Reduced activity of adenylyl cyclase 1 attenuates morphine induced hyperalgesia and inflammatory pain in mice.
Reduced activity of adenylyl cyclase 1 attenuates morphine induced hyperalgesia and inflammatory pain in mice.
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DOI：
10.3389/fphar.2022.937741
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发表时间：
2022
影响因子：
5.6
通讯作者：
Klein, Amanda H.
中科院分区：
文献类型：
--
作者：
Johnson, Kayla;Doucette, Alexis;Edwards, Alexis;Verdi, Aleeya;McFarland, Ryan;Hulke, Shelby;Fowler, Amanda;Watts, Val J.;Klein, Amanda H.
阿片耐受、阿片诱导的重复给药痛敏和慢性疼痛与腺苷酸环化酶活性上调有关。本研究的目的是测试的假设，腺苷酸环化酶1（AC 1）的活性或表达的减少会减弱吗啡耐受性和超敏反应，和炎症疼痛使用小鼠模型。为了研究阿片耐受性和阿片诱导的痛觉过敏，使用静态（15 mg/kg，5天）或递增耐受性范例（10-40 mg/kg，4天）对小鼠进行盐水或吗啡每日两次治疗。AC 1抑制剂ST 03437（2.5-10 mg/kg，IP）全身治疗可减少小鼠中吗啡诱导的痛觉过敏。与对照小鼠相比，腰椎鞘内给予包含靶向Adcy 1的短发夹RNA的病毒载体可降低吗啡诱导的超敏反应。与此相反，急性吗啡镇痛，沿着热爪回缩lavage，运动性能，在一个开放的领域测试中的探索，和挖洞行为不受鞘内Adcy 1敲低。通过鞘内注射敲低Adcy 1也降低了炎性机械性痛觉过敏，并在注射后一周足底注射完全弗氏佐剂（CFA）后增加了穴居和筑巢活动。
Opioid tolerance, opioid-induced hyperalgesia during repeated opioid administration, and chronic pain are associated with upregulation of adenylyl cyclase activity. The objective of this study was to test the hypothesis that a reduction in adenylyl cyclase 1 (AC1) activity or expression would attenuate morphine tolerance and hypersensitivity, and inflammatory pain using murine models. To investigate opioid tolerance and opioid-induced hyperalgesia, mice were subjected to twice daily treatments of saline or morphine using either a static (15 mg/kg, 5 days) or an escalating tolerance paradigm (10–40 mg/kg, 4 days). Systemic treatment with an AC1 inhibitor, ST03437 (2.5–10 mg/kg, IP), reduced morphine-induced hyperalgesia in mice. Lumbar intrathecal administration of a viral vector incorporating a short-hairpin RNA targeting Adcy1 reduced morphine-induced hypersensitivity compared to control mice. In contrast, acute morphine antinociception, along with thermal paw withdrawal latencies, motor performance, exploration in an open field test, and burrowing behaviors were not affected by intrathecal Adcy1 knockdown. Knockdown of Adcy1 by intrathecal injection also decreased inflammatory mechanical hyperalgesia and increased burrowing and nesting activity after intraplantar administration of Complete Freund’s Adjuvant (CFA) one-week post-injection.
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影响因子：
3.3
作者：
Liu RH;Shi W;Zhang YX;Zhuo M;Li XH
通讯作者：
Li XH
影响因子：
4.3
作者：
Griggs RB;Laird DE;Donahue RR;Fu W;Taylor BK
通讯作者：
Taylor BK
DOI：
10.1007/s12630-009-9149-z
发表时间：
2009-10-01
期刊：
CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE
影响因子：
--
作者：
Liou, Jiin-Tarng;Liu, Fu-Chao;Lui, Ping-Wing
通讯作者：
Lui, Ping-Wing
影响因子：
3.6
作者：
Andrews, N.;Legg, E.;Rice, A. S. C.
通讯作者：
Rice, A. S. C.
影响因子：
7.3
作者：
Brust, Tarsis F.;Alongkronrusmee, Doungkamol;Watts, Val J.
通讯作者：
Watts, Val J.