Binge Ethanol Consumption Increases Inflammatory Pain Responses and Mechanical and Cold Sensitivity: Tigecycline Treatment Efficacy Shows Sex Differences.

Binge Ethanol Consumption Increases Inflammatory Pain Responses and Mechanical and Cold Sensitivity: Tigecycline Treatment Efficacy Shows Sex Differences.
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DOI:
10.1111/acer.13252
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发表时间:
2016-12
期刊:
Alcoholism, clinical and experimental research
影响因子:
--
通讯作者:
Guindon J
Guindon J
中科院分区:
其他
文献类型:
--
作者:
Bergeson SE;Blanton H;Martinez JM;Curtis DC;Sherfey C;Seegmiller B;Marquardt PC;Groot JA;Allison CL;Bezboruah C;Guindon J

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长期以来,医生一直报告慢性疼痛患者表现出更高的酒精使用障碍(AUD)倾向,AUD患者似乎具有更高的疼痛敏感性。本研究的目的是检验2个假设:(i)酗酒会增加炎性疼痛以及机械和冷敏感性;(ii)替加环素是酒精介导的疼痛行为和敏感性增加的有效治疗方法。使用雌性和雄性小鼠检验额外假设,即乙醇(EtOH)相关性状存在重要性别差异。评价“在黑暗中饮酒”(DID)酒精消耗和非饮酒对照、雌性和雄性、成年C57 BL/6 J小鼠的炎性疼痛行为以及机械和冷敏感性的存在。足底注射福尔马林(10 μl,2.5%生理盐水)产生炎性疼痛。对于冷感,使用20 μl丙酮滴。用电子vonFrey麻醉计测定机械性缩足阈。替加环素的疗效(80 mg/kg腹腔注射)以减少DID相关的疼痛反应和敏感性。 乙醇消耗增加炎症疼痛行为,同时也产生持续的机械和冷敏感性的女性和男性。替加环素在雄性动物中产生抗伤害效应;在福尔马林试验中,在雌性动物中观察到促伤害效应。同样,该药物降低了男性的机械和冷敏感性,但女性在这两项测试中表现出敏感性增加。我们的研究结果表明,酗酒会增加男女的疼痛、触觉和热感觉。此外,我们已经确定了替加环素对炎性疼痛以及机械和冷敏感性的性别特异性影响。开发替加环素作为AUD药物治疗可能需要考虑其在女性中的促伤害作用。需要进一步的研究来调查伤害感受性别特异性差异的机制。
Physicians have long reported that patients with chronic pain show higher tendencies for alcohol use disorder (AUD), and AUD patients appear to have higher pain sensitivities. The goal of this study was to test 2 hypotheses: (i) binge alcohol consumption increases inflammatory pain and mechanical and cold sensitivities; and (ii) tigecycline is an effective treatment for alcohol‐mediated‐increased pain behaviors and sensitivities. Both female and male mice were used to test the additional hypothesis that important sex differences in the ethanol (EtOH)‐related traits would be seen. “Drinking in the Dark” (DID) alcohol consuming and nondrinking control, female and male, adult C57BL/6J mice were evaluated for inflammatory pain behaviors and for the presence of mechanical and cold sensitivities. Inflammatory pain was produced by intraplantar injection of formalin (10 μl, 2.5% in saline). For cold sensation, a 20 μl acetone drop was used. Mechanical withdrawal threshold was measured by an electronic von Frey anesthesiometer. Efficacy of tigecycline (80 mg/kg i.p.) to reduce DID‐related pain responses and sensitivity was tested. DID EtOH consumption increased inflammatory pain behavior, while it also produced sustained mechanical and cold sensitivities in both females and males. Tigecycline produced antinociceptive effects in males; a pro‐nociceptive effect was seen in females in the formalin test. Likewise, the drug reduced both mechanical and cold sensitivities in males, but females showed an increase in sensitivity in both tests. Our results demonstrated that binge drinking increases pain, touch, and thermal sensations in both sexes. In addition, we have identified sex‐specific effects of tigecycline on inflammatory pain, as well as mechanical and cold sensitivities. The development of tigecycline as an AUD pharmacotherapy may need consideration of its pro‐nociceptive action in females. Further studies are needed to investigate the mechanism underlying the sex‐specific differences in nociception.
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