Articles: hyperalgesia.
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The vanilloid receptor 1 (VR1) is expressed by the type II A-delta and C-fiber neurons, functioning as a molecular integrator for nociception. VR1 can be selectively ablated by resiniferatoxin (RTX), an ultra-potent excitotoxic agonist, when injected into sensory ganglia. ⋯ VR1-positive neurons are essential for the development of mechanical allodynia. In rats already exhibiting neuropathic pain, the VR1-positive neurons mediate the most sensitive part of mechanical allodynia. RTX injection in sensory ganglia may represent a novel treatment for neuropathic pain.
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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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To investigate allodynia in patients with different primary headaches. ⋯ Allodynia is not specific to migraine but is frequent in all headache patients: acute allodynia was reported in half those interviewed and in over a third of patients in each headache category; interictal allodynia was reported by nearly 25%.
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Little is known regarding how cognitive strategies help to modulate neural responses of the human brain in ongoing pain syndromes to alleviate pain. Under pathological pain conditions, any self-elicited contact with usually non-painful stimuli may become painful. We examined whether the human brain is capable of dissociating self-controlled from externally administered thermal hyperalgesia in the experimental capsaicin model. ⋯ Some areas were able to dissociate between self- and externally administered stimuli in thermal hyperalgesia, which might be related to differences in perceived controllability. Thus, neural mechanisms maintain the ability to dissociate external from self-generated states of injury in thermal hyperalgesia. This may help to understand how cognitive strategies potentially alleviate chronic pain syndromes.