title: Clonidine depresses LTP of C-fiber evoked field potentials in spinal dorsal horn via NO-cGMP pathway.
abstract: Clonidine, a specific alpha2-adrenergic receptor agonist, has been found to be effective for the treatment of neuropathic pain, the mechanism underlying the effect is, however, not well understood. Here, the effect of clonidine on long-term potentiation (LTP) of C-fiber evoked field potentials in spinal dorsal horn, which is a synaptic model of injury-induced hyperalgesia, was investigated. LTP of C-fiber evoked field potentials was recorded in the superficial layers of spinal dorsal horn in anesthetized adult Sprague-Dawley rats. Clonidine and other substances were applied locally at the recording spinal segments before or after LTP induction by tetanic stimulation. We found that (1) Clonidine completely blocked LTP induction, when applied 30 min before tetanic stimulation and depressed spinal LTP, when applied 30 min and 3 h after LTP induction. (2) The inhibitory effect of clonidine on spinal LTP had two phases: a fast phase lasting for about 3.5 h and a slow phase persisting for the rest time of experiments (up to 8 h after drug). (3) Spinal clonidine at low dose (10.7 micro g/100 micro l) depressed spinal LTP but not C-fiber baseline response and at higher dose (107 micro g/100 micro l) depressed both of them. (4) Pretreatment with alpha2-adrenergic receptor antagonist yohimbine completely blocked the inhibitory effect of clonidine. (5) Pretreatment with muscarinic receptor antagonist atropine, nitric oxide synthesis inhibitor l-NNA or cGMP inhibitor ODQ depressed the fast phase inhibition significantly and abolished the slow phase inhibition completely. These results suggest that clonidine may exert analgesic effect by depressing the synaptic plasticity in spinal dorsal horn, via activation of muscarinic receptor-NO-cGMP pathway.
authors.affiliation: Pain Research Center, Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Yu-Xing
authors.initials: YX
authors.lastname: Ge
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Xin
authors.forename: Neng-Wei
authors.initials: NW
authors.lastname: Hu
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Ji-Tian
authors.initials: JT
authors.lastname: Xu
authors.forename: Xian-Guo
authors.initials: XG
authors.lastname: Liu
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003000:Clonidine / Q000494:pharmacology* / Q000627:therapeutic use; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018727:Muscarinic Antagonists; D018341:Receptors, Adrenergic, alpha-2; D009569:Nitric Oxide; D006152:Cyclic GMP; D003000:Clonidine