The role of the CB2 receptor and human CB2 receptor variants in neuropathic pain

CB2 受体和人类 CB2 受体变体在神经性疼痛中的作用

• 批准号: 62850903
• 负责人: Professor Dr. Andreas Zimmer
• 金额: --
• 依托单位: Institut für Molekulare Psychiatrie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/62850903?language=en
• 关键词: role; CB2; receptor; human; variants

Our previous research has indicated that CB2 receptors regulate inflammatory responses in the central nervous system after peripheral nerve injury by modulating the activity of microglia cells. Microglia activity is enhanced under neuropathic pain conditions in mice with a genetic deletion of the CB2 receptor encoding Cnr2 gene and enhanced in transgenic animals overexpressing this receptor. This project will investigate the molecular mechanisms that contribute to the enhanced microglia response. We will also address the possible involvement of other cells in the enhanced neuropathic pain phenotype of CB2-/- mice. For this purpose, we will establish mouse strains with a CB2 deletion in microglia, astrocytes and neurons using conditional CB2 knockout (CB2-/-) mice that were generated during the first funding period. The effects of the disruption of CB2 receptor signaling in these cells will be studied by analyzing the behavioral responses in animal models of inflammatory and neuropathic pain. We will also investigate molecular changes associated with these chronic pain conditions, which were also characterized during the first funding period. A further goal of this study is the functional analysis of human CB2 receptor variants in neuropathic pain. For this purpose we are in the process of establishing “humanized” mice, in which the mouse receptors is replaced with the human CB2 receptor variants.

我们以前的研究表明，CB 2受体通过调节小胶质细胞的活性来调节周围神经损伤后中枢神经系统的炎症反应。编码Cnr 2基因的CB 2受体基因缺失的小鼠在神经性疼痛条件下小胶质细胞活性增强，并且在过表达该受体的转基因动物中小胶质细胞活性增强。该项目将研究有助于增强小胶质细胞反应的分子机制。我们还将讨论其他细胞可能参与CB 2-/-小鼠增强的神经性疼痛表型。为此，我们将使用第一个资助期产生的条件性CB 2敲除（CB 2-/-）小鼠建立小胶质细胞、星形胶质细胞和神经元中CB 2缺失的小鼠品系。将通过分析炎症性和神经性疼痛动物模型中的行为反应来研究这些细胞中CB 2受体信号传导中断的影响。我们还将研究与这些慢性疼痛状况相关的分子变化，这些变化也是在第一个资助期内进行的。本研究的另一个目的是分析人CB 2受体变体在神经性疼痛中的功能。为此，我们正在建立“人源化”小鼠，其中小鼠受体被人CB 2受体变体取代。

项目成果

Crucial Role of CB2 Cannabinoid Receptor in the Regulation of Central Immune Responses during Neuropathic Pain

• DOI: 10.1523/jneurosci.3400-08.2008
• 发表时间: 2008-11-12
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Racz, Ildiko;Nadal, Xavier;Maldonado, Rafael
• 通讯作者: Maldonado, Rafael

Activation of cannabinoid 2 receptors protects against cerebral ischemia by inhibiting neutrophil recruitment

• DOI: 10.1096/fj.09-141275
• 发表时间: 2010-03-01
• 期刊: FASEB JOURNAL
• 影响因子: 4.8
• 作者: Murikinati, Sasidhar;Juettler, Eric;Schwaninger, Markus
• 通讯作者: Schwaninger, Markus

The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain

• DOI: 10.1016/j.euroneuro.2013.10.008
• 发表时间: 2014-04-01
• 期刊: EUROPEAN NEUROPSYCHOPHARMACOLOGY
• 影响因子: 5.6
• 作者: Klauke, A. -L.;Racz, I.;Zimmer, A.
• 通讯作者: Zimmer, A.

Interferon-γ Is a Critical Modulator of CB2 Cannabinoid Receptor Signaling during Neuropathic Pain

• DOI: 10.1523/jneurosci.3402-08.2008
• 发表时间: 2008-11-12
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Racz, Ildiko;Nadal, Xavier;Maldonado, Rafael
• 通讯作者: Maldonado, Rafael

The cannabinoid receptor type 2 (CNR2) gene is associated with hand bone strength phenotypes in an ethnically homogeneous family sample

• DOI: 10.1007/s00439-009-0708-8
• 发表时间: 2009-06
• 期刊: Human Genetics
• 影响因子: 5.3
• 作者: Meliha Karsak;I. Malkin;M. Toliat;C. Kubisch;P. Nürnberg;A. Zimmer;G. Livshits