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

alpha-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 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, NR2A-containing N-methyl-D-aspartate (NMDA) receptors and down-regulation of gamma-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.