title: Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease.
abstract: In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) orα2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
authors.forename: Lei-Fang
authors.identifier: 0000-0001-7817-8464
authors.initials: LF
authors.lastname: Cao
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China; Suqian First Hospital, Suqian, Jiangsu 223800, China.
authors.forename: Xiao-Yan
authors.identifier: 0000-0001-8701-2423
authors.initials: XY
authors.lastname: Peng
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Ya
authors.identifier: 0000-0001-7020-8497
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Feng-Ming
authors.identifier: 0000-0002-1572-7750
authors.initials: FM
authors.lastname: Zhou
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Ruo-Xiao
authors.identifier: 0000-0002-3584-8576
authors.initials: RX
authors.lastname: Cheng
authors.affiliation: Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Chen
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
authors.forename: Wei-Feng
authors.identifier: 0000-0002-3594-1885
authors.initials: WF
authors.lastname: Luo
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Tong
authors.identifier: 0000-0001-9152-5264
authors.initials: T
authors.lastname: Liu
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage / Q000627:therapeutic use; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016627:Oxidopamine / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy*; D010300:Parkinson Disease / Q000188:drug therapy*; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects*
chemical_list: D001596:Benzylamines; D007980:Levodopa; D016627:Oxidopamine; C012102:DSP 4; D009638:Norepinephrine