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SP And NK-1 Receptor Promote Activation Of Astrocytes In The Dorsal Horn Of Spinal Cord During Nociceptive Inputs Of Rats

Posted on:2006-10-28Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y MaFull Text:PDF
GTID:2144360152981670Subject:Pathology and pathophysiology
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Pain is a very common symptom in clinical casese and it makes people suffer from great distress. Recent studies suggest that glia within the dorsal horn of spinal cord play important role in the development and maintenance of pathological pain. For example, a variety of noxious stimulations, such as subcutaneous injection of formalin, zymosan , snake venom, can activate astrocytes of the dorsal horn of the spinal cord and upregulate the expression of glia fibrillary acidic protein (GFAP). Intrathecal injection of inhibitors of glia (such as CNI-1493,Propentofylline) can block thermal and mechanical hyperalgesia induced by many kinds of noxious stimulations. On the condition of pathological pain state, activated glia release a variety of neuroactive substances, including leukotriene, prostaglandins, excitatory amino acid, cytokines (such as IL-1,IL-6,TNF ) and so on. These neuroactive subs-tances can act on pain transmission neurons in the dorsal horn of the spinal cord and make them sensitive to stimuli. On the other hand, they can promote the release of substance P and excitatory amino acid from primary afferent terminals in the spinal cord. These results show that the activation of spinal glia is very important for pathological pain and hyperalgesia. However, the mechanism of the activation of glia in spinal cord induced by nociceptive inputs remains to be clarified. SP which acted on NK-1 receptor, was an important neurotransmitter in transmission of nociceptive information in the spinal cord. Studies show that there are NK-1 receptors on astrocytes. SP can promote the synthesis of DNA in astrocytoma cells and induce astrocytoma cells to secrete IL-1 and TNF-α. IL-1 and TNF-αare very important for pathological pain. Based on these investigations, it is conceivable that activation of astrocytes in the dorsal horn of the spinal cord in pain and nociception are related to release of SP and activation of NK-1 receptor. Thereby, to explore the role of SP and NK-1 receptor in the activation of astrocytes in dorsal horn of spinal cord induced by nociceptive inputs, the present study was undertaken to observe the influence of NK-1 receptor antagonist L-732,138 on GFAP expression in dorsal horn of spinal cord during the course of inflammatory pain and hyperalgesia in rats induced by subcutaneous injection of bee venom, and the changes of GFAP expression in the rat spinal cord during nociception induced by NK-1 receptor agonist [Sar9, Met (O2)11]-substance P (Sar-SP). 1. The effect of NK-1 receptor antagonist L-732,138 onthe GFAP expression in the dorsal horn of the spinal cord during bee venom-induced inflammatory pain and hyperalgesia of rats Seventy-seven male Sprague-Dawley rats (270-280g in weight) were divided into four groups randomly: control group, bee venom group, bee venom + DMSO group, bee venom + L-732,138 group. Based on the dosage of L-732,138 used, bee venom + L-732,138 group was further divided into 2nmol(2×10-4mol/L),20nmol(2×10-3mol/L) ,200nmol(2×10-2mol/L) subgroups. NS(50μl) was injected subcutaneously in rats in Control group. Bee venom solution(4g/L) was injected subcutaneouly into hindpaw to induce inflammatory pain and hyperalgesia in rats in bee venom + DMSO group, bee venom + L-732,138 group. The control rats were injected with NS in the same volume to BV solution. Ten microliter DMSO(80%) or L-732,138 was injected intrathecally before bee venom injection in rats in bee venom + DMSO group and bee venom + L-732,138 group. All rats in other groups were sacrificed at 1h and 24h after NS or bee venom injection, following counting number of flinches at 1h and measuring tail-flick latency at 24h, the changes of expression of GFAP in the dorsal horn of spinal cord were observed using immunohistochemistry method. The results were as follows: ①Rats showed flinches after bee venom injection. Intrathecal injection of DMSO had no effect on the number of flinches(P>0.05 vs BV group). However, intrathecal injection of L-732,138 can significantly decrease theflinches of rats(P<0.05 vs B...
Keywords/Search Tags:Substance P, GFAP, L-732,138, Sar-SP, inflammatory pain and hyperalgesia, nociception, spinal cord, rat
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