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GABAA Receptors in the Central Nucleus of the Amygdala Are Involved in Pain- and Itch-Related Responses

  • Long Chen
    Affiliations
    Ministry of Education Key Laboratory of Child Development and Disorders, and Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China
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  • Wei Wang
    Affiliations
    Ministry of Education Key Laboratory of Child Development and Disorders, and Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China
    Search for articles by this author
  • Tao Tan
    Affiliations
    Ministry of Education Key Laboratory of Child Development and Disorders, and Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China
    Search for articles by this author
  • Huili Han
    Affiliations
    Ministry of Education Key Laboratory of Child Development and Disorders, and Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China
    Search for articles by this author
  • Zhifang Dong
    Correspondence
    Address reprint requests to Zhifang Dong, PhD, 136 Zhongshan Er Road, Yuzhong District, Chongqing 400014, People Republic of China.
    Affiliations
    Ministry of Education Key Laboratory of Child Development and Disorders, and Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China
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Published:October 28, 2015DOI:https://doi.org/10.1016/j.jpain.2015.10.008

      Highlights

      • Activation of γ-aminobutyric acid type A (GABAA) receptors in the central nucleus of the amygdala (CeA) produce an antinociceptive effect.
      • Activation of GABAA receptors in the CeA inhibits an itch-related response.
      • Inactivation of GABAA receptors in the CeA enhances the itch-related response.

      Abstract

      Itch and pain are unpleasant sensations that distress many patients with disease. However, most studies have focused on the neural mechanisms of pain, and much less effort has been devoted to itch. It has been reported that itch and pain might share a common pathway, and γ-aminobutyric acid type A (GABAA) receptors in the central nucleus of the amygdala (CeA) are involved in pain modulation. However, the contribution of GABAA receptors in the CeA to the modulation of itch remains poorly understood. Herein, we report that bilateral intra-CeA microinjection of a selective GABAA receptor agonist muscimol hydrochloride (Mus; 50 ng per side), but not a selective GABAA receptor antagonist bicuculline (Bic; 20 ng per side) or vehicle, showed significant analgesic effects, reflected by an increase in tail-flick latency and a decrease in allyl isothiocyanate (mustard oil)–evoked ipsilateral forelimb wipes. More importantly, rats subjected to intra-CeA infusion of Bic showed a significantly greater number of scratching bouts and time in acute and chronic pruritus animal models than control rats. Conversely, intra-CeA infusion of Mus in animal models dramatically decreased the number of scratching bouts and time compared with control rats. In addition, intra-CeA infusion of Bic or Mus at the current dose had no obvious effects on other behaviors including locomotor activity and spontaneous facial grooming in rats subjected to cheek microinjection of 5-hydroxytryptamine. Taken together, these results indicate that the GABAA receptor–mediated inhibitory system in the CeA is involved in itch modulation as well as is known in pain control.

      Perspective

      Itch, especially chronic itch, remains a challenge in clinic. Results of this study showed that the GABAA receptors in the CeA play an important role in itch modulation, which might help us to better understand the mechanisms of itch and subsequently develop novel mechanisms-based strategies to treat chronic itch in clinic.

      Key words

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