Pain
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Open-label placebos, or placebos without deception, have been found to induce analgesia, a challenging concept that need to be investigated in detail. In particular, what we need to know is the mechanism through which analgesia is induced when no deception is involved. In this study, we show for the first time that open-label placebo analgesia can be reversed by the opioid antagonist naloxone, as already shown for deceptive placebos. ⋯ In these responders, we found that a hidden injection of 10 mg naloxone could reverse placebo analgesia compared with a hidden injection of saline solution. At least 2 control groups showed that naloxone per se was not hyperalgesic, thus ruling out naloxone-induced hyperalgesia as a confounding variable. In light of the need to better understand open-label placebo effects, these findings represent the first experimental evidence that nondeceptive placebo analgesia may be mediated by the same mechanisms as deceptive placebo analgesia, namely the endogenous opioid systems.
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The increasing demand for pain management and limited resources available highlight the need to measure treatment effectiveness. We analysed data collected at 75 specialist persistent pain services located in Australia and New Zealand to calculate the overall treatment outcome for patients receiving care during 2014 to 2020. Sociodemographic and clinical information was provided for 23,915 patients, along with patient-reported measures assessing pain, pain interference, depression, anxiety, stress, pain catastrophizing, and pain self-efficacy. ⋯ Multivariable logistic regression identified those factors associated with the different groups. In particular, factors most predictive of a poor (group 4) vs good outcome (group 1) were unemployment (due to pain or other reasons), requiring an interpreter, widespread pain, pain of longer duration, and attributing the pain to an injury at work. The results may allow identification of those most likely to benefit from the services currently provided and inform development of alternative or enhanced services for those at risk of a poor outcome.
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Descending control of nociception (DCN; also known as conditioned pain modulation [CPM], the behavioral correlate of diffuse noxious inhibitory controls) is the phenomenon whereby pain inhibits pain in another part of the body and is the subject of increasing study because it may represent a biomarker of chronic pain. We recently discovered that pain modulation on the application of a DCN paradigm involving low-intensity test stimuli occurs in the direction of hyperalgesia in healthy mice and rats, whereas the use of high-intensity stimuli produces analgesia. To elucidate the physiological mechanisms underlying hyperalgesic DCN, we administered agonists and antagonists of norepinephrine (NE) and serotonin (5-HT) receptors, key neurochemical players in the production of analgesic DCN. ⋯ By contrast, analgesic DCN was found to be reversed by atipamezole and SB269970 themselves, with no effect of reboxetine or fluoxetine. Thus, hyperalgesic DCN seems to be the neurochemical opposite to analgesic DCN. These data further validate and help elucidate a preclinical paradigm that mimics dysfunctional CPM and thus may form the basis of translational experiments that aim to reveal preventative pharmacological strategies for individuals predisposed to persistent pain.
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The increased presence of senescent cells in different neurological diseases suggests the contribution of senescence in the pathophysiology of neurodegenerative disorders. Microglia can adapt to any type of disturbance of the homeostasis of the central nervous system, and its altered activity can lead to permanent and unresolvable damage. The aim of this work was to characterize the behavioural phenotype of spared nerve injury mice and then associate it with senescence-related mechanisms. ⋯ These markers were unaltered at previous time points. In murine immortalized microglial cells (BV2) stimulated with LPS 500 ng/mL for 10 days (4 hours/day) every other day, we observed an increase of β-galactosidase and senescent-associated secretory phenotype appearance, a reduction of cell viability, and an increase of senescence-associated heterochromatin foci. Therefore, present findings could represent an important step to a better understanding of the pathophysiological cellular mechanisms in comorbidities related to neuropathic pain states.