Articles: hyperalgesia.
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Changes in the signaling of wide dynamic range neurons and the expression of glutamate transporters in the lumbar spinal dorsal horn of rats with Taxol-induced hyperalgesia are detailed in this report. Deep spinal lamina neurons have significantly increased spontaneous activity and after-discharges to noxious mechanical stimuli, increased responses to both skin heating and cooling, and increased after-discharges and abnormal windup to transcutaneous electrical stimuli. ⋯ These results suggest a state of increased excitability develops in spinal pain-signaling neurons as a consequence of decreased glutamate clearance. These changes in dorsal horn neurobiology likely in turn contribute to the hyper-responsiveness to sensory stimuli seen in animals treated with Taxol and may play a role in the pain seen in cancer patients receiving Taxol.
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Numerous studies have implicated the cAMP-protein kinase A (PKA) pathway in producing hyperexcitability of dorsal root ganglia (DRG) sensory neurons under conditions associated with pain. Evidence is presented for roles of both the cAMP-PKA and cGMP-protein kinase G (PKG) pathways in maintaining neuronal hyperexcitability and behavioral hyperalgesia in a neuropathic pain model: chronic compression of the DRG (CCD treatment). Lumbar DRGs were compressed by a steel rod inserted into the intervertebral foramen. ⋯ Unexpectedly, application of these agonists and antagonists to ganglia of naïve, uninjured animals had little effect on electrophysiological properties of DRG neurons and no effect on foot withdrawal, suggesting that sensitizing actions of these pathways in the DRG are enabled by prior injury or stress. The only effect observed in uncompressed ganglia was modest depolarization of DRG neurons by PKA and PKG agonists. CCD treatment also depolarized DRG neurons, but CCD-induced depolarization was not affected by agonists or antagonists of these pathways.
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We have compiled a comprehensive QST protocol as part of the German Research Network on Neuropathic Pain (DFNS) using well established tests for nearly all aspects of somatosensation. This protocol encompasses thermal as well as mechanical testing procedures. Our rationale was to test for patterns of sensory loss (small and large nerve fiber functions) or gain (hyperalgesia, allodynia, hyperpathia), and to assess both cutaneous and deep pain sensitivity. ⋯ There was no significant right-to-left difference for any of the QST parameters; left-to-right correlation coefficients ranged between 0.78 and 0.97, thus explaining between 61% and 94% of the variance. This study has shown that a complete somatosensory profile of one affected area and one unaffected control area, which will be necessary to characterize patients with a variety of diseases, can be obtained within 1 h. Case examples of selected patients illustrate the value of z-transformed QST data for an easy survey of individual symptom profiles.
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Randomized Controlled Trial Comparative Study
Topically administered ketamine reduces capsaicin-evoked mechanical hyperalgesia.
The n-methyl-d-aspartate receptor antagonists such as ketamine relieve chronic pain but their oral and parenteral use is limited by the adverse effects. Experimental studies indicate that the peripheral n-methyl-d-aspartate receptors are involved in nociception. Recent clinical findings suggest that ketamine gel alleviates neuropathic pain, but no placebo-controlled randomized studies are available on the neurosensory effects of ketamine gel in experimental neurogenic pain. ⋯ A significant reduction of mechanical hyperalgesia was produced by topically and pre-emptively applied ketamine in healthy patients. We propose that the mechanism of action would be the reduction of central sensitization caused by the absorption of ketamine in circulation.
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Randomized Controlled Trial
A PET activation study of brush-evoked allodynia in patients with nerve injury pain.
Acute experimental brush-evoked allodynia induces a cortical activation pattern that differs from that typically seen during experimental nociceptive pain. In this study, we used positron emission tomography to measure changes in regional cerebral blood flow (rCBF) in patients with clinical allodynia. Nine patients with peripheral nerve injury were scanned during rest, brush-evoked allodynia, and brushing of normal contralateral skin. ⋯ A direct post hoc comparison of brush -and allodynia-induced rCBF changes showed that allodynia was associated with significantly stronger activations in orbitofrontal cortex and ipsilateral insula whereas non-painful brushing more strongly activated SI and BA 5/7. These findings indicate that activity in the cortical network involved in the sensory-discriminative processing of nociceptive pain is downregulated in neuropathic pain. Instead, there is an upregulation of activity in the orbitofrontal and insular cortices, which is probably due to the stronger emotional load of neuropathic pain and higher computational demands of processing a mixed sensation of brush and pain.