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The Efficacy and Mechanism of Diclofenac Sodium on the Neuropathic Pain in Rats
Author: YuCuiPing
Tutor: NiJiaZuo
School: Capital University of Medical Sciences
Course: Pain Medicine
Keywords: Diclofenac sodium Dorsal root ganglion Spinal dorsal horn Neuropathic pain Substance P Calcitonin gene-related peptide
CLC: R96
Type: Master's thesis
Year: 2007
Downloads: 126
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Abstract
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Objective To observe the different doses of diclofenac feeding on the sciatic nerve ligation (CCI) mechanical pain threshold in rats, dorsal root ganglia (DRG) and spinal cord dorsal horn P substance (SP) and calcitonin gene-related peptide (CGRP) expression and gastrointestinal the impact of the mucous membrane. Investigate the efficacy of oral diclofenac sodium for the treatment of neuropathic pain and possible mechanism of its gastrointestinal side effects, and to provide a reference for the clinical application of the drug. 40 Methods Male SD rats (body weight 240-260g), were randomly divided into the sciatic nerve ligation (CCI) group (32) and sham group (n = 8). CCI group is divided into: a: Diclofenac (2mg/kg group, n = 8; 4mg / kg group, n = 8; 10mg/kg group, n = 8); saline 1ml of the the b control group (N = 8). Since after eight days were given different doses of diclofenac sodium and saline twice daily for 7 days. Determination of mechanical stimulation using homemade Von-Frey cilia gavage before and gavage 1,3,5,7 L4-day rat right hind limb mechanical stimulation measured to flinching the threshold (PWMT) and 7 days after the medication immunohistochemical method 5 dorsal root ganglion cells and lumbar enlargement (L4-5 segment) at the spinal cord dorsal horn SP and CGRP expression, and in the light microscope to observe changes in the gastrointestinal mucosa structure. Results (1) mechanical pain threshold in CCI rats: the control group, 2mg/kg, 4mg/kg group, 10mg/kg group at each time point before treatment and after right hind limb PWMT with the sham group significantly lower (P lt; 0.01). Of 4mg/kg group compared to the drug on day 5,7 the right hindlimb PWMT with before treatment and control group was significantly increased (P lt; 0.01 or P lt; 0.05); each time point after the right hindlimb PWMT drug in the the 10mg/kg group of medication before and compared to the control group, a significant increase (P LT; 0.01). And showing a dose-dependent effect (P lt; 0.05). (2) the structure of the rat gastrointestinal mucosa: naked eye view of the rats antrum, glands and intestinal mucosa showed no ulceration and bleeding. Sham group, the control group biopsy view of the complete structure of the intestinal mucosa of the stomach, empty, no significant inflammatory cell infiltration. 2mg / k group biopsy concept of gastric mucosal glands slightly thickened; jejunum the glands no clear change. Gastric mucosal glands of 4mg/kg group concept fewer the gland wall thinning; intestinal villi fewer, shorter, decrease in goblet cells. 10mg/kg group concept gastric mucosal gland hyperplasia, thickening, stain darkens; intestinal villi fewer, shorter, intestinal eosinophils, inflammatory changes. (3) on rat dorsal root ganglia the festival (DRG) SP and CGRP expression: control group, 2mg/kg, 4mg/kg group, 10mg/kg group of SP and CGRP expression mean optical density (OD) of both significantly higher than the sham group (P lt; 0.01). The 4mg/kg group, 10mg/kg group average optical density (OD) of SP and CGRP expression was significantly lower than the control group (P lt; 0.01 or P lt; 0.05). (4) of the rat spinal cord dorsal horn I, Tier II SP, CGRP expression: control group, 2mg/kg, 4mg/kg, 10mg/kg group of SP and CGRP expression of the average optical density (OD) significantly higher than the sham group (P lt; 0.01). The 4mg/kg group, 10mg/kg group average optical density (OD) of SP and CGRP expression was significantly lower than the control group (P lt; 0.01 or P lt; 0.05). Conclusion 1, a certain dose (4 mg / kg, 10 mg / kg) of diclofenac sodium orally to alleviate the CCI rats mechanical hypersensitivity reaction, and a dose-dependent effect. Diclofenac sodium alleviate mechanical hyperalgesia mechanism may be the dorsal root ganglion and spinal cord dorsal horn of the SP, a decrease in the expression of CGRP. 3, although the analgesic effect of a dose-dependent effect, but the attendant side effects also increase prompted the clinical application of the dose should be strictly limited. Effective dose of diclofenac treatment of neuropathic pain can also cause damage to the gastrointestinal mucosa, therefore, is not an ideal drug for the treatment of neuropathic pain.
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