PHARMACOLOGY OF HUMAN EXPERIMENTAL AND NEUROPATHIC PAIN

人类实验性疼痛和神经病理性疼痛的药理学

基本信息

  • 批准号:
    6187483
  • 负责人:
  • 金额:
    $ 10.56万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1998
  • 资助国家:
    美国
  • 起止时间:
    1998-07-01 至 2001-06-30
  • 项目状态:
    已结题

项目摘要

Animal models on pain emphasize that small afferent input leads to a facilitated state of hyperalgesia and allodynia. Parallel experimental models in humans have been developed using quantitative sensory testing (QST) and models using thermal pulses and subdermal capsaicin to evoke a state of hyperalgesia and allodynia. Preclinical studies have shown that these hyperpathic states in animals are mediated by a peripheral and spinal pharmacology distinct from that which mediates acute C fiber excitation. Several characteristics are noted: i) Acute high, but not low threshold afferent input is affected by mu, alpha 2 agonists, and NSAIDS; ii) A state is induced by small afferent input which is mediated in part by NMDA receptors; and iii) Injured nerves may induce a state mediated in part by spontaneous activity mediated by increased sodium channels. These observations suggest several hypotheses which reflect drug action in humans. 1) Mu, alpha 2 agonism, and NSAIDS will have little effect upon thermal and mechanical thresholds; will increase thermal and mechanical pain thresholds and, reduce secondary hyperalgesia induced by small afferent activation, whereas NMDA antagonism will have little effect upon acute thresholds, but will reduce the secondary hyperalgesia. 2) Sodium channel blockade will diminish the secondary hyperalgesia with minimum effect upon acute thresholds. Using QST for thermal and mechanical thresholds, the generation of a painful state with thermal pulses and intradermal capsaicin, and delivery of sodium channel blocker, mu opioid agonists, alpha-2-agonist, NSAIDS, NMDA antagonists, and some miscellaneous analgesic drugs by the oral and intravenous route, the hypotheses presented will be tested in humans. These experimental pain states are believed to reflect mechanisms underlying components of the post nerve injury pain state. Thus, based on hypotheses derived from our understanding of the pharmacology of afferent processing derived from preclinical work, this proposal seeks to define whether 1) certain receptor and channel mechanisms influence the experimental human pain models; and, 2) that certain clinical pain states are mediated by mechanisms which have a comparable pharmacology to experimental human pain models and the corresponding animal model. These studies will provide support for the premise that there is a correlation of mechanisms between experimental and clinical states and that the experimental models can predict clinical efficacy of agents in anomalous human pain states.
疼痛的动物模型强调,小传入输入导致一个 易化状态的痛觉过敏和异常性疼痛。 平行实验 已经使用定量感觉测试开发了人类模型 (QST)和模型使用热脉冲和皮下辣椒素, 痛觉过敏和异常性疼痛的状态。 临床前研究表明 动物的这些病态是由外周神经介导的, 和脊髓药理学不同,其介导急性C纤维 激发 注意到几个特点:i)急性高,但不是 低阈值传入输入受μ α 2激动剂的影响, NSAIDS; ii)状态由小传入输入诱导,其被介导 部分通过NMDA受体;和iii)受损的神经可以诱导一种状态, 部分由钠增加介导的自发活动介导 渠道这些观察提出了几个假设,反映了 药物在人体内的作用1)Mu,α 2激动剂和NSAIDS将具有 对热阈值和机械阈值几乎没有影响;将 增加热和机械疼痛阈值,并减少继发性 小传入激活引起的痛觉过敏,而NMDA 拮抗作用对急性阈值几乎没有影响,但 减轻继发性痛觉过敏。2)钠通道阻断将 减少继发性痛觉过敏,对急性 阈值。 使用QST的热和机械阈值, 用热脉冲和皮内产生疼痛状态 辣椒素和钠通道阻滞剂,μ阿片激动剂, α-2-激动剂、NSAIDS、NMDA拮抗剂和一些其他药物 口服和静脉注射镇痛药,假说 将在人类身上进行测试。 这些实验性疼痛状态是 据信反映了后神经成分的潜在机制 伤害疼痛状态。 因此,根据我们的假设, 了解传入处理的药理学, 在临床前工作中,该建议旨在确定1)某些 受体和通道机制影响实验性人类疼痛 模型;和,2)某些临床疼痛状态是由 具有与实验人类相当的药理学机制 疼痛模型及相应的动物模型。 这些研究将 为以下前提提供支持: 实验和临床状态之间的机制, 实验模型可以预测药物在异常 人类的痛苦状态

