Involvement of cannabinoid type 1 receptor in fasting-induced analgesia.
Involvement of cannabinoid type 1 receptor in fasting-induced analgesia.
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DOI：
10.1177/1744806920969476
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发表时间：
2020-01
期刊：
影响因子：
3.3
通讯作者：
Oh SB
中科院分区：
文献类型：
--
作者：
Lee JY;Lee GJ;Nakamura A;Lee PR;Kim Y;Won CH;Furue H;Oh SB
已知内源性大麻素系统（ECS）不仅调节食物摄入，而且还调节疼痛，特别是通过在整个中枢神经系统和外周组织中表达的大麻素1型受体（CB 1 R）。我们先前的研究表明，禁食在成年雄性小鼠中产生镇痛作用，其通过腹膜内（i. p.）CB 1 R拮抗剂（SR 141716）给药。在本研究中，我们进一步研究了CB 1 R在外周组织中表达的作用。在福尔马林诱导的炎性疼痛模型中，腹腔注射外周限制性CB 1 R拮抗剂（AM 6545）可逆转禁食诱导的镇痛。然而，足底注射SR 141716不影响禁食诱导的镇痛作用。此外，CB 1 R的mRNA表达没有改变福尔马林模型禁食在背根神经节。福尔马林诱导的c-Fos在脊髓水平的表达不受禁食的影响，并在体内记录从浅背角的腰脊髓显示，禁食不影响福尔马林诱导的神经活动，这表明最小的参与脊髓禁食诱导的镇痛。最后，当我们进行迷走神经切断术以阻断来自胃肠（GI）系统的饥饿信号时，AM 6545不影响禁食诱导的镇痛，但SR 141716仍逆转禁食诱导的镇痛。综上所述，我们的研究结果表明，外周和中央CB 1 Rs有助于禁食诱导的镇痛作用和CB 1 Rs在胃肠道系统中的禁食信号传递到大脑，而不是在外周感觉神经元，可能有助于禁食诱导的镇痛作用。
The endocannabinoid system (ECS) is known to modulate not only food intake but also pain, especially via the cannabinoid type 1 receptor (CB1R) expressed throughout the central nervous system and the peripheral tissues. Our previous study demonstrated that fasting produces an analgesic effect in adult male mice, which is reversed by intraperitoneal (i.p.) administration of CB1R antagonist (SR 141716). In the present study, we further examined the effect of CB1R expressed in the peripheral tissues. In the formalin-induced inflammatory pain model, i.p. administration of peripherally restricted CB1R antagonist (AM 6545) reversed fasting-induced analgesia. However, intraplantar administration of SR 141716 did not affect fasting-induced analgesia. Furthermore, mRNA expression of CB1R did not change in the formalin model by fasting in the dorsal root ganglia. The formalin-induced c-Fos expression at the spinal cord level was not affected by fasting, and in vivo recording from the superficial dorsal horn of the lumbar spinal cord revealed that fasting did not affect formalin-induced neural activity, which indicates minimal involvement of the spinal cord in fasting-induced analgesia. Finally, when we performed subdiaphragmatic vagotomy to block the hunger signal from the gastrointestinal (GI) system, AM 6545 did not affect fasting-induced analgesia, but SR 141716 still reversed fasting-induced analgesia. Taken together, our results suggest that both peripheral and central CB1Rs contribute to fasting-induced analgesic effects and the CB1Rs in the GI system which transmit fasting signals to the brain, rather than those in the peripheral sensory neurons, may contribute to fasting-induced analgesic effects.
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影响因子：
3.3
作者：
Khasar, SG;Reichling, DB;Levine, JD
通讯作者：
Levine, JD
影响因子：
3.6
作者：
Gultekin, Fatih;Naziroglu, Mustafa;Cig, Bilal
通讯作者：
Cig, Bilal
DOI：
10.1126/science.aat5236
发表时间：
2018-09-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kaelberer MM;Buchanan KL;Klein ME;Barth BB;Montoya MM;Shen X;Bohórquez DV
通讯作者：
Bohórquez DV
影响因子：
2.9
作者：
Jang SP;Park SH;Jung JS;Lee HJ;Hong JW;Lee JY;Suh HW
通讯作者：
Suh HW
影响因子：
2.9
作者：
Becker S;Navratilova E;Nees F;Van Damme S
通讯作者：
Van Damme S