Pain
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Recent studies suggest that opioids can produce analgesia through peripheral mechanisms following inflammation of peripheral tissue. This study examined whether opioids administered prior to inflammation can produce antinociception by peripheral mechanisms in a model of visceral pain. Mice were injected intraperitoneally (i.p.) with 1% acetic acid to evoke abdominal writhing, a standard model of visceral pain. ⋯ The highest dose (10 microg) was ineffective when given intravenously 5 min before acetic acid, suggesting that antinociception following i.p. administration was acting via peripheral mechanisms. These data demonstrate that low doses of opioids, given before or after acetic acid, produce visceral antinociception through peripheral mechanisms. This may be clinically relevant for the management of postoperative abdominal pain.
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Anatomical studies demonstrate the presence of glutamate receptors on unmyelinated axons in peripheral cutaneous nerves. Pharmacological studies show that intraplantar injection of glutamate or glutamate agonists in the glabrous skin results in nociceptive behaviors. The present study describes a novel in vitro skin-nerve preparation using the glabrous skin from the rat hindpaw. ⋯ Exposure of A delta or C fibers to glutamate did not result in a decrease in von Frey thresholds. These data provide a physiological basis for the nociceptive behaviors that arise following intraplantar injection of glutamate or glutamate agonists. Furthermore, demonstration of glutamate-induced excitation and heat sensitization of nociceptors indicates that local or topical administration of glutamate receptor antagonists may have therapeutic potential for the treatment of pain.
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Nerve growth factor (NGF) regulates the nociceptive properties including sensitivity to capsaicin of a subset of dorsal root ganglion neurons, which express the high-affinity NGF receptor, trkA. Capsaicin sensitivity co-localizes with the expression of a cloned capsaicin receptor, vanilloid receptor type 1 (VR-1), which displays properties similar to the native capsaicin response. ⋯ NGF treatment increased both VR-1 mRNA expression and capsaicin evoked release of CGRP. These effects were inhibited by treatment with the trkA inhibitor k252a.
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Randomized Controlled Trial Clinical Trial
Expectations of analgesia do not affect spinal nociceptive R-III reflex activity: an experimental study into the mechanism of placebo-induced analgesia.
The purpose of this study was to investigate whether placebo analgesia is mediated by the release of beta-endorphin. In addition to subjective pain reports, we included an objective physiological parameter of nociception reflected by the opioid sensitive nociceptive R-III reflex. Placebo consisted of strong suggestions of pain relief and an intravenous injection of saline. ⋯ Consistently, the antagonizing effects of naloxone were negligible. A subgroup analysis of those who did show a placebo response as indicated on the VAS did not support the supposition that beta-endorphin is released due to placebo suggestion. It is suggested that intensified stimuli and a more effective procedure to induce placebo analgesia (e.g. conditioning) may produce a proper placebo effect.
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Recent animal studies using stress-induced analgesia have suggested a general age-related decline in endogenous pain inhibitory systems. The aim of the current study was to examine age-related differences in the magnitude of endogenous analgesia in human volunteers, using psychophysical measures of neuroselective electrical, and thermal CO(2) laser induced pain thresholds, before, immediately after and 1 h after repeated cold water immersion of the hand. Sensory detection thresholds did not differ between age groups indicating that the functional integrity of primary afferent sensory fibres appears to be intact in older people. ⋯ This effect was relatively transient with thresholds returning to baseline within 1 h. The magnitude of analgesic response, however, was found to be significantly less in older people. Age differences in the efficacy of endogenous analgesic systems may be expected to reduce the ability of older adults to cope with severe persistent pain states and may help explain some of the variation in the literature on pain report.