项目成果

期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Effect of chronic oral gabapentin on capsaicin-induced pain and hyperalgesia: a double-blind, placebo-controlled, crossover study.
长期口服加巴喷丁对辣椒素引起的疼痛和痛觉过敏的影响:一项双盲、安慰剂对照、交叉研究。
  • DOI:
    10.1097/ajp.0b013e3181673b93
  • 发表时间:
    2008
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Wallace,MarkS;Schulteis,Gery
  • 通讯作者:
    Schulteis,Gery
Postdelivery of alfentanil and ketamine has no effect on intradermal capsaicin-induced pain and hyperalgesia.
分娩后阿芬太尼和氯胺酮对皮内辣椒素引起的疼痛和痛觉过敏没有影响。
  • DOI:
    10.1097/00002508-200211000-00005
  • 发表时间:
    2002
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Wallace,MarkS;Braun,Jennifer;Schulteis,Gery
  • 通讯作者:
    Schulteis,Gery
Concentration-effect relationships for intravenous alfentanil and ketamine infusions in human volunteers: effects on acute thresholds and capsaicin-evoked hyperpathia.
人类志愿者静脉阿芬太尼和氯胺酮输注的浓度效应关系:对急性阈值和辣椒素诱发的过敏的影响。
  • DOI:
    10.1177/0091270002042001008
  • 发表时间:
    2002
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Wallace,MarkS;Ridgeway3rd,Beri;Leung,Albert;Schulteis,Gery;Yaksh,TonyL
  • 通讯作者:
    Yaksh,TonyL
The effect of chronic oral desipramine on capsaicin-induced allodynia and hyperalgesia: a double-blinded, placebo-controlled, crossover study.
长期口服地昔帕明对辣椒素引起的异常性疼痛和痛觉过敏的影响:一项双盲、安慰剂对照、交叉研究。
  • DOI:
    10.1097/00000539-200210000-00034
  • 发表时间:
    2002
  • 期刊:
  • 影响因子:
    5.7
  • 作者:
    Wallace,MarkS;Barger,Danielle;Schulteis,Gery
  • 通讯作者:
    Schulteis,Gery
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MARK S WALLACE其他文献

MARK S WALLACE的其他文献

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{{ truncateString('MARK S WALLACE', 18)}}的其他基金

California Clinical and Translational Pain Research Consortium
加州临床和转化疼痛研究联盟
  • 批准号:
    10888865
  • 财政年份:
    2019
  • 资助金额:
    $ 10.56万
  • 项目类别:
EFFICACY OF INHALED CANNABIS FOR THE TREATMENT OF PAINFUL DIABETIC NEUROPATHY
吸入大麻治疗疼痛性糖尿病神经病的功效
  • 批准号:
    8166826
  • 财政年份:
    2009
  • 资助金额:
    $ 10.56万
  • 项目类别:
EFFICACY OF INHALED CANNABIS FOR THE TREATMENT OF PAINFUL DIABETIC NEUROPATHY
吸入大麻治疗疼痛性糖尿病神经病的功效
  • 批准号:
    7950969
  • 财政年份:
    2008
  • 资助金额:
    $ 10.56万
  • 项目类别:
EFFECTS OF SPINAL CORD STIMULATION ON EXPERIMENTALLY INDUCED WIND-UP
脊髓刺激对实验诱导结束的影响
  • 批准号:
    7951020
  • 财政年份:
    2008
  • 资助金额:
    $ 10.56万
  • 项目类别:
ANALGESIC EFFICACY OF SMOKED CANNABIS IN REFRACTORY CANCER PAIN
熏制大麻对难治性癌痛的镇痛功效
  • 批准号:
    7205623
  • 财政年份:
    2003
  • 资助金额:
    $ 10.56万
  • 项目类别:
Analgesic Efficacy of Smoked Cannabis
熏制大麻的镇痛功效
  • 批准号:
    7045426
  • 财政年份:
    2003
  • 资助金额:
    $ 10.56万
  • 项目类别:
ANALGESIC EFFICACY OF SMOKED CANNABIS
熏制大麻的镇痛功效
  • 批准号:
    7205602
  • 财政年份:
    2003
  • 资助金额:
    $ 10.56万
  • 项目类别:
SNX-III ADMINISTERED TO PATIENTS WITH CHRONIC NON-MALIGNANT PAIN
SNX-III 用于慢性非恶性疼痛患者
  • 批准号:
    6117968
  • 财政年份:
    1998
  • 资助金额:
    $ 10.56万
  • 项目类别:
PHARMACOLOGY OF HUMAN EXPERIMENTAL AND NEUROPATHIC PAIN
人类实验性疼痛和神经病理性疼痛的药理学
  • 批准号:
    2891415
  • 财政年份:
    1998
  • 资助金额:
    $ 10.56万
  • 项目类别:
PHARMACOLOGY OF HUMAN EXPERIMENTAL AND NEUROPATHIC PAIN
人类实验性疼痛和神经病理性疼痛的药理学
  • 批准号:
    2692368
  • 财政年份:
    1998
  • 资助金额:
    $ 10.56万
  • 项目类别:

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