Articles: hyperalgesia.
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Clin Physiol Funct Imaging · Mar 2004
Randomized Controlled Trial Clinical TrialDifferential effects of peripheral ketamine and lidocaine on skin flux and hyperalgesia induced by intradermal capsaicin in humans.
The capsaicin-induced flux in the primary and secondary hyperalgesic area after pretreating the capsaicin injection site with local ketamine, lidocaine or saline 10 min prior to injection was examined in this study. Twelve healthy volunteers participated in two randomized, double-blinded, placebo-controlled, cross-over experiments. In the first experiment, the skin on the volar forearm was pretreated with s.c. ketamine or saline, 10 min prior to capsaicin injection. ⋯ Only lidocaine reduced spontaneous pain, evoked pain and areas of hyperalgesia, whereas ketamine had no effect. Our results suggest that there is no simple and close relation between vascular and sensory reactions to pharmacological manipulation following intradermal capsaicin injection. We propose distinct mechanisms for local lidocaine and ketamine based on the differential effects of local lidocaine and ketamine on flux and pain.
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Randomized Controlled Trial Clinical Trial
The development and maintenance of human visceral pain hypersensitivity is dependent on the N-methyl-D-aspartate receptor.
Visceral hypersensitivity is a common feature of functional gastrointestinal disorders. One speculated mechanism is an activity-dependent increase in spinal cord neuronal excitability (central sensitization), which is dependent on activation of the N-methyl-D-aspartate (NMDA) receptor. Our aims were to determine whether the development and maintenance of human visceral hypersensitivity is NMDA receptor mediated. ⋯ The induction and maintenance of acid-induced esophageal hypersensitivity is prevented and reversed by ketamine. This finding strongly indicates that central sensitization is a mechanism of visceral hypersensitivity.
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Comparative Study
Comparison of hyperalgesia induced by capsaicin injection and controlled heat injury: effect on temporal summation.
The relationship between induction of central sensitization and facilitation of temporal summation to repetitive stimulation is still unclear. The aim of this study was to investigate temporal summation before and after the induction of secondary hyperalgesia by two different experimental methods: capsaicin injection and controlled heat injury. The effect of each injury model was assessed on a separate day with an interval of at least 5 days. ⋯ In contrast, for the mechanical impact and punctuate mechanical stimuli the degree of temporal summation was significantly facilitated in the secondary hyperalgesic areas compared with the baseline and the control arm in both models. In the primary hyperalgesic area, the degree of temporal summation was facilitated to mechanical impact and punctuate stimuli but only following the capsaicin injection. In conclusion, the temporal summation mechanism for mechanical stimuli was facilitated in the secondary hyperalgesic area.
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The aging process is associated with various morphological and biochemical changes in the nervous system that may affect the processing of noxious inputs. This study showed greater hyperalgesia and up-regulation of spinal dynorphin (DYN) expression in aging than in young adult rats during CFA-induced peripheral inflammation. These data indicate that nociception is regulated differently in aging individuals, a fact that should be considered when selecting treatment strategies for aging populations with persistent pain.
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Phosphorylation of IkappaB through IkappaB kinase (IKK) is the first step in nuclear factor kappaB (NF-kappaB) activation and upregulation of NF-kappaB-responsive genes. Hence, inhibition of IKK activity may be expected to prevent injury-, infection-, or stress-induced upregulation of various proinflammatory genes and may thereby reduce hyperalgesia and inflammation. In the present study, we tested this hypothesis using a specific and potent IKK inhibitor (S1627). ⋯ The drug had no effect on acute inflammatory nociception in the formalin test and did not affect responses to heat and tactile stimuli in naive animals. As hypothesized, S1627 prevented the zymosan-induced nuclear translocation of NF-kappaB in the spinal cord and the upregulation of NF-kappaB-responsive genes including cyclooxygenase-2, tumor necrosis factor-alpha, and IL-1beta. Our data indicate that IKK may prove an interesting novel drug target in the treatment of pathological pain and inflammation.