal
dynorphin content increased by 30 +/- 7% and 66 +/- 17% in
fentanyl- and
fentanyl/incision-treated rats. Spinal administration of antiserum to
dynorphin attenuated sensory
hypersensitivity in
fentanyl-treated rats. These data support a partial role of
NK-1 receptor-containing ascending pathways and a crucial role of descending facilitatory pathways in
fentanyl-induced
hyperalgesia and in the enhanced
hyperalgesia produced by
fentanyl treatment following
surgical incision.