Effects of low-affinity NMDA receptor channel blockers in two rat models of chronic pain

Medvedev, Ivan O.; Malyshkin, A.; Belozertseva, Irina; Sukhotina, I. A.; Sevostianova, Natalia; Алиев, К Т; Zvartau, Edwin; Parsons, Chris G.; Danysz, Wojciech; Bespalov, Anton

doi:10.1016/j.neuropharm.2004.01.019

Cited by 35 publications

(29 citation statements)

References 29 publications

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“…Several authors have demonstrated evidence of the efficacy of NMDA receptor antagonists in chronic pain, e.g. neuropathy [11,12,13,14,15,16]. Moreover, NMDA receptor antagonists in combination with opioids have been shown to be more effective than opioids administered alone in different kinds of this pain [17,18,19,20].…”

Section: Discussionmentioning

confidence: 99%

Additive Effect of Combined Application of Magnesium and MK-801 on Analgesic Action of Morphine

Bujalska‐Zadrożny

Duda²

2014

Pharmacology

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As previously reported, magnesium ions (Mg²⁺) administered in relatively low doses markedly potentiated opioid analgesia in neuropathic pain, in which the effectiveness of opioids is limited. Considering that Mg²⁺ behaves like an N-methyl-D-aspartate receptor antagonist, the effect of this ion on the analgesic action of morphine was compared with that of MK-801. Acute pain was evoked by mechanical or thermal stimuli, whereas neuropathic hyperalgesia was induced by streptozotocin (STZ) administration. Magnesium sulphate (40 mg/kg i.p.) or MK-801 (0.05 mg/kg s.c.) administered alone did not modify the nociceptive threshold to acute stimuli or the streptozotocin hyperalgesia but significantly augmented the analgesic action of morphine (5 mg/kg i.p.). Furthermore, if these drugs (i.e. magnesium sulphate and MK-801) were applied concomitantly, a clear additive effect on the analgesic action of morphine occurred in both models of pain. Possible explanations of these observations are discussed.

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Section: Discussionmentioning

confidence: 99%

Additive Effect of Combined Application of Magnesium and MK-801 on Analgesic Action of Morphine

Bujalska‐Zadrożny

Duda²

2014

Pharmacology

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“…The majority of studies characterized the NMDA receptor antagonists as enhancing or having no effect on analgesia, whereas a minority demonstrated attenuation of acute morphine analgesia (88)(89)(90)(91)(92)(93). One challenge in this area is the absence of consistent results identifying which opioids exhibit NMDA receptor antagonist-enhanced antinociception.…”

Section: Nmda Receptor Contributions To Opioid Tolerancementioning

confidence: 99%

Opioid Tolerance Development: A Pharmacokinetic/Pharmacodynamic Perspective

Dumas

Pollack

2008

AAPS J

231

164

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Abstract. The opioids are commonly used to treat acute and severe pain. Long-term opioid administration eventually reaches a dose ceiling that is attributable to the rapid onset of analgesic tolerance coupled with the slow development of tolerance to the untoward side effects of respiratory depression, nausea and decreased gastrointestinal motility. The need for effective-long term analgesia remains. In order to develop new therapeutics and novel strategies for use of current analgesics, the processes that mediate tolerance must be understood. This review highlights potential pharmacokinetic (changes in metabolite production, metabolizing enzyme expression, and transporter function) and pharmacodynamic (receptor type, location and functionality; alterations in signaling pathways and crosstolerance) aspects of opioid tolerance development, and presents several pharmacodynamic modeling strategies that have been used to characterize time-dependent attenuation of opioid analgesia.

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“…Some papers showed the analgesic effects of NMDA receptor antagonists in rats with neuropathic pain (Carlton and Hargett 1995;Eisenberg et al 1995;Medvedev et al 2004). The hyperactivation of the NMDA receptors leads to excessive glutamate release, which causes neuronal dysfunctions and cell damage or death in acute neurodegenerative diseases such as stroke and ischemia.…”

Section: Early Administration Of Memantine Inhibits the Development Omentioning

confidence: 99%

“…Several behavioral studies have demonstrated that memantine attenuates allodynia and hyperalgesia postsciatic nerve injury and formalin injection (Carlton and Hargett 1995;Eisenberg et al 1995;Medvedev et al 2004;Wilson et al 2005). Memantine, noncompetitive NMDA receptor antagonist, is being used now to be a clinically promising drug for Alzheimer's disease in Europe and USA, because of its low neurotoxicity (Kato 2004).…”

Section: Introductionmentioning

confidence: 99%

Effect of Memantine on the Levels of Neuropeptides and Microglial Cells in the Brain Regions of Rats with Neuropathic Pain

et al. 2009

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Neuropathic pain induced by sciatic nerve injury not only causes peripheral dysfunctions but also affects the cortical and subcortical regions of the brain. It is still unknown whether neuropathic pain could relate to behavioral and neurochemical alterations in the central nervous system. This paper deals with the effect of peripheral neuropathic pain on mechanical allodynia, neuropeptide levels, neuropeptide-degrading enzyme activities, and microglial cells in the brain regions of rats by applying chronic constriction injury, a partial sciatic nerve injury. We examined the possible protection effect on the allodynia and changes in levels of neuropeptides and microglial activation in chronic constriction injury of the rat brain by memantine. On 4 days after chronic constriction injury, the induction of mechanical allodynia was suppressed by memantine treatment. Reductions in the substance P in the hypothalamus and somatostatin in the periaqueductal gray of chronic constriction injury rat brain were reversed by memantine. This suggests the role of these neuropeptides in pain information processing in the brain. Immunohistochemical experiments revealed that the expression of CD11b, a marker protein of microglia, was increased in the hypothalamus and periaqueductal gray in the chronic constriction injury rat brain as compared with the controls, and memantine treatment could suppress the activation of microglia, suggesting the involvement of microglia in pain mechanism. The present behavioral, biochemical, and immunohistochemical studies demonstrated that peripheral neuropathic pain affects the neuropeptide levels and microglial activation in the brain regions, and these events described above may play an important role in neuropathic pain pathogenesis.

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Effects of low-affinity NMDA receptor channel blockers in two rat models of chronic pain

Cited by 35 publications

References 29 publications

Additive Effect of Combined Application of Magnesium and MK-801 on Analgesic Action of Morphine

Additive Effect of Combined Application of Magnesium and MK-801 on Analgesic Action of Morphine

Opioid Tolerance Development: A Pharmacokinetic/Pharmacodynamic Perspective

Effect of Memantine on the Levels of Neuropeptides and Microglial Cells in the Brain Regions of Rats with Neuropathic Pain

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