title: Inhibitory effect of spinal mGlu(5) receptor antisense oligonucleotide on the up-regulated expression of spinal G protein associated with chronic morphine treatment.
abstract: Knockdown of spinal metabotropic glutamate 5 (mGlu5) receptor was shown to inhibit the development of intrathecal morphine antinociceptive tolerance. The present work was designed to evaluate the expression of spinal G-protein during morphine tolerance and knockdown of spinal mGlu5 receptor with antisense oligonucleotide (ODN). Rats were treated with saline, morphine, mGlu5 receptor antisense or mismatch ODN intrathecally. Behavioral tests were employed to test the thermal and mechanical pain thresholds. Five days later, rats were scarified and spinal expression of spinal Gαi, Gαo, Gαq and Gβ were detected. Consistent with the previous results, knockdown of spinal mGlu5 receptor could inhibit spinal morphine antinociceptive tolerance in behavioral tests (P<0.05). The mGlu5 receptor antisense ODN produced a significant reduction in mGlu5 receptor protein of about 56.6% compared with the control group (P<0.05). Expression of spinal Gαi, Gαo, Gαq and Gβ were up-regulated while morphine tolerance developed (P<0.05). Antisense ODN of spinal mGlu5 receptor, but not mismatched ODN, reduced the spinal dorsal horn levels of Gαi, Gαo, Gαs, Gαq and Gβ (P<0.05). We conclude that expression of spinal G (αi, αo, αs, αq and β) protein may be up-regulated after chronic morphine treatment which could be attenuated by knockdown of spinal mGlu5 receptor with antisense ODN.
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yi Shan Road, Shanghai 200233, China.
authors.forename: Moxi
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yi Shan Road, Shanghai 200233, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yi Shan Road, Shanghai 200233, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yi Shan Road, Shanghai 200233, China.
authors.forename: Xiaqing
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yi Shan Road, Shanghai 200233, China. Electronic address: jiangw@sjtu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yi Shan Road, Shanghai 200233, China. Electronic address: balor@sjtu.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004361:Drug Tolerance / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D055785:Gene Knockdown Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology* / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000701:Analgesics, Opioid; C578937:Grm5 protein, rat; D016376:Oligonucleotides, Antisense; D064529:Receptor, Metabotropic Glutamate 5; D009020:Morphine; D019204:GTP-Binding Proteins
keywords: G protein; Intrathecal administration; Metabotropic glutamate receptor 5(mGlu(5) receptor); Morphine; Tolerance