Anxiolytic-like effects of α-asarone in a mouse model of chronic pain

• Published in: Metabolic brain disease Vol. 32; no. 6; pp. 2119 - 2129
• Main Authors: Tian, Jiao, Tian, Zhen, Qin, Shu-li, Zhao, Pu-yu, Jiang, Xun
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2017; Springer Nature B.V
• Subjects: Amygdala; Animals; Anisoles - pharmacology; Anisoles - therapeutic use; Anti-Anxiety Agents - pharmacology; Anti-Anxiety Agents - therapeutic use; Anxiety; Anxiety - complications; Anxiety - drug therapy; Anxiolytics; Asarones; Behavior, Animal - drug effects; Bioactive compounds; Biochemistry; Biological effects; Biomedical and Life Sciences; Biomedicine; Chronic pain; Chronic Pain - complications; Disease Models, Animal; Down-regulation; Excitability; Excitation; Glutamic acid receptors (ionotropic); Hyperalgesia - complications; Inflammation; Male; Metabolic Diseases; Mice; N-Methyl-D-aspartic acid receptors; Neurology; Neurons; Neurosciences; Oncology; Original Article; Pain; Pain perception; Pain Threshold - drug effects; Pyramidal cells; Receptors; Rodents; Treatment Outcome; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; γ-Aminobutyric acid A receptors; Anxiety; Amygdala; Synaptic transmission; α-Asarone; Chronic pain
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-017-0108-z

α-asarone (ASR) is a major bioactive compound isolated from the rhizome of Acorus tatarinowii Schott and it has extensive biological effects. Clinically, anxiety disorder is a common comorbidity of chronic pain. However, limited information is available regarding the effects of ASR on chronic pain-related anxiety. This study aims to evaluate the anxiolytic effects of ASR in chronic pain mice. Chronic inflammatory pain was induced by hind-paw injection of complete Freund’s adjuvant (CFA). Behavioral tests, western-blot analysis and whole-cell patch recordings were performed to evaluate the subsequent events. We found that ASR induced anxiolytic activities in CFA-injected mice but did not affect the nociceptive threshold. ASR administration reversed the up-regulation of GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, NR2A-containing N-methyl-D-aspartate (NMDA) receptors and down-regulation of γ-aminobutyric acid A (GABA A ) receptors in the basolateral amygdala (BLA) of CFA-injected mice. Electrophysiological data revealed that ASR treatment restored the balance between excitatory and inhibitory neurotransmissions, which was disturbed in the BLA of CFA-injected mice. Moreover, ASR prevented the hyper-excitability of pyramidal neurons in the BLA of chronic pain mice. Our results suggested that the anxiolytic effects of ASR were partially due to maintaining the balance between excitatory/inhibitory transmissions and attenuating neuronal hyper-excitability of excitatory neurons in the BLA.