Articles: hyperalgesia.
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Neuroscience letters · Jan 2003
Comparative StudyAttenuation of mechanical hyperalgesia following spinal cord injury by administration of antibodies to nerve growth factor in the rat.
Spinal cord injury (SCI) often leads to central pain syndrome including hyperalgesia to mechanical stimulation. Since there is evidence that nerve growth factor (NGF) contributes to pain-related behaviors, we wished to determine if anti-NGF might inhibit abnormal somatosensory behaviors that develop following SCI in rats. SCI was performed in male Sprague-Dawley rats by T13 spinal hemisection. ⋯ Mechanical responsiveness of wide dynamic range (WDR) neurons on both sides of spinal cord also increased. The anti-NGF treated group demonstrated significant suppression of both mechanical hyperalgesia and increased WDR neuronal responsiveness. These results indicate that anti-NGF prevents the development of abnormal somatosensory behavior and suggest a potential pre-emptive analgesic treatment for central pain.
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Spinal cord dorsal horn N-methyl-D-aspartate (NMDA) receptors have been implicated in central sensitization, enhanced responsiveness to peripheral stimuli following peripheral injury. Since hyperalgesia is a behavioral consequence of central sensitization, it should be attenuated at the level of the dorsal horn with NMDA receptor antagonists. However, responsiveness to thermal and mechanical hyperalgesia may be distinct, and have thus far not been directly compared in chronic inflammatory pain models. ⋯ The NMDA receptor antagonists dose-dependently ameliorated mechanical hyperalgesia, but had marginal effects on thermal hyperalgesia. In ranges near antihyperalgesic doses, significant disruption of motor coordination was observed for both antagonists. These results suggest that, depending on the stimulus, NMDA receptors may have variable significance for central sensitization-mediated hyperalgesia, and that NMDA receptor antagonists may have therapeutic potential for some, but not all components in the clinical manifestation of inflammatory pain.
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Clinical Trial
Multi-modal induction and assessment of allodynia and hyperalgesia in the human oesophagus.
Experimental pain models based on single stimuli have to some degree limited visceral pain studies in humans. Hence, the aim of this study was to investigate the effect of multi-modal visceral pain stimuli of the oesophagus in healthy subjects before and after induction of visceral hyperalgesia. We used a multi-modal psychophysical assessment regime and a neurophysiological method (nociceptive reflex) for the characterisation of the experimentally induced hyperalgesia. ⋯ Visceral hyperalgesia/allodynia can be induced experimentally and assessed quantitatively by the newly introduced multi-modal psychophysical assessment approach. The significant changes of the experimentally evoked referred pain patterns and of the nociceptive reflex evoked from a distant somatic structure indicate that even short-lasting visceral hyperalgesia can generate generalised sensitisation.
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To date, the exact role of inducible nitric oxide synthase (iNOS) in inflammatory pain remains controversial. In the present study, we combined a pharmacological strategy (using a selective iNOS inhibitor) with a genomic strategy (using mice lacking the iNOS gene) to address the function of iNOS in the central mechanism of carrageenan-induced persistent inflammatory pain. In the wild type mice, intrathecal administration of L-N(6)-(1-iminoethyl)-lysine, a selective iNOS inhibitor, significantly inhibited thermal hyperalgesia in the late phase but not in the early phase of carrageenan inflammation. ⋯ We also found that expression of neuronal NOS but not endothelial NOS in the lumbar enlargement segments was significantly increased in iNOS knockout mice compared with wild type mice at 24 h after carrageenan injection. Our results indicate that neuronal NOS might compensate for the function of iNOS in the late phase of carrageenan-induced inflammatory pain in iNOS knockout mice. This suggests that iNOS may be sufficient, but not essential, for the late phase of the carrageenan-induced thermal hyperalgesia.
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One of the most prominent features of secondary hyperalgesia is touch-evoked pain, i.e., pain evoked by dynamic tactile stimuli applied to areas adjacent or remote from the originating injury. It is generally accepted that the neurobiological mechanism of this sensory alteration involves the central nervous system (CNS) so that incoming impulses in low-threshold mechanoreceptors from the area of secondary hyperalgesia can evoke painful sensations instead of touch. ⋯ Here we review the evidence gathered in support of this model in the intervening years with special reference to experimental studies of antidromic activity (Dorsal Root Reflexes--DRRs) in nociceptive afferents and on the acquisition of low-threshold inputs by nociceptor-specific neurons in the spinal dorsal horn. We also discuss and identify potential molecular mechanisms that may underlie the presynaptic interaction model and therefore that could be responsible for the development of secondary hyperalgesia.