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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Opioids can induce analgesia and also hyperalgesia in humans and in animals. It has been shown that systemic administration of morphine induced a hyperalgesic response at an extremely low dose. However, the exact mechanism(s) underlying opioid-induced hyperalgesia has not yet been clarified. ⋯ KT 5720, a specific inhibitor of protein kinase A (PKA), did not show any effect on low-dose morphine-induced hyperalgesia. These results indicate a role for G(alphas), the PLC-PKC pathway, and L-type calcium channels in intrathecal morphine-induced hyperalgesia in rats. Activation of ordinary G(alphas) signaling through cAMP levels did not appear to play a major role in the induction of hyperalgesia by low-dose of morphine.
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The aim of the study was to investigate if an abnormal brain response to pain exists in patients with myofascial pain syndrome (MPS) when stimulated in a hypersensitive myofascial trigger point (MTP). Event-related functional magnetic resonance imaging was used to characterize the brain response to pain evoked from an MTP. Activation patterns from patients were compared with those evoked from an equivalent site in healthy controls with stimulus intensity matched and pain intensity matched stimuli. ⋯ At matched pain intensity, enhanced activity was found in the same somatosensory areas but not in limbic areas. Our results show that the hyperalgesic state observed in MPS patients was associated with abnormal hyperactivity in regions processing stimulus intensity and negative affect. We speculate that suppressed hippocampal activity might reflect stress-related changes in relation to chronic pain as an effective physical and emotional stressor.