Pain
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In view of the need for valid, reliable, and clinically useful scales to assess pain in elderly people with dementia, this study evaluated the psychometric properties of translated versions of the PAINAD, PACSLAC, and DOLOPLUS-2 scales. In an observational study design, two raters simultaneously assessed the nursing home residents (n=128) for pain during influenza vaccination and care situations. The PACSLAC was valued as the most useful scale by nurses. ⋯ IC of the DOLOPLUS were adequate for the total scale (alpha ranged .74-.75) and almost all subscales (alpha ranged .58-.80). Findings of this study provide evidence of validity and reliability of the three pain assessment scales. Now that a pain scale is available, future studies also need to focus on its implementation in nursing practice.
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Our previous recordings from dorsal root ganglion and spinal lamina V neurons from TRPV1-mutant mice showed dramatic decreases in responses to temperatures near the activation threshold of this channel (43-49 degrees C). Somewhat unexpectedly, we only observed behavioral deficits in these mice at higher temperatures (50-58 degrees C). In the present study, we tested the hypothesis that the noxious heat-evoked pain behavior that persists in TRPV1-mutant mice reflects residual responsiveness of neurons in the superficial, but not deep, dorsal horn. ⋯ We conclude that TRPV1 is necessary for noxious heat-evoked responses of lamina V neurons, both before and after tissue injury. It is also an essential contributor to the normal activation threshold of lamina I neurons to noxious heat and for the full duration of thermal sensitization of lamina I neurons following injury. Finally, our results suggest that the processing of noxious thermal messages by neurons in lamina I involves convergent inputs from a heterogeneous population of primary afferent thermal nociceptors.
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Inflammation, peripheral nerve injury and chemical irritants can cause central sensitization in pain pathways. Prostaglandins produced in the CNS induce central sensitization during inflammation mainly by relieving nociceptive neurons from glycinergic inhibition. We have recently identified spinal prostaglandin E receptors of the EP2 subtype (EP2 receptors) and the glycine receptor alpha3 subunit (GlyR alpha3) as signal transduction elements involved in the generation of central inflammatory hyperalgesia. ⋯ The lack of a phenotype in GlyR alpha3-/- mice together with the absence of a facilitating effect of intrathecal PGE2 on formalin-induced nociception in wild-type mice suggests that peripheral rather than spinal EP2 receptors are involved. These results indicate that inhibition of glycinergic neurotransmission by EP2 receptor activation does not contribute to pain following peripheral nerve injury or chemical irritation with formalin. Our results thus provide further evidence that inflammatory hyperalgesia and neuropathic pain involve different mechanisms of central sensitization.
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Studies implicate endocannabinoids in the acute and chronic actions of opioid drugs, including the genesis of physical dependence. Previous evidence suggests that spinal release of calcitonin gene-related peptide (CGRP) and activation of its receptors contribute to opioid physical dependence. The release of CGRP at the spinal level is modulated by cannabinoid (CB1)-receptors. ⋯ Intrathecal co-administration of CB1-receptor antagonists, AM-251 or SR141716A, with daily morphine attenuated the behavioral manifestations of withdrawal. Treatment with AM-251 also reduced the depletion of CGRP, suppressed Fos-induction, and prevented the increase in capsaicin-evoked spinal CGRP release. Altogether, this study suggests that endocannabinoid activity, expressed via CB1-receptors, contributes to the induction of opioid physical dependence through spinal modulation of CGRP.
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Randomized Controlled Trial
Differential sensitivity of three experimental pain models in detecting the analgesic effects of transdermal fentanyl and buprenorphine.
This is the first randomized controlled trial that tests the analgesic efficacy of transdermally delivered opioids in healthy volunteers and that assesses the sensitivity of different experimental pain tests to detect analgesia in this setting. Transdermal application of the full agonist fentanyl (TDF: 12.5 or 25 microg/h) and the partial agonist buprenorphine (TDB: 35 microg/h) was compared in three experimental models of acute pain (heat pain, painful electrical stimulation, cold pressor) in a double-blind, randomized, placebo-controlled, 4-arm crossover study with 20 healthy subjects (15 men, 5 women). Patches were administered for 72 h and pain levels measured at baseline and 24 and 72 h, with an 11-day wash-out. ⋯ We conclude that the cold pressor test was most sensitive to analgesic effects in healthy subjects and that a transdermal dose of 12.5 microg/h fentanyl achieved significant pain reduction compared with placebo. Subjects experienced opioid-typical AEs including dizziness, nausea and vomiting. No serious AEs occurred.