Involvement of ryanodine receptors in tetanic sciatic stimulation-induced long-term potentiation of spinal dorsal horn and persistent pain in rats.
Tetanic stimulation of the sciatic nerve induces long-term potentiation (LTP) of C-fiber-evoked field potentials in the spinal dorsal horn and persistent pain, suggesting that spinal LTP may be a substrate for central sensitization of the pain pathway. However, its cellular mechanism remains unclear. The present study provides electrophysiological and behavioral evidence for the involvement of ryanodine receptor (RyR) in the induction of spinal LTP and persistent pain in rats. The specific inhibitor of ryanodine receptor, ryanodine and dantrolene, dose dependently blocked the induction, but not maintenance, of spinal LTP and reduced persistent pain behaviors induced by tetanic sciatic stimulation. Both cyclic ADP ribose (cADPR), an endogenous agonist of RyR, and (±)-1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester (Bay K 8644), an agonist of L-type calcium channel, attenuated ryanodine-induced inhibition. Immunohistochemistry and electron microscopic observation showed that RyR subtypes RyR1 and RyR3 were located in the spinal dorsal horn. The results suggest that RyRs are involved in synaptic plasticity of the spinal pain pathway and may be a novel target for treating pain. © 2012 Wiley Periodicals, Inc.
Institute of Neurobiology, Institutes of Brain Science and State Key laboratory of Medical Neurobiology, Fudan University, Shanghai, China. ninglu@fudan.edu.cn
Ning
N
Lü
Long-Zhen
LZ
Cheng
Yu-Qiu
YQ
Zhang
Bai-Chang
BC
Lü
Yun-Qing
YQ
Li
Zhi-Qi
ZQ
Zhao
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D002120:Calcium Channel Agonists / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000009:adverse effects; D005071:Evoked Potentials / Q000502:physiology; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D010146:Pain / Q000209:etiology / Q000473:pathology*; D010147:Pain Measurement; D020671:Posterior Horn Cells / Q000503:physiopathology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology*
D002120:Calcium Channel Agonists; D009125:Muscle Relaxants, Central; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D003620:Dantrolene