Articles: opioid.
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Duloxetine is a serotonin-norepinephrine reuptake inhibitor prescribed for musculoskeletal and other forms of chronic pain. Its dual pharmacologic properties have the potential to either raise or lower cardiovascular risk: adrenergic activity may increase the risk for acute myocardial infarction (AMI) and stroke, but antiplatelet activity may decrease risk. Gabapentin is another nonopioid medication used to treat pain, which is not thought to have adrenergic/antiplatelet effects. With the current emphasis on the use of nonopioid medications to treat patients with chronic pain, assessing cardiovascular risks associated with these medications among high-risk patients is important. ⋯ In summary, cohort Medicare patients with non-cancer pain beginning treatment with duloxetine had rates of AMI, stroke, and out-of-hospital mortality comparable to those who initiated gabapentin.
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The nucleus of the solitary tract (NTS) contains pro-opiomelanocortin (POMC) neurons that are 1 of the 2 major sources of β-endorphin in the brain. The functional role of these NTS POMC neurons in nociceptive and cardiorespiratory function is debated. We have shown that NTS POMC optogenetic activation produces bradycardia and transient apnoea in a working heart-brainstem preparation and chemogenetic activation with an engineered ion channel (PSAM) produced opioidergic analgesia in vivo. ⋯ Inhibiting NTS POMC neurons does not produce any effect on basal nociception but inhibits stress-induced analgesia (unlike inhibition of arcuate POMC neurons). Activation of NTS POMC neuronal populations in conscious mice did not cause respiratory depression, anxiety, or locomotor deficit (in open field) or affective preference. These findings indicate that NTS POMC neurons play a key role in the generation of endorphinergic endogenous analgesia and can also regulate cardiorespiratory function.