title: Gastrodin protects against chronic inflammatory pain by inhibiting spinal synaptic potentiation.
abstract: Tissue injury is known to produce inflammation and pain. Synaptic potentiation between peripheral nociceptors and spinal lamina I neurons has been proposed to serve as a trigger for chronic inflammatory pain. Gastrodin is a main bioactive constituent of the traditional Chinese herbal medicine Gastrodia elata Blume, which has been widely used as an analgesic since ancient times. However, its underlying cellular mechanisms have remained elusive. The present study demonstrated for the first time that gastrodin exhibits an analgesic effect at the spinal level on spontaneous pain, mechanical and thermal pain hypersensitivity induced by peripheral inflammation, which is not dependent on opioid receptors and without tolerance. This analgesia by gastrodin is at least in part mediated by depressing spinal synaptic potentiation via blockade of acid-sensing ion channels. Further studies with miniature EPSCs and paired-pulse ratio analysis revealed the presynaptic origin of the action of gastrodin, which involves a decrease in transmitter release probability. In contrast, neither basal nociception nor basal synaptic transmission was altered. This study revealed a dramatic analgesic action of gastrodin on inflammatory pain and uncovered a novel spinal mechanism that could underlie the analgesia by gastrodin, pointing the way to a new analgesic for treating chronic inflammatory pain.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.|Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an, 710032, China.|Department of Anesthesiology, Weifang People's Hospital, 151 Guangwen Road, Weifang, 261041, China.
authors.forename: Mei-Mei
authors.initials: MM
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.|Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Yu-Qi
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Wang
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Han
authors.affiliation: Class 2013, School of Clinical Medicine, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Rou-Gang
authors.initials: RG
authors.lastname: Xie
authors.affiliation: Class 2013, School of Clinical Medicine, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: San-Jue
authors.initials: SJ
authors.lastname: Hu
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Sheng-Xi
authors.initials: SX
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Ceng
authors.initials: C
authors.lastname: Luo
mesh_terms: D062646:Acid Sensing Ion Channel Blockers / Q000494:pharmacology*; D062565:Acid Sensing Ion Channels / Q000378:metabolism; D000698:Analgesia / Q000379:methods*; D000818:Animals; D001592:Benzyl Alcohols / Q000494:pharmacology*; D059350:Chronic Pain / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005960:Glucosides / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D013131:Spine / Q000378:metabolism* / Q000473:pathology; D055366:Synaptic Potentials / Q000187:drug effects*
chemical_list: D062646:Acid Sensing Ion Channel Blockers; D062565:Acid Sensing Ion Channels; D001592:Benzyl Alcohols; D005960:Glucosides; C045345:gastrodin