Articles: hyperalgesia.
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Randomized Controlled Trial Clinical Trial
Analgesic and antihyperalgesic effects of nabilone on experimental heat pain.
In this study, we explored the analgesic and antihyperalgesic properties of a synthetic cannabinoid (nabilone) on experimental heat pain in men and women, as well as its effects on descending pain inhibitory systems. ⋯ Nabilone failed to produce analgesic effects and it did not interact with descending pain inhibitory systems. However, we found that a single 1 mg dose of nabilone reduced temporal summation for women but not men. Although a titration regime and a larger sample of subjects might have provided more robust effects, these preliminary results suggest that nabilone appears effective at relieving hyperalgesic responses in women. Possible neurobiological mechanisms and clinical implications are further discussed.
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Randomized Controlled Trial
Pharmacological dissection of the paradoxical pain induced by a thermal grill.
We investigated the role of the glutamatergic and endogenous opioidergic systems in the paradoxical pain evoked by the simultaneous application of innocuous warm and cold stimuli to the skin with a "thermal grill". Two parallel randomized, double-blind, cross-over studies, including two groups of 12 healthy volunteers, were carried out to compare the effects of i.v. ketamine or naloxone to those of placebo, on the sensations produced by a thermode (i.e. thermal grill) composed of six bars applied on the palmar surface of the right hand. The temperature of alternate (even- and odd-numbered) bars could be controlled independently by Peltier elements to produce various patterns of the grill. ⋯ By contrast, naloxone had no effect on paradoxical pain, normal pain or non-painful thermal sensations. This study demonstrates for the first time that the "thermal grill illusion of pain" can be modulated pharmacologically. This paradoxical pain, which involves the glutamatergic systems, acting through the NMDA receptors, but not the tonic endogenous opioids systems, might share some mechanisms with pathological pain.
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Randomized Controlled Trial
Antihyperalgesic and analgesic properties of the N-methyl-D-aspartate (NMDA) receptor antagonist neramexane in a human surrogate model of neurogenic hyperalgesia.
NMDA-receptors are a major target in the prevention and treatment of hyperalgesic pain states in neuropathic pain. However, previous studies revealed equivocal results depending on study design and efficacy parameters. We tested the analgesic (generalized reduction of generation and processing of nociceptive signalling) and anti-hyperalgesic (prevention of central sensitization) properties of the NMDA-receptor antagonist neramexane and the potassium channel opener flupirtine in the intradermal capsaicin injection model. ⋯ The results suggests that in a human surrogate model of neurogenic hyperalgesia a single low-dose of neramexane had a marked analgesic effect in the sensitized and in the non-sensitized state and thus may be a useful drug to treat the enhanced pain sensitivity in neuropathic pain patients. Its efficacy may be based on analgesia rather than anti-hyperalgesia or anti-windup. In contrast, flupirtine showed neither an analgesic nor an anti-hyperalgesic effect at a dose used for the treatment of postoperative pain.
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Randomized Controlled Trial
Sleep deprivation is hyperalgesic in patients with gastroesophageal reflux disease.
Studies have demonstrated that gastroesophageal reflux disease (GERD) can cause sleep deprivation because of nighttime heartburn or short, amnestic arousals during sleep. Sleep deprivation has been associated with reports of increased GERD severity. Our aim was to determine whether sleep deprivation enhances perception of intraesophageal acid in patients with GERD vs healthy controls. ⋯ Sleep deprivation is hyperalgesic in patients with GERD and provides a potential mechanism for increase in GERD symptom severity in sleep-deprived patients.
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Randomized Controlled Trial
The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans.
TRPV1 is a cation channel activated by a range of noxious stimuli and highly expressed in nociceptive fibres. TRPV1 receptors are involved in pain and sensitisation associated with tissue injury and inflammation; hence, TRPV1 antagonists are potentially useful for the treatment of such pain states. SB-705498 is a potent, selective and orally bioavailable TRPV1 antagonist with demonstrated efficacy in a number of preclinical pain models. ⋯ The magnitude of the pharmacodynamic effects of SB-705498 appeared to be related to plasma concentration. These results indicate that SB-705498, at a clinically safe and well-tolerated dose, has target-specific pharmacodynamic activity in humans. These data provide the first clinical evidence that a TRPV1 antagonist may alleviate pain and hyperalgesia associated with inflammation and tissue injury.