title: Antinociceptive Profile of Levo-tetrahydropalmatine in Acute and Chronic Pain Mice Models: Role of spinal sigma-1 receptor.
abstract: We have recently reported that repeated systemic treatments of extract from Corydalis yanhusuo alleviate neuropathic pain and levo-tetrahydropalmatine (l-THP) is one of active components from Corydalis. We designed this study to investigate antinociceptive effect of l-THP in acute and chronic pain models and related mechanism within the spinal cord. We found that intraperitoneal pretreatment with l-THP significantly inhibited the second phase of formalin-induced pain behavior. In addition, intrathecal as well as intraperitoneal pretreatment with l-THP reduced the mechanical allodynia (MA) induced by direct activation of sigma-1 receptor (Sig-1). In chronic constriction injury mice, these treatments remarkably suppressed the increase in MA and spinal phosphorylation of the NMDA receptor NR1 subunit expression on day 7 after surgery. Intrathecal treatment with l-THP combined with the Sig-1R antagonist, BD1047 synergistically blocked MA suggesting that l-THP modulates spinal Sig-1R activation. CatWalk gait analysis also supported that antinociceptive effect of l-THP as demonstrated by restoration of percentages of print area and single stance. Meanwhile, intrathecal pretreatment with naloxone, non-selective opioid receptor antagonist, did not affect the effect of l-THP. In conclusion, these results demonstrate that l-THP possesses antinociceptive effects through spinal Sig-1R mechanism and may be a useful analgesic in the management of neuropathic pain.
authors.affiliation: Department of Physiology and Medical Science, College of Medicine and Brain Research Institute, Chungnam National University, Daejeon 35015, South Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kang
authors.affiliation: KM Fundamental Research Division Korea Institute of Oriental Medicine, Daejeon 34054, South Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Moon
authors.affiliation: Department of Physiology and Medical Science, College of Medicine and Brain Research Institute, Chungnam National University, Daejeon 35015, South Korea.
authors.forename: Jae-Gyun
authors.initials: JG
authors.lastname: Choi
authors.affiliation: KM Fundamental Research Division Korea Institute of Oriental Medicine, Daejeon 34054, South Korea.
authors.forename: Suk-Yun
authors.initials: SY
authors.lastname: Kang
authors.affiliation: KM Fundamental Research Division Korea Institute of Oriental Medicine, Daejeon 34054, South Korea.
authors.forename: Yeonhee
authors.initials: Y
authors.lastname: Ryu
authors.affiliation: Department of Physiology and Medical Science, College of Medicine and Brain Research Institute, Chungnam National University, Daejeon 35015, South Korea.
authors.forename: Jin Bong
authors.initials: JB
authors.lastname: Park
authors.affiliation: Department of Veterinary Physiology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826, South Korea.
authors.forename: Jang-Hern
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Physiology and Medical Science, College of Medicine and Brain Research Institute, Chungnam National University, Daejeon 35015, South Korea.|Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-0625, USA.
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Kim
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology*; D059350:Chronic Pain / Q000378:metabolism* / Q000628:therapy*; D005029:Ethylenediamines / Q000494:pharmacology; D005557:Formaldehyde; D005786:Gene Expression Regulation; D006930:Hyperalgesia / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000494:pharmacology; D009437:Neuralgia / Q000378:metabolism; D059408:Pain Management; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D017480:Receptors, sigma / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D000097605:Sigma-1 Receptor
chemical_list: D000700:Analgesics; D001600:Berberine Alkaloids; D005029:Ethylenediamines; D005557:Formaldehyde; D009270:Naloxone; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C409466:NR1 NMDA receptor; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; C014215:tetrahydropalmatine