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Experimental Study of the Preventive Effect of Parecoxib on Allodynia of Spinal Cord

Author: ZengYanRu
Tutor: ZuoShouZhang
School: Guangzhou Medical College
Course: Anesthesiology
Keywords: Parecoxib Incisional pain Mechanical paw withdrawal threshold Tail flick response latency Prostaglandin E2 Cyclooxygenase Central sensitization Microdialysis
CLC: R965
Type: Master's thesis
Year: 2011
Downloads: 32
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Abstract

Background parecoxib (Parecoxib, Par) is a highly selective cyclooxygenase-2 inhibitors, intravenous quickly liver carboxylic acid esterase hydrolysis into valdecoxib, by specific inhibition of the epoxy together enzyme -2 blocking arachidonic acid synthesis of prostaglandins exert anti-inflammatory and analgesic effects. Parecoxib 2002, approved in the European market, be allowed to be listed in China in 2008, as the world's first injectable selective cyclooxygenase-2 inhibitors, NSAIDs were associated with the development of a milestone. But its analgesic effect of parecoxib has been put into clinical use, is often considered the main peripheral rarely reported, and its central inhibition effect and mechanism of allodynia. Cyclooxygenase (Cyclooxygenase, COX) in arachidonic acid (Arachidonic acid, AA) is the rate-limiting enzyme in the pathway substrate generates prostaglandins (PGs). COX contains two subtypes, namely COX-1 and COX-2. COX-1 is the normal component of the body, were expressed in most tissues, usually produces prostaglandins, substances in order to meet the ongoing physiological process requires, also known as structure-type enzyme; COX-2 cells rarely under normal circumstances, inflammatory stimuli and cytokines which may be induced to express its catalytic prostaglandins produced with pain, inflammation reaction, also known as induction-type enzyme. The prostaglandin E ₂ (Prostaglandin E ₂, PGE ₂), arachidonic acid metabolites in the role of cyclooxygenase, an important inflammation and promote injury medium plays an important role in the peripheral and central sensitization. In the local area of ??the injury, PGE ₂ to reduce the pain threshold, activation of peripheral pain receptors sensitive Outsider weeks nociceptive afferent fibers in the spinal cord but also synthesis and release of PGE ₂ increase dorsal root excitability of neurons, resulting in hyperalgesia. Studies have shown that, in the base case of spinal cord COX-1 and COX-2, and noxious stimuli in the spinal cord PGE ₂ increased rapidly. This topic Brennan incision pain model application behavior measurement microdialysis ELISA and immune staining method to observe the process of the formation and development of post-operative pain Parecoxib rat incisional pain analgesic effect and spinal cord level PGE ₂ and COX two subtypes (COX-1 and COX-2) expression of pain caused by substances explore the inhibitory effect of parecoxib in postoperative pain caused allodynia and mechanisms. The first part Parecoxib purpose of the analgesic effect of incision pain in rats to explore of Parecoxib analgesic effects of incision pain in rats, and preemptive analgesia effect. Methods 40 male Wistar rats, weighing 250 ~ 350g, were randomly divided into four groups, respectively, for the control group (C), the surgery group (P ₀ group), preemptive analgesia group (P the ₁ group) postoperative analgesia group (P ₂ group), 10 in each group. Control group (C group) only intravenous injection of 0.9% saline 2ml, 15min after inhalation of 2% isoflurane not Brennan incision pain surgery; surgery group (P ₀ group) intravenous injection of 0.9% saline 2ml , 15min after inhalation of 2% isoflurane the ether line Brennan incision pain surgery; preemptive analgesia group (P ₁ group) intravenous parecoxib 5mg/kg, 15min after inhalation of 2% isoflurane line Brennan the incision pain patients; postoperative analgesia group (P ₂ group) inhalation of 2% isoflurane Brennan incision pain surgery, end of surgery, intravenous parecoxib 5mg/kg. To von Frey instrument of dolorimeter and tail flick dolorimeter measured incisional pain preoperative 30min and postoperative 1h, 2h, 3h, 4h, 5h and 6h mechanical paw withdrawal threshold (MWT) and thermal tail flick response latency (TFL) . 1, mechanical paw withdrawal reflex threshold (MWT) changes in rats MWT basis of value basically the same (P gt; 0.05). C group at each time point MWT change (P gt; 0.05), maintained at (14.52 ^{1 4.76) g; ₀ group after incisional pain MWT (14.82 ± 0.48) g significantly lower (4.93 ± 0.48) g, 2h and reached the lowest value (74.49%) is lower than the underlying value, and subsequently recovered slightly, but still significantly lower than at the same time point control group C; P _{1 < / sub> group postoperative MWT slightly reduced, but the reduction is gentle, fluctuations in (10.84 ^{1 1.96) g, postoperative MWT in of postoperative least 2h decline (11.96 ± 0.35 g), only than the basis of the value of reducing 18.92%; P ₁ group and P ₂ group after each time point MWT were significantly higher than P ₀ group (P lt P ₁ group and P ₂ group; 0.05);, after 1h MWT was no significant difference (P gt; 0.05), after 2 ^{6 < / sup> h P ₁ group MWT was significantly higher than the P ₂ group (P lt; 0.05). 