title: Inhibition of Hyperpolarization-Activated Cation Current in Medium-Sized DRG Neurons Contributed to the Antiallodynic Effect of Methylcobalamin in the Rat of a Chronic Compression of the DRG.
abstract: Recently several lines of evidence demonstrated that methylcobalamin (MeCbl) might have potential analgesic effect in experimental and clinical studies. However, it was reported that MeCbl had no effect on treating lumbar spinal stenosis induced pain. Thus, the effects of short-term and long-term administration of MeCbl were examined in the chronic compression of dorsal root ganglion (CCD) model. We found that mechanical allodynia was significantly inhibited by a continuous application of high dose and a single treatment of a super high dose of MeCbl. Little is known about mechanisms underlying the analgesia of MeCbl. We examined the effect of MeCbl on the spontaneous activity (SA), the excitability, and hyperpolarization-activated nonselective cation ion current in compressed medium-sized dorsal root ganglion (DRG) neurons using extracellular single fiber recording in vivo and whole-cell patch clamp in vitro. We found that MeCbl significantly inhibited the SA of A-type sensory neurons in a dose-dependent manner and inhibited the excitability of medium-sized DRG neurons. In addition, MeCbl also decreased I h current density in injured medium-sized DRG neurons. Our results proved that MeCbl might exert an analgesic effect through the inhibition I h current and then might inhibit the hyperexcitability of primary sensory neurons under neuropathic pain state.
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Han
authors.affiliation: State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Department of Digestive Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Fancheng
authors.initials: F
authors.lastname: Meng
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiying
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Sanjue
authors.initials: S
authors.lastname: Hu
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000503:physiopathology*; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013117:Spinal Cord Compression / Q000150:complications; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; C019476:mecobalamin; D014805:Vitamin B 12