Articles: hyperalgesia.
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Opioids are frequently used for the treatment of moderate to severe acute and chronic pain. However, clinical evidence suggests that opioids can elicit increased sensitivity to noxious stimuli suggesting that administration of opioids can activate both, pain inhibitory and pain facilitatory systems. Acute receptor desensitization via uncoupling of the receptor from G proteins, upregulation of the cAMP pathway, activation of the N-methyl-D-aspartate (NMDA) receptor system and descending facilitation have been proposed as potential mechanisms underlying opioid-induced hyperalgesia. ⋯ Brief exposures to mu-receptor agonists induce long-lasting hyperalgesic effects for days. Furthermore, the prolonged use of opioids in patients often requires increasing doses and may be accompanied by the development of abnormal pain. Successful strategies that may decrease or prevent opioid-induced hyperalgesia include the concomitant administration of drugs such as NMDA antagonists, alpha(2)-agonists, or nonsteroidal anti-inflammatory drugs (NSAID), opioid rotation, or combinations of opioids with different receptor selectivity.
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Randomized Controlled Trial
Intraoperative epidural analgesia combined with ketamine provides effective preventive analgesia in patients undergoing major digestive surgery.
As a broader definition of preemptive analgesia, preventive analgesia aims to prevent the sensitization of central nervous system, hence the development of pathologic pain after tissular injury. To demonstrate benefits from preventive treatment, objective measurement of postoperative pain such as wound hyperalgesia and persistent pain should be evaluated. The current study assessed the role and timing of epidural analgesia in this context. ⋯ Combined with an antihyperalgesic dose of ketamine, intraoperative epidural analgesia provides effective preventive analgesia after major digestive surgery.
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Although opioids are unsurpassed analgesics for surgery, they also induce an N-methyl-D-aspartate-dependent enhancement of postoperative hyperalgesia. Because nitrous oxide (N2O) has anti-N-methyl-D-aspartate properties, the purpose of this study was to evaluate nitrous oxide ability to prevent such an opioid-induced hyperalgesia in rats. ⋯ Nitrous oxide, an N-methyl-D-aspartate receptor antagonist, prevented the enhancement of pain sensitivity induced by both nociceptive inputs and fentanyl and opposed acute morphine tolerance. Results suggest that perioperative nitrous oxide use reduces exaggerated postoperative pain and morphine consumption.
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The purpose of this review is to highlight the important recent advances in this fast developing field of pain mechanisms. It is now recognized that acute tissue and neural injuries can result in nociceptor sensitization (primary hyperalgesia) and spinal cord hyperexcitability or central sensitization that results in secondary hyperalgesia and allodynia. ⋯ The research of the last decade has focused on the biochemical and structural plasticity of the nervous system following tissue and nerve injury. The mechanisms involved in the transition from acute to chronic pain are complex with the involvement of interacting receptor systems and intracellular ion flux, second messenger systems, new synaptic connections and apoptosis.
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Comparative Study
5alpha-reduced neuroactive steroids alleviate thermal and mechanical hyperalgesia in rats with neuropathic pain.
5alpha-reduced neuroactive steroids with selective modulatory action in vitro on T or combined modulatory action on T and GABA(A) currents present in peripheral sensory neurons have been shown to induce potent peripheral analgesia in vivo in intact animals. Although the role of T and GABA(A) currents in pathophysiology of neuropathic pain (NPP) is not established, it appears that blockade of T currents and/or potentiation of GABA(A) currents could be beneficial in the management of NPP. To study the potential usefulness of 5alpha-reduced neuroactive steroids in alleviating NPP, we selected two newly synthesized steroids-ECN and CDNC24-with a selective blocking effect on T currents and a selective potentiating effect on GABA(A) currents, respectively, and commercial analogs-alphaxalone and 3alpha5alphaP-with the effects on both ion channels. ⋯ We found that 5alpha-reduced neuroactive steroids alleviate thermal and mechanical hyperalgesia in NPP rats. ECN and CDNC24 were more selective in alleviating thermal nociception in NPP than in sham animals when compared to 3alpha5alphaP and alphaxalone although the anti-nociceptive effect induced by 3alpha5alphaP and alphaxalone was more profound. CDNC24 was most selective since it had very minimal anti-nociceptive effect in sham animals but a very profound anti-nociceptive effect in NPP animals suggesting that, under pathological conditions, peripheral GABA(A) receptors might be an attractive therapeutic target.