Articles: hyperalgesia.
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Anesthesia and analgesia · Mar 2008
The effects of intrathecal cyclooxygenase-1, cyclooxygenase-2, or nonselective inhibitors on pain behavior and spinal Fos-like immunoreactivity.
Prostaglandins are synthesized by cyclooxygenase (COX) and are thought to play an important role in nociceptive transmission in the spinal cord. Fos expression is an indicator of spinal neuron activation. We examined the role of intrathecal selective and nonspecific COX inhibitors on spinal C-Fos expression. ⋯ A dual inhibitor of COX-1 and COX-2 suppressed both responses of formalin-evoked behaviors and FLI expression of whole laminae in the lumbar spinal cord. FLI expression of laminae I-II alone may not be a good indicator of the ability to produce anti-hypersensitivity; however, the FLI of laminae V-VI correlates with phase 2 responses.
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Neuroscience letters · Feb 2008
A transient receptor potential vanilloid 4 contributes to mechanical allodynia following chronic compression of dorsal root ganglion in rats.
The aim of the present study was to investigate the role of transient receptor potential vanilloid 4 (TRPV4) in mediating mechanical allodynia in rodent models of chronic compression of the dorsal root ganglion (CCD). First, the levels of TRPV4 mRNA and protein expression in the dorsal root ganglion (DRG) were assessed using real-time RT-PCR and Western blotting analysis respectively at 7, 14, and 28 days post-CCD. Then, the effects of spinal administration of TRPV4 antisense oligodeoxynucleotide (ODN) and mismatch ODN on CCD-induced mechanical allodynia were evaluated. ⋯ The percentage of DRG neurons responsive to hypotonic solution and 4alpha-PDD and the fluorescence ratio of calcium response were also enhanced significantly in both the CCD group and the mismatch ODN group. These increased responses were significantly inhibited by TRPV4 antisense ODN. In conclusion, TRPV4 plays a crucial role in CCD-induced mechanical allodynia.
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J. Neurosci. Methods · Feb 2008
Inflammatory pain in the rabbit: a new, efficient method for measuring mechanical hyperalgesia in the hind paw.
The discovery of novel analgesic compounds that target some receptors can be challenging due to species differences in ligand pharmacology. If a putative analgesic compound has markedly lower affinity for rodent versus other mammalian orthologs of a receptor, the evaluation of antinociceptive efficacy in non-rodent species becomes necessary. Here, we describe a new, efficient method for measuring inflammation-associated nociception in conscious rabbits. ⋯ An established hyperalgesia was dose dependently reversed by morphine sulfate (ED50=0.096 mg/kg, s.c.) or the bradykinin B1 receptor peptide antagonist [des-Arg10, Leu9]-kallidin (ED50=0.45 mg/kg, s.c.). Rabbits treated with the novel B(1) receptor small molecule antagonist compound A also showed dose-dependent reversal of hyperalgesia (ED50=20.19 mg/kg, s.c.) and analysis of plasma samples taken from these rabbits showed that, unlike other rabbit pain models, the current method permits the evaluation of pharmacokinetic-pharmacodynamic (PK-PD) relationships (compound A plasma EC50=402.6 nM). We conclude that the Electrovonfrey method can be used in rabbits with inflammatory pain to generate reliable dose- and plasma concentration-effect curves for different classes of analgesics.
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Guanethidine displaces noradrenaline from sympathetic varicosities, and blocks sympathetic noradrenergic neurotransmission by inhibiting the release of noradrenaline from depleted neural stores. The aim of this study was to determine whether depletion of noradrenaline with guanethidine would oppose thermal hyperalgesia and/or electrically-evoked pain in mildly-burnt skin. Guanethidine was transferred by iontophoresis into a small patch of skin on the forearm of 35 healthy human subjects. ⋯ These findings indicate that ongoing sympathetic neural discharge does not normally influence thermal hyperalgesia in inflamed skin, because depleting noradrenergic stores had no effect. However, electrically-evoked release of noradrenaline may increase nociceptive sensations. Further clarification of this human pain model could provide insights into the mechanism of adrenergic hyperalgesia in certain neuropathic pain syndromes.
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To develop and validate a questionnaire for assessing cutaneous allodynia (CA), and to estimate the prevalence and severity of CA in the migraine population. ⋯ The Allodynia Symptom Checklist measures overall allodynia and subtypes. CA affects 63% of migraineurs in the population and is associated with frequency, severity, disability, and associated symptoms of migraine. CA maps onto migraine biology.