Pain
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Brain biomarkers of pain, including pain-predictive "signatures" based on brain activity, can provide measures of neurophysiological processes and potential targets for interventions. A central issue relates to the specificity of such measures, and understanding their current limits will both advance their development and explore potentially generalizable properties of pain to other states. Here, we used 2 data sets to test the neurologic pain signature (NPS), an established pain neuromarker. ⋯ Local NPS patterns in anterior or midinsula, S2, and dorsal anterior cingulate responded to breathlessness and finger opposition and were reduced by remifentanil. Local NPS responses in the dorsal posterior insula did not respond to any manipulations. Therefore, significant global NPS activity alone is not specific for pain, and we offer insight into the overlap between NPS responses, breathlessness, and somatomotor demand.
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Chronic pain is a highly prevalent and severely disabling disease that is associated with substantial changes of brain function. Such changes have mostly been observed when analyzing static measures of resting-state brain activity. However, brain activity varies over time, and it is increasingly recognized that the temporal dynamics of brain activity provide behaviorally relevant information in different neuropsychiatric disorders. ⋯ As microstate D has previously been related to attentional networks and functions, these abnormalities might relate to dysfunctional attentional processes in chronic pain. Subgroup analyses replicated microstate D changes in patients with chronic back pain, while patients with chronic widespread pain did not show microstates alterations. Together, these findings add to the understanding of the pathophysiology of chronic pain and point to changes of brain dynamics specific to certain types of chronic pain.
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Tricyclic antidepressants that inhibit serotonin and noradrenaline reuptake, such as amitriptyline, are among the first-line treatments for neuropathic pain, which is caused by a lesion or disease affecting the somatosensory nervous system. These treatments are, however, partially efficient to alleviate neuropathic pain symptoms, and better treatments are still highly required. Interactions between neurons and glial cells participate in neuropathic pain processes, and importantly, connexins-transmembrane proteins involved in cell-cell communication-contribute to these interactions. ⋯ Another connexin blocker, carbenoxolone, also improved amitriptyline action. Additional in vitro studies suggested that mefloquine may also directly act on serotonin transporters and on adenosine A1 and A2A receptors, but drugs acting on these other targets failed to amplify amitriptyline action. Together, our data indicate that pharmacological blockade of connexins potentiates the therapeutic effect of amitriptyline in neuropathic pain.
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Endogenous opioids mediate the pleasurable responses to positively reinforcing stimuli such as palatable food. Yet, the reduction or omission of a negative experience can also be rewarding (negative reinforcement). As such, pain relief leads to negative reinforcement and evokes a pleasant feeling in humans. ⋯ Endogenous opioid blockade by naltrexone decreased relief and pleasantness ratings compared with placebo (P = 0.0027). This study provides evidence that endogenous opioids play a role in mediating the pleasant feeling of pain relief in humans. Clinically, the rewarding nature of pain relief and its underlying mechanisms require consideration because of their potential reinforcing effects on behaviors that might be beneficial short-term but maladaptive long-term.