方先海：Propofol local injection relieve neuropathic pain through suppressing NMDA-2B receptors of sciatic nerves in chronic constriction injury rats
发布日期：2012-08-30 16:38 文章来源：丁香园
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关键词： NMDA receptor
propofol
NR2B subunits
neuropathic pain
sciatic nerve
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Backgroud: Neuropathic pain is a complex, costly condition resulting from a primary lesion or dysfunction in any part of the nervous system, from the peripheral receptor to the brain. The exact mechanisms underlying neuropathic pain are still unclear, involving changes in afferent and central spinal sensory relays, leading to neuronal hyperexcitability[1-4]. Peripheral neuropathic pain arises as a result of various types of nerve damage, e.g., diabetic neuropathy, HIV neuropathy, post-herpetic neuralgia, drug-induced neuropathy and traumatic nerve injury. Peripheral nerve injury often results in neuropathic pain, characterised by hyperalgesia (increased pain elicited by noxious stimuli), allodynia (pain from normally innocuous stimuli) and spontaneous pain, which are difficult to treat [5]. The exact mechanism of neuropathic pain and the protective effect to peripheral nerves of propofol is still unknown. NMDA receptors may play an important role in neuropathic pain occurrence. Propofol as a widely used anesthetic possesses the antagonism effect of peripheral NMDA receptors.
Methods:This randomized double-blind placebo controlled trial was designed to evaluate the effectiveness and the mechanisms of local injection of propofol to neuropathic pain rats. The chronic constriction injury rats were differently injected propofol, lidocaine or saline by the side of sciatic nerve to investigate the efficacy and the mechanism of local injection of propofol.
Results:After the treatment of propofol the PWMT(paw withdrawl mechanical threshold) and PWTL(paw withdrawl thermal latency) of the CCI(chronic constriction injury to sciatic nerve) rats in propofol group are higher than the control group(P<0.05).
Compelling evidence has indicated that there are NMDA receptors at the sciatic nerves of mammals. Especially, the NMDARs activity has been established to exert a critical role in long-lasting modification of glutamate receptors-mediated synaptic strength. The trial aimed to evaluate whether local injection propofol react through NMDARs on sciatic nerves for alleviating neuropathic pain. Immunohistochemistry analysis showed that expression of NMDA-2B receptor on sciatic nerve was obviously suppressed in propofol group than other group (P<0.05)(Fig.1). But there are no significant difference between lidocaine-injected and saline-injected rats. We also find the expression of NR2B receptor in the control group was higher than the normal group which may be related to neuropathic pain.
The scores of sciatic nerves observed through electronic microscopy in each group have no statistic difference (P>0.05). Such findings support the use of the peripheral administration of propofol in treating neuropathic pain. Furthermore, we analyzed the abundance of NMDA-2B receptor in sciatic nerves after the treatment. The obtained results clarified the effect and mechanism of local injection of propofol beside sciatic nerve in neuropathic pain rats and these effects were mediated in part by peripheral NMDA-2B receptors localized at the side of sciatic nerve.
Conclusion:The obtained results clarified the effect and mechanism of local injection of propofol beside sciatic nerve in neuropathic pain rats and these effects were mediated in part by peripheral NMDA-2B receptors localized in the sciatic nerves.
Propofol local injection by the side of sciatic nerve can be of great value in the design of specific therapies and of great benefit to the design of clinical trials. It may also aid in advancing our understanding of the mechanisms involved in the pathophysiology of neuropathic pain, which may lead to novel treatments for this very severe condition.
Keywords:NMDA receptor; propofol; NR2B subunits; neuropathic pain; sciatic nerve
References
1 Kohama I, Ishikawa K, Kocsis JD. Synaptic reorganization in the substantia gelatinosa after peripheral nerve neuroma formation: aberrant innervation of lamina II neurons by Abeta afferents. J Neurosci. 2000;20:1538-49.
2 Laird JM, Bennett GJ. An electrophysiological study of dorsal horn neurons in the spinal cord of rats with an experimental peripheral neuropathy. J Neurophysiol. 1993;69:2072-85.
3 Takaishi K, Eisele JH, Jr., Carstens E. Behavioral and electrophysiological assessment of hyperalgesia and changes in dorsal horn responses following partial sciatic nerve ligation in rats. Pain. 1996;66:297-306.
4 Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature. 1983;306:686-8.
5 Arner S, Meyerson BA. Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain. 1988;33:11-23.
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