Pain
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The loss of GABAergic inhibition is a mechanism that underlies neuropathic pain. Therefore, rescuing the GABAergic inhibitory tone through the activation of GABA A receptors is a strategy to reduce neuropathic pain. This study was designed to elucidate the function of the spinal α 6 -containing GABA A receptor in physiological conditions and neuropathic pain in female and male rats. ⋯ Finally, α 6 subunit is expressed in humans. This receptor is found in CGRP + and P2X3 + primary afferent fibers but not astrocytes in the human spinal dorsal horn. Our results suggest that the spinal α 6 -containing GABA A receptor has a sex-specific antinociceptive role in neuropathic pain, suggesting that this receptor may represent an interesting target to develop a novel treatment for neuropathic pain.
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Pain management for patients with dementia is challenging because many experience pain while being unable to communicate their pain. The aim of this study was to describe pain, pain management, and to perform a thorough clinical examination of chronic pain conditions among patients with dementia. Residents (n = 498) from 12 nursing homes were assessed for dementia (Clinical Dementia Rating scale [CDR]) and for pain with the Mobilization-Observation-Behavior-Intensity-Dementia-2 (MOBID-2) assessment form. ⋯ Chronic widespread pain was the most prevalent (14.5%) followed by nonspecific pain from the back (13.4%), whereas the most prevalent chronic secondary pain conditions were chronic pain caused by osteoarthritis (15.4%) and stroke (8.0%). One-fourth received opioids, which was significantly associated with severe pain ( P < 0.001) compared with moderate pain, although no significant association was found between opioid use and the type of pain condition. Although knowledge of the severity and specific types of pain conditions is recommended to direct the choice of treatment, these areas are not sufficiently explored in the nursing home populations with dementia and may hinder a better treatment of pain in this population.
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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.