title: Role of nitric oxide synthase in the development of bone cancer pain and effect of L-NMMA.
abstract: Spinal nitric oxide is involved in the mechanisms of pain generation and transmission during inflammatory and neuropathic pain. The aim of the present study was to explore the role of spinal nitric oxide in the development of bone cancer pain. 2 x 10(5) osteosarcoma cells were implanted into the intramedullary space of right femurs of C3H/HeJ mice to induce a model of ongoing bone cancer. Polymerase chain reaction and immunohistochemical analyses were performed to assess the expression of neuronal nitric oxide synthase (nNOS) and inducible (i)NOS in the spinal cord following inoculation. The results showed that inoculation of osteosarcoma cells induced progressive bone cancer, accompanied with pain-associated behavior. The levels of nNOS mRNA in the spinal cord of tumor mice began to increase at day 10 and then decreased to the level in sham mice at day 14, while iNOS mRNA markedly increased in the tumor group at days 10 and 14. Immunohistochemical analysis showed that nNOS- and iNOS-positive neurons were mainly located in the superficial dorsal horn and around the central canal of the L3-L5 spinal cord. Intrathecal injection of 50 µg NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) attenuated cancer-evoked pain behaviors at day 14. These findings indicated that an upregulation of nNOS and iNOS in the spinal cord is associated with bone cancer pain and suggests that exogenously administered L-NMMA may have beneficial effects to alleviate bone cancer pain.
authors.affiliation: Department of Anesthesiology, Affiliated Drum‑Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Affiliated Drum‑Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Affiliated Drum‑Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Affiliated Drum‑Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Yaguo
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology, Affiliated Drum‑Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Bo
authors.affiliation: Department of Anesthesiology, Affiliated Drum‑Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Affiliated Drum‑Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Affiliated Drum‑Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005269:Femur / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007278:Injections, Spinal; D051379:Mice; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics*; D012516:Osteosarcoma / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019323:omega-N-Methylarginine / Q000008:administration & dosage
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse