title: Huperzine A Alleviates Mechanical Allodynia but Not Spontaneous Pain via Muscarinic Acetylcholine Receptors in Mice.
abstract: Chronic pain is a major health issue and most patients suffer from spontaneous pain. Previous studies suggest that Huperzine A (Hup A), an alkaloid isolated from the Chinese herb Huperzia serrata, is a potent analgesic with few side effects. However, whether it alleviates spontaneous pain is unclear. We evaluated the effects of Hup A on spontaneous pain in mice using the conditioned place preference (CPP) behavioral assay and found that application of Hup A attenuated the mechanical allodynia induced by peripheral nerve injury or inflammation. This effect was blocked by atropine. However, clonidine but not Hup A induced preference for the drug-paired chamber in CPP. The same effects occurred when Hup A was infused into the anterior cingulate cortex. Furthermore, ambenonium chloride, a competitive inhibitor of acetylcholinesterase, also increased the paw-withdrawal threshold but failed to induce place preference in CPP. Therefore, our data suggest that acetylcholinesterase in both the peripheral and central nervous systems is involved in the regulation of mechanical allodynia but not the spontaneous pain.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China ; Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Zhen-Xing
authors.initials: ZX
authors.lastname: Zuo
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience and Collaborative Innovation Center for Brain Science, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience and Collaborative Innovation Center for Brain Science, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Yiner
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience and Collaborative Innovation Center for Brain Science, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Shu-Hao
authors.initials: SH
authors.lastname: Mei
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Maode
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience and Collaborative Innovation Center for Brain Science, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Xiang-Yao
authors.initials: XY
authors.lastname: Li
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000470:Alkaloids / Q000008:administration & dosage*; D000549:Ambenonium Chloride / Q000008:administration & dosage; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D001285:Atropine / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage; D059350:Chronic Pain / Q000517:prevention & control; D003000:Clonidine / Q000008:administration & dosage; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications; D007858:Learning / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D009437:Neuralgia / Q000517:prevention & control*; D017288:Pain Threshold / Q000187:drug effects; D010543:Peroneal Nerve / Q000293:injuries; D011976:Receptors, Muscarinic / Q000502:physiology*; D012717:Sesquiterpenes / Q000008:administration & dosage*
chemical_list: D000470:Alkaloids; D000700:Analgesics; D002800:Cholinesterase Inhibitors; D008070:Lipopolysaccharides; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D012717:Sesquiterpenes; C050426:huperzine A; D000549:Ambenonium Chloride; D001285:Atropine; D000110:Acetylcholinesterase; D003000:Clonidine