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Changes in Vanilloid Receptor 1 in Dorsal Root Ganglion in Rats with Imflammatory Pain-morphine Tolerance and Effects of MAPK Signal Pathway

Author: DongYing
Tutor: WangGuoLin
School: Tianjin Medical University
Course: Anesthesiology
Keywords: Inflammatory pain Morphine tolerance Capsaicin receptor Mitogen-activated protein kinase Extracellular signal-regulated Protein kinase p38 c-Jun N-terminal kinase
CLC: R96
Type: Master's thesis
Year: 2011
Downloads: 61
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Abstract


Clinical, long time given morphine and other opioid analgesics is a common means for the treatment of chronic pain and cancer pain, but long-term use of morphine tolerance phenomenon occurs, while limiting the clinical application of opioids. The capsaicin receptor nociceptors more and more attention [1,2]. Dorsal root ganglion there is a variety of the pain neurotransmitter nociceptors expression is an important part of the body of nociceptive information processing, integrating. Arthritis morphine tolerant rats in this study to establish the model as the basis to discuss the role of TRPV1 and TRPV1 in DRG plasticity changes in phosphorylation. In extracellular nociceptive pain transmission signal transduction information to the nucleus. Need the participation of intracellular signaling molecules, MAPK cascade effect is an important intracellular signal transduction system. In recent years, the MAPK signal transduction pathway of chronic pain signal transduction pathways and intracellular signaling molecules made some progress [3,4]. Therefore, this study from the point of view of the impact DRG plasticity changes explore the MAPK signal transduction pathway affect the causes and mechanisms of morphine tolerance and to explore methods to solve the problem of clinical morphine tolerance. First part: to establish the purpose of the rats with inflammatory pain - chronic morphine tolerance model and given the MAPK channel inhibitor model: the establishment of arthritis rat model of chronic morphine tolerance and composite the MAPK-channel inhibitor model to explore the MAPK signal transduction pathway of chronic morphine tolerance in arthritic rats formed. Methods: intrathecal tube successful adult male rats 45, were randomly divided into 9 groups (n = 5): Group A: CFA hind legs after inflammation intrathecal given 10μl saline, 1 to 2 times, continuous 7d; B Group: intrathecal morphine 10μg/kg (10 μl), 1 to 2 times a day for 7 successive days; C group: CFA hind legs after inflammation intrathecal single morphine 10μg/kg (10 μl); D group: CFA hind legs after inflammation intrathecal morphine 10μg/kg (10 μl), 1 to 2 times a day for 7 successive days; E group: A set of methods based on the day of the first administration 30min given 10μ125% DMSO; F groups: D group on the basis of daily 30 minutes before the first administration give% DMSO 10μ125; 30min G: D group method based on a day before the first dose given 10μg ERK1 / 2 inhibitor PD98059; group H: D-group method based on the day of the first administration 10μg p38 MAPK inhibitor SB203580; given 30min before I Group: D group on the basis of 30 minutes a day before the first administration given 50μgJNK inhibitor SP600125. Detect rat daily mechanical paw withdrawal threshold and hot plate paw withdrawal latency. Results: B, D, F, G, H, I group morphine tolerance phenomenon appears less than the group D, G, H, I group hyperalgesia extent. Conclusion: by intrathecal morphine repeatedly arthritic rats, can cause morphine analgesia tolerance rats with inflammatory pain. The three MAPK inhibitor formation of morphine tolerance in rats with inflammatory pain. Part II: inflammatory pain morphine tolerant rats dorsal root ganglion capsaicin receptor protein expression analysis and MAPK inhibitors purpose: TRPV1 and p-TRPV1 expression changes observed inflammatory pain - morphine tolerance in rat DRG at MAPK signal transduction pathway of its expression may explore morphine tolerance mechanisms and MAPK signal transduction pathway of morphine tolerance. Methods: The model, grouping and behavioral testing method with the first part. After the administration 7d L4 ~ L6DRG, rat DRG at TRPV1 and p-TRPV1 protein expression was measured using Werstern blot method. Results: B, D, F, G, H, I group of morphine tolerance phenomenon. Compared with the other seven groups, group D and group F TRPV1 and p-TRPV1 protein expression was highest. Conclusion: morphine tolerance TRPV1 and p-of TRPV1 the DRG protein; these three MAPK signal transduction pathway is involved in the formation of the rat chronic morphine tolerance.

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