Articles: hyperalgesia.
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Randomized Controlled Trial Clinical Trial
Mechanically induced axon reflex and hyperalgesia in human UV-B burn are reduced by systemic lidocaine.
The mechanisms for the induction of primary mechanical hyperalgesia are unclear. We analyzed the neurogenic axon reflex erythema (flare) following phasic mechanical stimulation in normal and in UV-B irradiated skin. In a cross-over double blind design (n = 10), low dose of systemic lidocaine suppressed mechanical hyperalgesia in sunburned skin and in the mechanically induced flare. ⋯ Systemic lidocaine suppressed the mechanically induced flare as well as the mechanical hyperalgesia in sunburned skin, while leaving the impact-induced ratings in normal skin unchanged. Systemic lidocaine reduced these effects of sensitization, but did not reduce ratings in normal skin. As mechanically insensitive ("sleeping") nociceptors have been shown to mediate the axon-reflex in human skin, sensitization of this class of nociceptors might contribute also to the UV-B-induced primary mechanical hyperalgesia.
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Pharmacol. Biochem. Behav. · Jun 2004
Randomized Controlled Trial Comparative Study Clinical TrialLack of effect of two oral sodium channel antagonists, lamotrigine and 4030W92, on intradermal capsaicin-induced hyperalgesia model.
Preclinical studies have emphasized that persistent small afferent input will induce a state of central facilitation, which can be regulated by systemically administered sodium channel blockers. We have extended these preclinical studies to the human volunteers by examining the effects of lamotrigine and 4030W92, two structurally related voltage-sensitive sodium channel antagonists, on acute sensory thresholds and facilitated processing induced by intradermal capsaicin. Fifteen healthy subjects received 4030W92, lamotrigine, and placebo in a randomized order using double-blinded crossover design methodology in three sessions each separated by a 7-day washout period. ⋯ Similarly, oral lamotrigine or 4030W92 did not alter the pain scores reported from mechanical pain stimuli at any time postcapsaicin. This study showed a lack of effect of two structurally similar sodium channel antagonists on a human experimental pain model using intradermal capsaicin, which is consistent with other studies on the effects of sodium channel antagonists of capsaicin-induced pain and hyperalgesia. This lack of effect stands in contrast to reported effects of sodium channel antagonists on preclinical models of cutaneous hyperalgesia or effects of lamotrigine on clinical neuropathic pain.
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Randomized Controlled Trial Clinical Trial
The cyclooxygenase isozyme inhibitors parecoxib and paracetamol reduce central hyperalgesia in humans.
Non-steroidal antiinflammatory drugs (NSAIDs) are known to induce analgesia mainly via inhibition of cyclooxygenase (COX). Although the inhibition of COX in the periphery is commonly accepted as the primary mechanism, experimental and clinical data suggest a potential role for spinal COX-inhibition to produce antinociception and reduce hypersensitivity. We used an experimental model of electrically evoked pain and hyperalgesia in human skin to determine the time course of central analgesic and antihyperalgesic effects of intravenous parecoxib and paracetamol (acetaminophen). ⋯ In conclusion, our results provide clear experimental evidence for the existence of central antihyperalgesia induced by intravenous infusion of two COX inhibitors, parecoxib and paracetamol. Since the electrical current directly stimulated the axons, peripheral effects of the COX inhibitors on nociceptive nerve endings cannot account for the reduction of hyperalgesia. Thus, besides its well-known effects on inflamed peripheral tissues, inhibition of central COX provides an important mechanism of NSAID-mediated antihyperalgesia in humans.
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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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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.