TY - JOUR
T1 - Binge Ethanol Consumption Increases Inflammatory Pain Responses and Mechanical and Cold Sensitivity
T2 - Tigecycline Treatment Efficacy Shows Sex Differences
AU - Bergeson, Susan E.
AU - Blanton, Henry
AU - Martinez, Joseph M.
AU - Curtis, David C.
AU - Sherfey, Caitlyn
AU - Seegmiller, Brandon
AU - Marquardt, Patrick C.
AU - Groot, Jessica A.
AU - Allison, Clayton L.
AU - Bezboruah, Christian
AU - Guindon, Josée
N1 - Funding Information:
We thank Dr. Deb Finn for assistance with manuscript preparation and editing. We thank NIAAA R21 AA021142 (SEB), the Bryan C. Miller, Jr. and Martha H. Miller Foundation, Inc., The CH Foundation (JG) and Texas Tech University Health Sciences Center School of Medicine 121035 (JG) and the resources/facilities used at the Texas Tech University Health Sciences Center (SEB, JG) for their support. The authors state that no one has a conflict of interest.
Publisher Copyright:
Copyright © 2016 The Authors Alcoholism: Clinical and Experimental Research published by Wiley Periodicals, Inc. on behalf of Research Society on Alcoholism.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Background: 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. Methods: “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. Results: 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. Conclusions: 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.
AB - Background: 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. Methods: “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. Results: 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. Conclusions: 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.
KW - Alcohol
KW - Alcohol Use Disorder
KW - Ethanol
KW - Mechanical and Cold Sensitivities
KW - Pain Sensitivity
KW - Tigecycline
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U2 - 10.1111/acer.13252
DO - 10.1111/acer.13252
M3 - Article
C2 - 27862022
AN - SCOPUS:84999864944
SN - 0145-6008
VL - 40
SP - 2506
EP - 2515
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
IS - 12
ER -