Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7224-9. doi: 10.1073/pnas.1017719108. Epub 2011 Apr 11.
Dramatically up-regulated in the dorsal horn of the mammalian spinal cord following inflammation or nerve injury, neuropeptide Y (NPY) is poised to regulate the transmission of sensory signals. We found that doxycycline-induced conditional in vivo (Npy(tet/tet)) knockdown of NPY produced rapid, reversible, and repeatable increases in the intensity and duration of tactile and thermal hypersensitivity. Remarkably, when allowed to resolve for several weeks, behavioral hypersensitivity could be dramatically reinstated with NPY knockdown or intrathecal administration of Y1 or Y2 receptor antagonists. In addition, Y2 antagonism increased dorsal horn expression of Fos and phosphorylated form of extracellular signal-related kinase. Taken together, these data establish spinal NPY receptor systems as an endogenous braking mechanism that exerts a tonic, long-lasting, broad-spectrum inhibitory control of spinal nociceptive transmission, thus impeding the transition from acute to chronic pain. NPY and its receptors appear to be part of a mechanism whereby mammals naturally recover from the hyperalgesia associated with inflammation or nerve injury.
在哺乳动物脊髓背角中，神经肽 Y（NPY）在炎症或神经损伤后显著上调，准备调节感觉信号的传递。我们发现，强力霉素诱导的体内条件性（Npy(tet/tet)）NPY 敲低导致触觉和热敏感性的强度和持续时间迅速、可逆和可重复增加。值得注意的是，当允许解决数周时，行为过敏可以通过 NPY 敲低或鞘内给予 Y1 或 Y2 受体拮抗剂显著重新出现。此外，Y2 拮抗作用增加了背角中 Fos 和细胞外信号相关激酶磷酸化形式的表达。总之，这些数据确立了脊髓 NPY 受体系统作为一种内源性制动机制，对脊髓伤害性传递产生持续、广泛的抑制控制，从而阻碍了从急性到慢性疼痛的转变。NPY 及其受体似乎是哺乳动物从与炎症或神经损伤相关的痛觉过敏中自然恢复的机制的一部分。
