Spinal NK-1 receptor-expressing neurons and descending pathways support fentanyl-induced pain hypersensitivity in a rat model of postoperative pain
Spinal NK-1 receptor-expressing neurons and descending pathways support fentanyl-induced pain hypersensitivity in a rat model of postoperative pain
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DOI：
10.1111/j.1460-9568.2009.06616.x
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发表时间：
2009-02-01
影响因子：
3.4
通讯作者：
Malan, T. P.
中科院分区：
文献类型：
--
作者：
Rivat, Cyril;Vera-Portocarrero, Louis P.;Malan, T. P.
临床上重要的阿片类芬太尼，在足底切开引起的手术疼痛模型中，急性给药可增强机械过敏。神经激肽-1(NK-1)受体表达的上行脊髓神经元的活性、起源于延髓头端腹内侧(RVM)的下行通路和脊髓强啡肽是持续吗啡暴露期间痛敏发生和维持所必需的，提示这些机制在阿片类药物增强手术疼痛中也可能是重要的。因此，我们研究了这些机制在非手术切开和足底切开大鼠急性芬太尼注射所产生的感觉超敏反应中的作用。在非手术大鼠中，如前所述，芬太尼诱导的止痛之后是即刻和持久的感觉过敏。芬太尼还能增强足底切开引起的疼痛敏感性。用P-Saporin物质预处理来消融表达NK-1的脊髓神经元可以降低芬太尼治疗的大鼠的感觉超敏反应，在较小程度上减少手术切开的芬太尼治疗的大鼠的感觉过敏反应。RVM内微量注射利多卡因可完全逆转芬太尼诱导的感觉超敏反应和芬太尼对切口诱导的感觉超敏反应的增强作用。在无芬太尼预处理的情况下，利多卡因静脉注射可轻微减轻切开引起的感觉过敏反应。芬太尼和芬太尼/切口组大鼠脊髓强啡肽含量分别增加30+/-7%和66+/-17%。脊髓注射强啡肽抗血清可减轻芬太尼治疗大鼠的感觉超敏反应。这些数据支持含有NK-1受体的上行通路的部分作用和下行易化通路在芬太尼诱导的痛敏和手术切开后芬太尼治疗所产生的痛敏增强中的关键作用。
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.