Articles: hyperalgesia.
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The aim of this study was to investigate the role of endogenous enkephalin in the cerebral antihyperalgesic action of gabapentin. Neuropathic pain models and antihyperalgesic effect of gabapentin were confirmed by the presentation and changes of mechanical allodynia and thermal hyperalgesia of operated mouse hind paws. The results suggested that endogenous enkephalin may not be involved in the antihyperalgesic effect of gabapentin.
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Pharmacol. Biochem. Behav. · Dec 2010
Intrathecal administration of a gap junction decoupler, an inhibitor of Na(+)-K(+)-2Cl(-) cotransporter 1, or a GABA(A) receptor agonist attenuates mechanical pain hypersensitivity induced by REM sleep deprivation in the rat.
We studied the hypothesis that some of the spinal mechanisms that are involved in neuropathic hypersensitivity play a role in hypersensitivity induced by REM sleep deprivation (REMSD). Rats with a chronic intrathecal (i.t.) catheter had REMSD of 48h duration that induced hypersensitivity to mechanical stimulation. After REMSD, the animals were treated i.t. with carbenoxolone (a gap junction decoupler), bumetanide (a blocker of Na(+)-K(+)-2Cl(-) cotransporter 1 or NKCC1), muscimol (a GABA(A) receptor agonist), or pretreated intraperitoneally with minocycline (an inhibitor of microglia activation). ⋯ The results suggest that among spinal pain facilitatory mechanisms that are common to REMSD and neuropathy are NKCC1 blocker- and gap junction decoupler-reversible mechanisms. Moreover, there is a net pain inhibitory effect by spinal administration of an exogenous GABA(A) receptor agonist following REMSD as shown earlier in neuropathy. In contrast, activation of spinal microglia may not be as important for the development of hypersensitivity induced by REMSD as following nerve injury.
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Randomized Controlled Trial
A pharmacokinetic and pharmacodynamic study of oral oxycodone in a human experimental pain model of hyperalgesia.
Oxycodone is not as well characterized, with respect to its pharmacokinetic/pharmacodynamic properties, as other opioids. Moreover, the pharmacodynamic profile of oxycodone can be affected by changes in the pain system, e.g. hyperalgesia. Therefore, the aim of this study was to investigate the pharmacokinetic/pharmacodynamic profiles of oxycodone in a human experimental pain model of hyperalgesia. ⋯ There was a measurable effect of oxycodone, compared with placebo, on all pain measures, and a linear concentration-effect relationship without an effect delay was demonstrated. This could indicate an initial peripheral analgesic effect of oxycodone.
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Understanding the actions of opioids now encompasses pronociceptive as well as antinociceptive mechanisms. Opioid-induced hyperalgesia (OIH) refers to increased pain sensitivity due to high-dose or prolonged opioid exposure. It has become more important as patients with pain remain on opioids at higher doses for longer periods of time. One setting that highlights the dilemma of OIH is in the opioid-tolerant patient who is hospitalized for painful medical conditions or procedures and is unable to achieve adequate analgesia despite escalating opioid doses. This patient population often requires agents that act synergistically with opioids through different mechanisms to achieve analgesia. Dexmedetomidine is an alpha-2 adrenergic agonist that has been shown to synergize with opioids. ⋯ The cases presented provide support for the clinical utility of alpha-2 agonists during opioid dose reduction in patients with OIH as well suggesting that they may contribute to the recovery of normal nociceptive and antinociceptive responses.
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Reproductive sciences · Dec 2010
Generalized hyperalgesia in women with endometriosis and its resolution following a successful surgery.
Although pains of various kinds top the list of complaints from women with endometriosis and are the most debilitating of the disease, little is known about the mechanism/mechanisms of endometriosis-associated pains. To test the hypothesis that women with endometriosis have generalized hyperalgesia which may be alleviated by a successful surgery, we recruited 100 patients with surgically and histologically confirmed endometriosis and 70 women without, and tested their responses to pain stimulations. Before the surgery, all patients rated their dysmenorrhea severity by Visual Analog scale (VAS) and went through an ischemic pain test (IPT) and an electrical pain test (EPT). ⋯ We found that patients with endometriosis had significantly higher IPT VAS scores and lower EPT pain threshold than controls, but after surgery their IPT scores and EPT pain threshold were significantly and progressively improved, along with their dysmenorrhea severity. Thus, we conclude that women with endometriosis have generalized hyperalgesia, which was alleviated by surgery. Consequently, central sensitization may be a possible mechanism underlying various forms of pain associated with endometriosis, and its recognition should have important implications for the development of novel therapeutics and better clinical management of endometriosis.