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Acta Diabetol. 2010 Nov
23. [Epub ahead of print]
Systemic and spinal administration of etanercept,
a tumor necrosis factor alpha inhibitor, blocks tactile allodynia
in diabetic mice.
Dogrul
A, Gul H, Yesilyurt
O, Ulas UH, Yildiz
O.
Department of Pharmacology, Gulhane
Military Academy of Medicine, 06018, Etlik, Ankara, Turkey,
dogrula@gata.edu.tr.
Abstract
Painful diabetic neuropathy is one of the most
common forms of neuropathic pain syndromes. Tumor necrosis factor
alpha (TNF-alpha) is a proinflammatory cytokine that has been
implicated as a key pain mediator in the development and
maintenance of neuropathic pain conditions. Recent studies showed
that endogenous TNF-alpha production was also accelerated in neural
tissues and spinal cord under chronic hyperglycemia. Thus, in this
study, we investigated whether pharmacological inhibition of
TNF-alpha by etanercept, a TNF-alpha antagonist, could block
behavioral sign of diabetic neuropathic pain. Diabetes was induced
by streptozotocin (STZ) (200 mg/kg, i.p.) in
Balb-c mice and behavioral tests were performed between 45 and
60 days after STZ administration. Mechanical and
thermal sensitivities were measured by a series of calibrated Von
Frey filaments and hot plate test, respectively. Etanercept was
given by either intravenous (i.v.), intrathecal (i.th.) or
intraplantar (i.pl.) routes to the diabetic mice. Tactile
allodynia, but not thermal hyperalgesia, developed in diabetic
mice. Both i.v. (1, 10 and 20 mg/kg) or i.th. (1,
5 and 10 μg/mouse) treatments with etanercept
produced dose dependent reversal of tactile allodynia in diabetic
mice. However, etanercept was found to be inactive against
allodynia when given i.pl. (1, 5 and 10 μg/mouse).
Our results suggest that etanercept has promising effects on
diabetic neuropathic pain with antiallodynic effects when given
systemically or intrathecally.
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全身和鞘内注射依那西普抑制糖尿病小鼠的触觉异常痛敏
Dogrul A, et al.Acta Diabetol. 2010 Nov 23.
疼痛性糖尿病神经病变是一种常见的神经源性疼痛综合征。TNFα是一种促炎症因子，是产生和维持神经源性疼痛的重要介质。最近研究显示在慢性高血糖症中，神经组织和脊髓的内源性TNFα生成加速。本研究旨在探讨依那西普抑制TNFα能否阻止糖尿病神经源性疼痛的行为表现。腹腔注射链脲霉素（200 mg/kg）诱导Balb-c小鼠糖尿病，注射后45至60天进行行为检测。采用Von
Frey丝和热板法分别检测机械敏感度和热敏度。给予糖尿病小鼠静脉、鞘内或足底注射依那西普。糖尿病小鼠出现触觉异常痛敏，而非热痛觉过敏。静脉（1, 10,
20 mg/kg）和鞘内（1, 5,
10 μg/鼠）注射依那西普导致剂量依赖性触觉异常痛敏逆转，足底注射（1, 5,
10 μg/鼠）无效。结果提示全身或鞘内注射依那西普可能在糖尿病神经源性疼痛中有抗异常痛敏的作用。
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