The Comparison Of The Preemptive Analgesia Efficacy Of Ketamine Or Tramadol On Hyperalgesia In Rats Induced By Capsaicin

Objective:Capsaicin the beginning of the subjects will have a strong pain experience,and with short-term pain thermal and mechanical hyperalgesia(Culp etal.1989:LaMotte et al,1991; Sakurada et al.1992).Capsaicin,a C-fiber selected nevous blockade which generated excitement-inhibition dual role.Early application of capsaicin Caused pain with the neuropeptide release.Capsaicin may cause the release of substance P and directly stimulate nerve cells to produce some of the non-inflammatory chemokines which involved in inflammatory response.Substance P is recognized as the primary neurotransmitter neurons that can stimulate higher levels of pain transmission neurons upward,it play an important role in the pain transmission of spinal cord which exists in the spinal cord RexedⅠandⅡlayer of the Aδfibers and C fibers, continued electrical,thermal,chemical,and other peripheral nociceptive stimulation of these fibers can cause spinal dorsal horn of the release of substance P.The dorsal horn of the spinal cord significantly increased substance P.Since the beginning of the hyperalgesia The clinical application of capsaicin to be restricted, how to eliminate the side effects,especially excitatory stimulus, whether capsaicin for the nerve root,stem side to relieve the pain. Early application of capsaicin can produce hyperalgesia,while what kind of drugs has the effect of preemptive analgesia,what kind of drugs is better and accepted by the clinical,people have been trying to find effective solutions for these problems.Through the establishment of hyperalgesia in epidural space of rats induced by capsaicin,to observe the behavioral response to noxious stimulation, and determin the changes of pain threshold and Substance P to compare the changes in preemptive analgesia caused by capsaicin.Methods:Healthy male Wistar rats 54 Which 48 rats were randomly divided into 3 groups(InⅠ,Ⅱ,Ⅲrats at different time points after the determination of the pain threshold.Respectively, in each group were randomly selected two of the other six rats, total 12 were used to the experiment of immunohistochemistry), each with 16,saline 100μl+1%capsaicin 100μl(Ⅰ),5 mg ketamine(5 percent ketamine 100μl)+1%Capsaicin 100μl(Ⅱ), 5 mg tramadol(5%Tramadol 100μl)+1%capsaicin 100μl(Ⅲ). Immunohistochemistry was used to test the 12 rats were randomly divided into three groups,each with four.Under deep anesthesia, epidural catheter is placed,then inject saline 100μl,5%of ketamine 100μl,5%of tramadol 100μl respectively,10min later inject 1%capsaicin 100μl into cavitas epiduralis separately.The rats were observed and recorded the behavioral response to noxious stimulation and duration in initial injection of capsaicin(5 min). Determine pain threshold after 5 min,15min,60min,90min, 120min,180min with Hot Sounds law.Capsaicin given after five minutes,respectively,from A,B,C,the two rats under deep anesthesia based reperfusion.After 180 minutes to capsaicin, respectively,from A,B,C,the two rats under deep anesthesia infusion of material by slicing and the SABC method SP immunohistochemical reaction.Results are analysisde with the LUZEX-F image system,the area of SP immunoreactive substances of each slice is determinded(ten sections,from the mean; units:positive units).Results:This study,5 percent of ketamine and 5%tramadol rats is injected respectively into epidural space of rats.After 1 percent capsaicin is injected,we observe that the thermal pain threshold decreased 5 minutes after administration.Then after going through a period of increased gradually decline,capsaicin given after the rats experienced pain-sensitive period and the period of desensitization,at a time,the pain threshold of groupⅡand groupⅢis higher than groupⅠ(P＜0.05).Each group the rate of the pain threshold is increased 15 min later,then declined,whileⅡ,Ⅲgroup the changes of pain threshold is similar in 60 min(P＞0.05).60min later,the groupⅡis always higher than groupⅢ(P＜0.05).Pain threshold three groups showed a significant change statistically significant.From the analysis of the Substance P in granting capsaicin 5 min and 180 min.A group of substance P in rats experienced a decrease from up to the process,capsaicin given after the rats experienced pain-sensitive period and the period of desensitization,hyperalgesia in the period,capsaicin caused the massive release of substance P and desensitization in the period,the nerve fibers of capsaicin caused depletion of substance P that Resulted in reduction of substance P.The group A and group C compared with group B rat spinal dorsal horn of SP were significantly lower after inject capsaicin 5 min(P＜0.01),each group both have the downward trend after inject capsaicin 180 min. Compared with the group A and group C,the group B rat spinal dorsal horn in the SP-L1 is still at least(P＜0.05).Conclusion:Epidural application of capsaicin rats experienced the period of sensitization and desensitization.In sensitized rats decreased pain threshold while Substance P increased content, desensitization in rats increased pain threshold while Substance P content of a corresponding reduction.Substance P is recognized as the primary neurotransmitter neurons which can stimulate higher levels of pain transmission neurons upward,pain in the spinal cord in the transmission of information plays an important role. Capsaicin receptor from its role in nerve cells release of substance P is not yet fully aware of the specific machine,Purkiss,such as in vitro rat dorsal root ganglion cells were found that capsaicin may cause the release of Substance P through two mechanisms:A dependent on extracellular calcium and synaptic 25 Kpa of uncoupling protein(SNAP-25),the other is in the absence of extracellular calcium circumstances without SNAP-25,capsaicin can stimulate ganglion cells release of Substance P successfully,and ketamine can inhibit the application of capsaicin after sensitization caused by the release of a large number of substance P,the results show that the NMDA receptor channel high calcium ion permeability that can be activated intracellular calcium increased significantly,and the synthesis of NO can cause an increase in a series of cascading reaction amplification.Primary afferent hub on the presynaptic process NMDA receptor activation can be further promote calcitonin gene-related peptide(CGRP),the release of substance P and EAA which can induce the spinal dorsal horn neurons sensitive.Ketamine is commonly used glutamate NMDA receptor blockers which can block NMDA receptor optionally and central sensitization,inhibiting the release of substance P too. Tramadol is a kind of opioid central role of the potent analgesic drugs[4]which paly an important role and position in the spinal cord,brain and the spinal pain related receptor,it may be sympathetic activity through a non-opioid analgesic efficacy. Experiments found that tramadol can be slightly inhibited the release of substance P,but its mechanism is not clear which also to be further studied.We found that through application of capsaicin in the behavioral response,Application of low-dose epidural ketamine and tramadol both have the role of preemptive analgesia, which induced by capsaicin,also respiratory paralysis and nerve irritation pain can be eliminated,but only partially eliminate pain caused by capsaicin hypersensitive.Under normal circumstances, hypersensitive pain is that not lead to pain stimulus if can cause pain.Pain hypersensitivity can be induced by wooden or brush in some parts of the body or lightly brush lightly touch-induced dynamic,Pain hypersensitivity is often occurre when the role of ketamine and tramadol disappeared,when epidural to additional drugs,such pain hypersensitivity phenomenon may disappear,this phenomenon pain hypersensitivity mechanism to be further studied. Application of low-dose epidural ketamine and tramadol both have the role of preemptive analgesia,which induced by capsaicin,also respiratory paralysis and nerve irritation pain can be eliminated. Ketamine is more effective than tramadol to prevent the large number of SP to release,and the epidural effect of preemptive analgesia better. 属性不符...