Previous work has demonstrated that
neuropeptide tyrosine (NPY), Y(1) receptor and Y(2) receptor are critical in modulation of
pain after nerve injury. We hypothesized that NPY was important for nociception after
surgical incision. As a model of
postoperative pain, rats underwent a plantar incision in one hindpaw. Western blots were used to quantify changes in
protein expression of NPY, Y(1) receptor and Y(2) receptor after incision in skin, muscle, and dorsal root ganglion (DRG).
Pain-related behaviors were tested after incision in rats treated with intrathecal NPY, Y(1) receptor antagonist (
BIBO3304--Chemical Name: N-[(1R)-1-[[[[4-[[(Aminocarbonyl)amino]methyl]phenyl]methyl]amino]carbonyl]-4-[(aminoiminomethyl)amino]butyl]-α-phenyl-benzeneacetamide ditrifluoroacetate), Y(2) receptor antagonist (
BIIE0246--Chemical Name: N-[(1S)-4-[(Aminoiminomethyl)amino]-1-[[[2-(3,5-dioxo-1,2-
diphenyl-1,2,4-triazolidin-4-yl)ethyl]amino]carbonyl]butyl]-1-[2-[4-(6,11-dihydro-6-oxo-5H-dibenz[b,e]azepin-11-yl)-1-piperazinyl]-2-oxoethyl]-cyclopentaneacetamide), combined NPY+antagonists,
morphine, or vehicle.
Pain behaviors were tested after incision in rats treated with locally applied intraplantar
injections of NPY, Y(1) receptor and Y(2) receptor antagonists or vehicle. NPY
protein expression was significantly downregulated in muscle for two days after incision. In contrast, Y(1) receptor and Y(2) receptor
protein expression was upregulated in both skin and muscle. A single
intrathecal injection of NPY reduced cumulative guarding
pain scores, as did
morphine. The intrathecal administration of Y(2) receptor antagonist also reduced
pain scores; findings that were not observed when drugs were administered locally. Intrathecal Y(2) receptor antagonists and NPY improved mechanical threshold and heat withdrawal latency 2h after incision. Intrathecal administration of NPY and/or central blockade of Y(2) receptor attenuated
pain behaviors early after incision (postoperative day (POD) 1-2). Y(1) receptor antagonist administration blocked the anti-hyperalgesic effect of NPY. Together these data suggest a role for spinal NPY in
postoperative pain.