2, thermal drift response latency (TFL) changes in the four groups of rats the TFL the basis of the value of the basic same (P gt; 0.05). Small changes of TFL Group C at each time point (P gt; 0.05), maintained at (3.72 ^{3 .84) s; ₀ group postoperative TFL (3.76 ± 0.36) s significantly lower (1.89 ± 0.17) s, 2h and reached the lowest value (73.40%) compared with baseline, and then recovered slightly, but still significantly lower than at the same time point control group C; P ₁ group after TFL slightly lower, but the reduction is gentle, fluctuations in (2.12 ^{3 .03) s, TFL least 2h decline after surgery (3.03 ± 0.09s), only than the basic value 20.26%; reduction after P ₁ group and P ₂ group at each time point the TFL were significantly higher than P ₀ group (P lt; 0.05 , group and P _{,,); P ₁ 2} group after 1h TFL was no significant difference (P gt; 0.05), postoperative 2 ^{6 h P ₁ group TFL significantly higher than P ₂ group (P lt; 0.05). Conclusion Parecoxib incision pain in rats with good analgesic effect, and demonstrate a clear preemptive analgesia effect. The second part Parecoxib spinal level of prostaglandin E ₂ and cyclooxygenase Objective To observe the process of the formation and development of post-operative pain Parecoxib rat spinal cord levels of PGE ₂ and COX-1 and COX-2 expression and to explore the effect and mechanism of parecoxib in postoperative pain caused allodynia. The method of selection of successful indwelling 40 the microdialysis probes male Wistar rats, weighing 250 ~~ 350g, were randomly divided into four groups, namely the control group (C group), the surgery group (P ₀ group) preemptive analgesia group (P ₁ group), postoperative analgesia group (P ₂ group), 10 in each group. Control group (C) not only intravenous injection of 0.9% saline 2ml, 15min Brennan incision pain surgery; surgery group (P ₀ group) intravenous injection of 0.9% saline 2ml, 15min underwent Brennan incision pain surgery; preemptive analgesia group (P ₁ group) intravenous parecoxib 5mg/kg 15min underwent Brennan incision pain surgery; postoperative analgesia group (P ₂ group) line the Brennan incision pain surgery, intravenous parecoxib 5mg/kg the end of surgery. Brennan incisional pain preoperative 30min basis of the value of the sample collection line microdialysis technique 30min after start every the 30min collect samples once collected six hours per tube samples are 150μl, dialysate collected at -80 ° C refrigerator, followed by ELISA PGE ₂ concentration; rat lumbar spinal cord taken after 6 hours after infusion, using immunohistochemical determination of changes in the lumbar spinal cord COX-1 and COX-2 expression. 1, spinal cord dorsal horn PGE ₂ concentration in rat spinal cord dorsal horn PGE ₂ underlying value is basically the same (P gt; 0.05), respectively (153.08 ± 2.07 ) pg / ml, (153.06 ± 2.29) pg / ml, (154.17 ± 1.78) pg / ml, (154.38 ± 1.61) pg / ml. C group at each time point the PGE ₂ small changes (P gt; 0.05), fluctuations in (153.03 ^{1 54.66) pg / ml. P ₀ group the postoperative of PGE ₂ sharp increase in postoperative the 120min reached peak (4.63 times higher than the underlying value), followed by a slow decline, after 360min PGE ₂ still 82.47% higher than the C group. Compared with C group, P ₁ group and P ₂ group PGE ₂ slightly elevated postoperative 30min, respectively (187.79 ± 10.88) pg / ml and (190.82 ± 10.54) pg / ml; P _{of PGE ₁ Group 2} 60min began after lower than in group C, the postoperative the 120min lowest value ( lower than at the same time point group C 43.18%), followed by a slow rise, postoperative the 360min still significantly lower than the C group (P lt; 0.05); P ₂ group PGE ₂ surgery lower than in group C after 60min, the postoperative 240min rise to similar to the C group (P gt; 0.05), followed by higher than C group. P ₀ group, P ₁ group and P ₂ group after each time point PGE ₂ were significantly lower (P lt; 0.05). The P ₁ group and P ₂ group, postoperative 90min of PGE ₂ concentrations were similar (P gt; 0.05), P the Group of PGE ₂ from the postoperative 120min began significantly lower than P ₂ group (P lt; 0.05), and continued into the postoperative 360min. 6h after spinal cord levels of COX-1 and COX-2 immunoreactive cells change in group C rat lumbar spinal cord COX-1 and COX-2 immunoreactive cells have a small amount of expression, chromatin shallow, COX-1 and COX- 2 immunohistochemical staining score lower (3.29 ± 1.86 and 2.78 ± 2.05, respectively). Compared with C group, P ₀ group P ₁ group and P ₂ group of COX-1 and COX-2 expression was significantly increased immunoreactive cells mainly concentrated in the spinal cord dorsal horn Ⅰ ^{Ⅱ lamellar deeply stained, COX-1 and COX-2 immunohistochemical staining score was significantly higher than that in group C (P lt; 0.05). P ₀ group P ₁ group and P ₂ group expression of COX-1 and COX-2 immunoreactive cells similar, COX-1 and COX -2 immunohistochemical staining score was no significant difference (P gt; 0.05). P ₀ group P ₁ group and P ₂ group immunoreactive cells in the expression of COX-2 more than COX-1 immunoreactive cells express The dyeing deeper. Conclusion Parecoxib not inhibit spinal dorsal horn expression of cyclooxygenase, but can effectively inhibit COX-2, thereby inhibiting the spinal level after PGE ₂ rise to play Inhibition of Central pain hypersensitivity.}}}}}}}}}

Experimental Study of the Preventive Effect of Parecoxib on Allodynia of Spinal Cord

Abstract

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