Articles: hyperalgesia.
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There is general agreement that activation of the N-methyl-D-aspartate receptor is involved in thermal hyperalgesia. However, there is less agreement on the specific intracellular events subsequent to receptor activation and the involvement of other excitatory amino acid receptors in thermal hyperalgesia. In the present study, we found that the intrathecal administration of N-methyl-D-aspartate produced a dose- (1 fmol-1 pmol) and time-dependent thermal hyperalgesia. ⋯ Activation of AMPA, metabotropic or co-activation of AMPA and metabotropic glutamate receptors, at the doses tested, did not produce an acute thermal hyperalgesia. The thermal hyperalgesia produced by N-methyl-D-aspartate is mediated by activation of nitric oxide synthase and protein kinase C, but not by phospholipase C, phospholipase A2, cyclo-oxygenase or lipoxygenase. Collectively, the results are consistent with a role for spinal N-methyl-D-aspartate receptors, nitric oxide and protein kinase C in thermal hyperalgesia.
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Clinical Trial
Mechanisms of allodynia: interactions between sensitive mechanoreceptors and nociceptors.
We examined whether stimulation of sensitive mechanoreceptors from an area of allodynia evokes nociceptor activity expressed as axon reflexes. Experiments were conducted on human volunteers. Cutaneous blood flow was measured with a laser Doppler flowmeter. ⋯ The same stimulation in areas of allodynia evoked pain as well as axon reflexes. Cooling the area of primary hyperalgesia or blocking the A fibres in the nerve that innervated the allodynia area abolished the allodynia and the axon reflex. These results demonstrate central interactions between sensitive mechanoreceptors and nociceptors concomitant with the development of allodynia.
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Neuroscience letters · Jan 1996
Comparative StudyChanges in activity of spinal cells with muscular input in rats with referred muscular hyperalgesia from ureteral calculosis.
In rats with hyperalgesia of the obliquus externus muscle (OE) from artificial calculosis of the ipsilateral upper ureter, changes in cell activity were studied in the ipsilateral spinal cord (T11-T12) versus control animals. In cases of hyperalgesia of high degree, in the dorsal horn (0-900 microns) the following were found: significantly higher percentages of cells driven by OE stimulation (P < 0.03) and of spontaneously active cells with OE input (P < 0.02); significantly higher frequency of background discharge of cells with OE input (P < 0.002); among cells driven by OE stimulation, significantly higher percentages of neurons with exclusively deep input (P < 0.0006) and of neurons with low mechanical threshold of activation (P < 0.03). In the intermediate region of the cord (900-1600 microns), a significantly higher percentage was found of spontaneously active cells with OE input (P < 0.009) while in the ventral horn (1600-2300 microns) no changes were detected. The results indicate that referred muscle hyperalgesia of high degree is accompanied by a state of central sensitization probably triggered by the abnormal afferent input from the visceral focus.
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Comparative Study
An isobolographic analysis of the effects of N-methyl-D-aspartate and NK1 tachykinin receptor antagonists on inflammatory hyperalgesia in the rat.
1. The interaction between N-methyl-D-aspartate (NMDA) and NK1 tachykinin receptors was analyzed isobolographically in rats with inflammatory hyperalgesia induced by intraplantar injection of complete Freund's adjuvant-saline emulsion (CFA, 100 micrograms Mycobacterium tuberculosis). 2. Thermal hyperalgesia of the inflamed paw, determined by paw withdrawal response to a heat stimulus, was dose-dependently attenuated by intrathecal administration of an NMDA receptor antagonist, dextrorphan (2.5-40 micrograms, ED50 = 7.2 micrograms), and two NK1 tachykinin receptor antagonists, WIN 51,708 (0.01-200 micrograms, ED50 = 10.4 micrograms) or CP-96,345 (5-200 micrograms, ED50 = 82.1 micrograms). ⋯ Isobolographic analysis revealed that the ED50s obtained from the three combination ratios were not significantly different from those that were expected from a simple additive effect. 4. Thus, an additive interaction was demonstrated between NMDA and NK1 tachykinin receptor systems at the spinal level. These results suggest that both NMDA and NK1 tachykinin receptors are activated in response to peripheral inflammation, but that they may contribute independently to development of hyperalgesia.
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Review
Interactions of sympathetic and primary afferent neurons following nerve injury and tissue trauma.
Sympathetic post-ganglionic neurons may be involved in the generation of pain, hyperalgesia and inflammation under pathophysiological conditions. Two categories of influence of the sympathetic neuron on afferent neurons can be distinguished and this distinction seems to be related to whether the coupling between afferent and sympathetic neuron develops after nerve lesion or after tissue trauma with inflammation (Fig. 15): A. Peripheral nerve lesion generates plastic changes of the afferent and sympathetic postganglionic neurons, depending on the type of nerve lesion (e.g. complete, partial). ⋯ Sympathetically mediated (neurogenic) inflammation and neurogenic inflammation mediated by afferents may interact reciprocally and enhance the inflammatory process as well as the sensitization of nociceptive afferents. Norepinephrine may also lead to sensitization of nociceptive afferents under inflammatory conditions. This sensitization is presumably mediated by alpha 2-adrenoceptors in the sympathetic varicosities and by a prostaglandin (probably PGI2) which is synthesized and released by or in association with the sympathetic varicosities.