Stemming the opioid-induced pain cascade via cannabinoid modulation

通过大麻素调节阻止阿片类药物引起的疼痛级联反应

基本信息

  • 批准号:
    10218325
  • 负责人:
  • 金额:
    $ 20.13万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-07-01 至 2023-06-30
  • 项目状态:
    已结题

项目摘要

Despite their abuse potential, opioids remain a gold standard analgesic. One of the lesser discussed effects of chronic opioid use is opioid induced hyperalgesia (OIH), or increased pain sensitivity in some users. OIH persists for a longer duration than opioid withdrawal and may contribute to drug seeking and relapse in people with substance use disorders. The physiological causes of OIH are caused by (1) repeated µ opioid activation and desensitization, and (2) activation of inflammatory pathways by morphine binding to Toll-like receptor 4. Cannabinoids have well established analgesic and anti-inflammatory properties. Endogenous cannabinoids (i.e., endocannabinoids) have anti-inflammatory effects with limited intoxicating effects, as compared with exogenous cannabinoids. The proposed study will use an experimental animal model of repeated morphine exposure, followed by paw incision injury. Our goal is to test the hypothesis that inhibition of the endocannabinoid catabolic enzyme monoacylglycerol lipase (MAGL) decreases pain and inflammation caused by repeated morphine treatment. Male and female mice will be repeatedly administered morphine or vehicle, in the presence of increased endocannabinoid tone, for four days. Endocannabinoid tone will be increased by either chemical inhibition of MAGL, or genetic deletion of MAGL globally or on neurons only. Then, a small incision will be made and sutured closed in the plantar surface of one hindpaw, to model postoperative hyperalgesia. Mice will be tested repeatedly for pain- induced, pain-suppressed, and pain conditioning behavioral models. Endocannabinoid receptor mechanism will be determined using selective CB1 and CB2 cannabinoid receptor antagonists. Paw tissue will be collected to quantify proinflammatory cytokine levels, and individual cytokine levels will be correlated with pain-related behaviors. The anti-inflammatory mechanisms of endocannabinoid modulation will be further probed in vitro, using isolated macrophages/monocytes. Extant studies of preclinical OIH models have used male animals almost exclusively. Because women may be at increased risk for developing OIH, we will include sufficient numbers of both female and male mice to investigate Sex as a Biological Variable. In addition to increasing basic understanding of the underlying neural and immunological mechanisms that contribute to opioid-induced hyperalgesia, our translational research goal is to develop treatments for substance abuse disorders.
尽管有滥用的可能,阿片类药物仍然是一种黄金标准的镇痛药。小众之一

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Steven G. Kinsey其他文献

#74 Steroid resistance and anxiety-like behaviors develop in aged, socially defeated CD-1 mice
  • DOI:
    10.1016/j.bbi.2005.10.080
  • 发表时间:
    2005-07-01
  • 期刊:
  • 影响因子:
  • 作者:
    Steven G. Kinsey;Michael T. Bailey;John F. Sheridan;David A. Padgett
  • 通讯作者:
    David A. Padgett
Targeting Fatty Acid Amide Hydrolase (FAAH) to Treat Pain and Inflammation
  • DOI:
    10.1208/s12248-008-9075-y
  • 发表时间:
    2009-01-29
  • 期刊:
  • 影响因子:
    3.700
  • 作者:
    Joel E. Schlosburg;Steven G. Kinsey;Aron H. Lichtman
  • 通讯作者:
    Aron H. Lichtman
The synthetic cannabinoid agonist WIN 55,212-2 reduces experimental pruritus via CB<sub>2</sub> receptor activation
  • DOI:
    10.1016/j.neuropharm.2024.110216
  • 发表时间:
    2025-02-15
  • 期刊:
  • 影响因子:
  • 作者:
    Antonio Matt Reck;David P. Siderovski;Steven G. Kinsey
  • 通讯作者:
    Steven G. Kinsey

Steven G. Kinsey的其他文献

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{{ truncateString('Steven G. Kinsey', 18)}}的其他基金

Stemming the opioid-induced pain cascade via cannabinoid modulation
通过大麻素调节阻止阿片类药物引起的疼痛级联反应
  • 批准号:
    10435486
  • 财政年份:
    2021
  • 资助金额:
    $ 20.13万
  • 项目类别:
Reducing the deleterious effects of synthetic cannabinoid withdrawal on emotionality and motivation
减少合成大麻素戒断对情绪和动机的有害影响
  • 批准号:
    10134039
  • 财政年份:
    2020
  • 资助金额:
    $ 20.13万
  • 项目类别:
Endocannabinoid modulation of affective signs of cannabinoid withdrawal
内源性大麻素对大麻素戒断情感体征的调节
  • 批准号:
    8806670
  • 财政年份:
    2015
  • 资助金额:
    $ 20.13万
  • 项目类别:
Targeting multiple enzyme systems to reduce arthritic pain and inflammation
针对多种酶系统来减轻关节炎疼痛和炎症
  • 批准号:
    8878443
  • 财政年份:
    2015
  • 资助金额:
    $ 20.13万
  • 项目类别:

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