Articles: hyperalgesia.
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Randomized Controlled Trial
Ondansetron, a 5HT3-antagonist, does not alter dynamic mechanical allodynia or spontaneous ongoing pain in peripheral neuropathy.
The aim of this study was to examine whether the intensity of dynamic mechanical allodynia and spontaneous ongoing pain in patients with neuropathic pain associated with peripheral neuropathy was influenced by an intravenous infusion of the 5HT3-antagonist, ondansetron. ⋯ No influence from 8 mg of ondansetron could be shown on the intensity of brush-evoked or spontaneous ongoing pain in patients with peripheral neuropathy, indicating the lack of involvement of 5HT3-receptors in an earlier proposed spinobulbospinal loop with descending facilitation acting on spinal mechanisms related to dynamic mechanical allodynia.
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Eighteen patients with peripheral neuropathic pain (PNeP) and seven patients with central post-stroke pain (CPSP) all suffering from dynamic mechanical allodynia (DMA) in a limb were studied. From recent research it is reasonable to suggest that A-beta fibres constitute the peripheral substrate for DMA in patients with PNeP. The pathophysiological basis for DMA in patients with CPSP is unknown. ⋯ The rest of the patients lost DMA without transition to DMD. The transition or loss of DMA without transition occurred early and concurrently in time during the block and was paralleled by a continuous impairment of mainly A-beta fibre function. We therefore suggest DMA to be the hyperbole of DMD, the difference being the number of mechanoreceptive fibres having access to the nociceptive system.
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Anesthesia and analgesia · May 2011
Central and local administration of Gingko biloba extract EGb 761® inhibits thermal hyperalgesia and inflammation in the rat carrageenan model.
Oral administration of the standardized Ginkgo biloba extract EGb 761® has been shown to inhibit thermal hyperalgesia in rodent models of inflammatory and postsurgical pain, but the mechanism underlying these effects is not known. We sought to determine the site of action of EGb 761 by investigating the antihyperalgesic and antiinflammatory properties of EGb 761 after local and central drug administration in the rat carrageenan model of inflammation. ⋯ These studies show that EGb 761 acts both at the site of inflammation and centrally at the spinal cord level to inhibit inflammation and thermal hyperalgesia, and may be useful in the treatment of inflammatory pain.
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Intense noxious stimuli impair GABAergic inhibition in spinal dorsal horn, which has been proposed as a critical contributor to pathological pain. However, how the reduced inhibition exacerbates the transfer of nociceptive information at excitatory glutamatergic synapses is still poorly understood. The present study demonstrated that one of the striking consequences of GABAergic disinhibition was to enhance the function of N-methyl-D-aspartate subtype glutamate receptors (NMDARs), a well-characterized player in central sensitization. ⋯ When PKA inhibitor H-89 was intrathecally applied, it totally eliminated bicuculline-induced NMDARs phosphorylation, synaptic redistribution as well as pain sensitization. Importantly, the reduced inhibition also operated to enhance NMDARs functions after peripheral inflammation, because spinal injection of diazepam to rescue the inhibition in inflamed mice greatly depressed PKA phosphorylation of NR1-S897, reduced the synaptic concentration of NR1/NR2B and meanwhile, alleviated the inflammatory pain. These data suggested that removal of GABAergic inhibition allowed for PKA-mediated NMDARs phosphorylation and synaptic accumulation, thus exaggerating NMDARs-dependent nociceptive transmission and behavioral sensitization.
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Pharmacol. Biochem. Behav. · May 2011
Formalin-induced long-term secondary allodynia and hyperalgesia are maintained by descending facilitation.
This work analyzes the role of cholecystokinin (CCK) receptors, dynorphin A₁₋₁₇ and descending facilitation originated in the rostral ventromedial medulla (RVM) on secondary allodynia and hyperalgesia in formalin-injected rats. Formalin injection (50 μL, 1%, s.c.) produced acute nociception (lasting 1 h) and long-term secondary allodynia and hyperalgesia in ipsilateral and contralateral hind paws (lasting 1-12 days). Once established, intra-RVM administration of lidocaine at day 6, but not at 2, reversed secondary allodynia and hyperalgesia in rats. ⋯ Moreover, intrathecal administration of dynorphin antiserum reversed, but was unable to prevent, secondary allodynia and hyperalgesia in both hind paws. These results suggest that formalin-induced secondary allodynia and hyperalgesia are maintained by activation of descending facilitatory mechanisms which are dependent on CCK₂ receptors located in the RVM and spinal cord. In addition, data suggest that spinal dynorphin A₁₋₁₇ and CCK play an important role in formalin-induced secondary allodynia and hyperalgesia.