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

Abstract

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) 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.

Analgesic Effects of Triterpenoid Saponins From Stauntonia chinensis via Selective Increase in Inhibitory Synaptic Response in Mouse Cortical Neurons

“…Glutamate and GABA systems were known to generate the opposite forces in neurotransmission and played key roles to the proper function of the CNS. Previous studies showed that α-asarone enhanced GABAergic neurotransmission but decreased glutamatergic release to restore the E/I balance and inhibit the chronic inflammatory pain induced by hind-paw injection of complete Freund’s adjuvant ( Tian et al, 2017 ). The expression level of cytoplasmic polyadenylation element binding protein 1 was reported to correlate to presynaptic E/I release in the regulation of chronic pain ( Yue et al, 2017 ).…”

How to study anxiety and depression in rodent models of chronic pain?

“…When conducted in an inflammatory pain model, a decrease in time spent in the centre of the OF is observed from one to 28 post‐induction days (Amorim et al, 2014; Chen et al, 2013; Gregoire, Wattiez, Etienne, Marchand, & Ardid, 2014; Guo et al, 2016; Kim et al, 2012; Parent et al, 2012; Sun et al, 2016; Tian et al, 2017; Yue et al, 2018; Table 2). Liu and collaborators tested anxiety‐like behaviours in the acid‐induced hyperalgesia model of fibromyalgia and observed an effect 13 days after induction (Liu et al, 2014; Table 3).…”

Tatarinan T, an α‐asarone‐derived lignin, attenuates osteoclastogenesis induced by RANKL via the inhibition of NFATc1/c‐Fos expression

“…Employed as a traditional Chinese medicine, the rhizome of Acorus tatarinowii Schott has low toxicity and is used to treat dementia, central nervous system‐associated disorders, rheumatosis, and other inflammatory diseases (Xu et al, ; Gao et al, ; Tian et al, ). Previous studies have investigated several extracts from Acorus tatarinowii Schott and found that the lignin‐like components, TO (Xu et al, ) and TN (Zhang et al, ), can both inhibit osteoclastogenesis; however, Tatarinan U (TU) and Tatarinan V (TV) lack this suppressive activity.…”