Inhibitory effect of lidocaine on pain and itch using formalin-induced nociception and 5'-guanidinonaltrindole-induced scratching models in mice: behavioral and neuroanatomical evidence.

Inhibitory effect of lidocaine on pain and itch using formalin-induced nociception and 5'-guanidinonaltrindole-induced scratching models in mice: behavioral and neuroanatomical evidence.
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DOI:
10.1016/j.ejphar.2009.06.026
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发表时间:
2009-08-15
影响因子:
5
通讯作者:
Cowan A
Cowan A
中科院分区:
医学2区
文献类型:
--
作者:
Inan S;Dun NJ;Cowan A

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本研究的目的是建立利多卡因,局部麻醉剂,对疼痛和瘙痒的影响,使用福尔马林诱导的伤害性和κ阿片拮抗剂诱导的抓挠小鼠模型。我们研究了用利多卡因N-乙基溴(利多卡因,2%,0.1 ml)局部皮内预处理(-10 min)是否拮抗疼痛和瘙痒诱导的行为反应并阻止c-fos表达。使用雄性Swiss韦伯斯特小鼠(25-30 g,n=6-10)。福尔马林(5%,20 µl,s.c.)或盐水给药于右背后爪,并在0-10分钟和20-35分钟记录舔该爪所花费的时间。对于瘙痒,用5′-胍基那曲吲哚(GNTI,0.3 mg/kg,s.c.,颈后)或生理盐水,并计数用后爪进行的颈向抓挠的数目,持续30分钟。在相应处理后2小时,在腰椎(用于疼痛)和颈椎(用于抓挠)脊髓切片中进行C-fos免疫组织化学。我们发现利多卡因(a)拮抗福尔马林诱导的疼痛和GNTI诱导的抓挠,(B)阻止疼痛(背角浅层内侧和深层)和瘙痒(背角浅层外侧)诱发的c-fos表达。此外,GNTI在戴着铁环(以防止抓挠颈部)的小鼠中引起c-fos激活,表明GNTI通过诱导瘙痒感来激发c-fos表达。我们的研究结果突出了利多卡因的抗过敏特性,并认为其对过敏状态的全面临床试验。
The aim of this study was to establish the effect of lidocaine, a local anesthetic, on pain and itch using formalin-induced nociception and kappa opioid antagonist-induced scratching models in mice. We investigated if local intradermal pretreatment (at −10 min) with lidocaine N-ethyl bromide (lidocaine, 2%, 0.1 ml) antagonizes behavioral responses and prevents c-fos expression induced by pain and itch. Male, Swiss Webster mice (25–30 g, n=6–10) were used. Formalin (5%, 20 µl, s.c.) or saline was administered to the right dorsal hindpaw and the time spent licking this paw was recorded at 0–10 min and 20–35 min. For itching, mice were challenged with 5′- guanidinonaltrindole (GNTI, 0.3 mg/kg, s.c., behind the neck) or saline and the number of neck-directed scratches with hindpaws was counted for 30 min. C-fos immunohistochemistry was performed in lumbar (for pain) and cervical (for scratching) spinal sections 2 h after respective treatments. We found that lidocaine (a) antagonizes both formalin-induced pain and GNTI-induced scratching and (b) prevents c-fos expression evoked by pain (medial side of the superficial layer and deeper layers of the dorsal horn) and itch (lateral side of the superficial layer of the dorsal horn). Additionally, GNTI caused c-fos activation in mice wearing an Elizabethan collar (to prevent scratching of the neck) suggesting that GNTI provokes c-fos expression by inducing an itch sensation. Our results highlight the antipruritic properties of lidocaine and argue for its comprehensive clinical testing against pruritic states.
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