The impact of morphine after a spinal cord injury
The impact of morphine after a spinal cord injury
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DOI：
10.1016/j.bbr.2007.02.035
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发表时间：
2007-05-16
影响因子：
2.7
通讯作者：
Grau, James W.
中科院分区：
文献类型：
--
作者：
Hook, Michelle A.;Liu, Grace T.;Grau, James W.
伤害性刺激的强度引起疼痛相关行为，减弱运动和膀胱功能的恢复，并增加挫伤后的组织损失。这些数据表明，伤害性输入（例如，来自组织损伤）可以增强损伤后的功能丧失，并且潜在的临床治疗，例如用镇痛药预处理，可以保护受损的系统免受进一步的继发性损伤。目前的研究检验了这一假设，并表明一种潜在的治疗方法（吗啡）没有保护作用。事实上，吗啡似乎加剧了伤害性刺激的效果。实验1表明，脊髓损伤后，需要20 mg/kg的全身吗啡来诱导强抗痛觉和阻断对休克治疗的行为反应，这一剂量远远高于假对照组所需的剂量。在实验2中，在不可控电刺激或单独约束前，给予挫伤大鼠三种剂量吗啡（Vehicle、10、20 mg/kg）中的一种。尽管吗啡降低了痛觉反应性，但它并没有减轻休克的长期后果。用吗啡和电击治疗的大鼠死亡率更高，三周后对无害的感觉刺激表现出异动反应。除了休克外，吗啡本身也破坏了感觉功能的恢复。用吗啡单独治疗的大鼠也明显比用生理盐水治疗的大。这些结果表明，尽管疼痛引发的行为受到抑制，但伤害性刺激仍会影响恢复。该结果具有重要的临床意义，因为它们表明阿片类药物治疗可能对损伤后的功能恢复产生不利影响。(c) 2007 Elsevier B.V.版权所有
Nociceptive stimulation, at an intensity that elicits pain-related behavior, attenuates recovery of locomotor and bladder functions, and increases tissue loss after a contusion injury. These data imply that nociceptive input (e.g., from tissue damage) can enhance the loss of function after injury, and that potential clinical treatments, such as pretreatment with an analgesic, may protect the damaged system from further secondary injury. The current study examined this hypothesis and showed that a potential treatment (morphine) did not have a protective effect. In fact, morphine appeared to exacerbate the effects of nociceptive stimulation. Experiment I showed that after spinal cord injury 20 mg/kg of systemic morphine was necessary to induce strong antinociception and block behavioral reactivity to shock treatment, a dose that was much higher than that needed for sham controls. In Experiment 2, contused rats were given one of three doses of morphine (Vehicle, 10, 20 mg/kg) prior to exposure to uncontrollable electrical stimulation or restraint alone. Despite decreasing nociceptive reactivity, morphine did not attenuate the long-term consequences of shock. Rats treated with morphine and shock had higher mortality rates, and displayed allodynic responses to innocuous sensory stimuli three weeks later. Independent of shock, morphine per se undermined recovery of sensory function. Rats treated with morphine alone also had significantly larger lesions than those treated with saline. These results suggest that nociceptive stimulation affects recovery despite a blockade of pain-elicited behavior. The results are clinically important because they suggest that opiate treatment may adversely affect the recovery of function after injury. (c) 2007 Elsevier B.V. All rights reserved.