title: Downregulation of spinal endomorphin-2 correlates with mechanical allodynia in a rat model of tibia cancer.
abstract: The endogenous tetrapeptide endomorphin-2 (EM2) participates in pain modulation by binding to pre- and/or post-synaptic μ opioid receptor (MOR). In the present study, pathological expression and antinociceptive effects of EM2 at the spinal level were investigated in a rat model of bone cancer pain. The model was established by introducing Walker 256 mammary gland carcinoma cells into the tibia medullary cavity. Immunohistochemical staining for EM2 showed a markedly reduced EM2-immunoreactivity in the ipsilateral spinal dorsal horn on days 6, 12 and 18 post Walker 256 inoculation (p < 0.05). Intrathecal injection (i.t.) of EM2 significantly attenuated cancer-induced mechanical allodynia (p < 0.05) which could be blocked by β-funaltrexamine (β-FNA), the μ receptor antagonist (p < 0.05). Furthermore, topical application of EM2 dose-dependently inhibited the electrically evoked C-fiber responses and postdischarge of wide dynamic range (WDR) neurons within the spinal cord (p < 0.05), and pretreatment with β-FNA abolished the hyperactivity of these neurons. Compared with the antinociception of morphine which took effect from 40 min to 100 min post application, the analgesic action of EM2 was characterized by quick onset and short-lived efficacy (p < 0.05), being most potent at 10 min and lasting about 20 min. These findings indicate that the down-regulated spinal EM2 is an important contributor to the neuropathological process of bone cancer pain and enhancing activation of EM2/μ receptor signaling might provide a therapeutic alternative to optimizing the treatment of cancer-induced bone pain.
authors.affiliation: Department of Anatomy, Histology and Embryology, K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China; Department of Ultrasound, Armed Police Tianjin Corps Hospital, Tianjin 300252,China.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pain Relief, Tianjin Key Laboratory of Cancer Prevention and Treatment, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Ultrasound, Armed Police Tianjin Corps Hospital, Tianjin 300252,China.
authors.forename: T
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: X-P
authors.initials: XP
authors.lastname: Mei
authors.affiliation: Department of Anatomy, Histology and Embryology, K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Anatomy, Histology and Embryology, K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Anatomy, Histology and Embryology, K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China. Electronic address: zfxmq@126.com.
authors.forename: F-X
authors.initials: FX
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Histology and Embryology, K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China. Electronic address: deptanat@fmmu.edu.cn.
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000700:Analgesics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001859:Bone Neoplasms / Q000150:complications*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors; D013977:Tibia
chemical_list: D000700:Analgesics; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105294:endomorphin 2; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine
keywords: allodynia; cancer-induced bone pain; endomorphin-2; morphine; nociceptive information transmission