Articles: hyperalgesia.
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The Journal of physiology · Nov 2010
Magnesium attenuates chronic hypersensitivity and spinal cord NMDA receptor phosphorylation in a rat model of diabetic neuropathic pain.
Neuropathic pain is a common diabetic complication affecting 8-16% of diabetic patients. It is characterized by aberrant symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. Magnesium (Mg) deficiency has been proposed as a factor in the pathogenesis of diabetes-related complications, including neuropathy. ⋯ Magnesium supplementation failed to reduce hyperglycaemia, polyphagia and hypermagnesiuria, or to restore intracellular Mg levels and body growth, but increased insulinaemia and reduced polydipsia. Moreover, it abolished thermal and tactile allodynia, delayed the development of mechanical hypersensitivity, and prevented the increase in spinal cord dorsal horn pNR1. Thus, neuropathic pain symptoms can be attenuated by targeting the Mg-mediated blockade of NMDA receptors, offering new therapeutic opportunities for the management of chronic neuropathic pain.
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Treatment with opioid medications has grown over the past decades, but has been surrounded by some ongoing controversy and debate to whether it is causing more harm than good for patients. To this end, the field of pain management has suffered from a lack of clarity about some basic definitions on concepts such as tolerance and hyperalgesia. Some characterize these issues as inevitable parts of opioid therapy while other schools of thought look at these issues as relatively rare occurrences. ⋯ Looking at the pattern of medication usage change over time, 34.5 percent experienced dose stabilization after the initial titration, 13.2 percent had early dose stabilization within one dose change, and an additional 14.7 percent actually had dose decreases after surgeries or other interventional procedures. Only 6.6 percent of the sample had to be discharged or weaned from controlled substances over time in the clinic. Thus, it appears that tolerance and hyperalgesia are not foregone conclusions when considering placing a patient on long-term opioid therapy.
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J. Neurosci. Methods · Oct 2010
A novel animal model of graded neuropathic pain: utility to investigate mechanisms of population heterogeneity.
The mechanisms underlying neuropathic pain are not well understood, resulting in unsatisfactory treatment outcomes for many patients. Animal models underpin much of the current understanding of pain mechanisms due to their perceived ability to mimic pain hypersensitivities; however, are limited by their binomial approach (pain vs. control), which does not reflect the clinical heterogeneity in nociceptive hypersensitivity. We modified the chronic constriction injury model by varying the number of sciatic nerve chromic gut sutures. ⋯ Astrocyte GFAP expression was positively associated with graded allodynia in the ipsilateral dorsal horn (P=0.18, r(2)>0.6) and ipsilateral DLF (P<0.05, r(2)>0.9). DLF glial activation may represent a contributor to contralateral pain. Our novel graded model has a dynamic range, allowing sensitive detection of interactions and subtle influences on neuropathic pain processing.
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Activation of glutamate receptors and glial cells in the spinal dorsal horn are two fundamental processes involved in the pathogenesis of various pain conditions, including neuropathic pain induced by injury to the peripheral or central nervous systems. Numerous studies have demonstrated that minocycline treatment attenuates allodynic and hyperalgesic behaviors induced by tissue inflammation or nerve injury. However, the synaptic mechanisms by which minocycline prevents hyperalgesia are not fully understood. ⋯ Minocycline ameliorated both the downregulation of glial GT expression and the activation of astrocytes induced by pSNL in the spinal dorsal horn. We further revealed that preventing deficient glial glutamate uptake at the synapse is crucial for preserving the normalized activation of NMDA receptors in the spinal sensory synapses in pSNL rats treated with minocycline. Our studies suggest that glial GTs may be a potential target for the development of analgesics.
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The aim of this study was to investigate the role of P2X3, P2X2/3 and P2X7 receptors in the development of TMJ hyperalgesia induced by carrageenan. We also investigated the expression of mRNA of P2X7 receptors in the trigeminal ganglia and the existence of functional P2X7 receptors in the rat's TMJ. The P2X1, P2X3 and P2X2/3 receptor antagonist TNP-ATP, but not the selective P2X7 receptor antagonist A-438079, significantly reduced carrageenan-induced TMJ inflammatory hyperalgesia. ⋯ However, functional P2X7 receptors are expressed in the TMJ region. The activation of these receptors by BzATP sensitizes the primary afferent nociceptors in the TMJ through the previous release of inflammatory mediators. The findings of this study point out P2X3 and P2X2/3 receptors, but not P2X7 receptors, as potential targets for the development of new analgesic drugs to control TMJ inflammatory pain.