Pain
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Antidepressants are often used for the treatment of neuropathic pain. Clinical studies suggest that the efficacy of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRIs) for neuropathic pain is greater than that of selective 5-HT reuptake inhibitors (SSRIs). In the present study, we determined the efficacy and mechanisms involved in the antihyperalgesic effects of milnacipran, an SNRI, compared with paroxetine, an SSRI, and maprotiline, a selective NA reuptake inhibitor, using a rat model of neuropathic pain. ⋯ In microdialysis studies, NA and 5-HT concentrations in the spinal dorsal horn were increased after injection of either milnacipran or paroxetine, and only NA was increased after maprotiline. Furthermore, the NA content in the spinal cord of SNL rats was greater than that in normal animals. These findings suggest that an increase in NA in the spinal cord plays an important role in the antihyperalgesic effects of not only NA reuptake inhibitors but also SSRIs.
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Knowledge regarding mortality as a potential consequence of being sickness absent because of musculoskeletal diagnoses is almost nonexistent. The association between sickness absence because of musculoskeletal diagnoses and risk of premature death was examined in a prospective, nationwide, population-based cohort study based on Swedish registers. Included were all 4,760,987 individuals who were living in Sweden December 31, 2005, aged 20 to 64 years, and not on disability or old-age pension. ⋯ Similar associations were observed among both women and men. Moreover, increased mortality risks due to tumors (HR=1.6-1.7), circulatory diseases (HR=1.2-1.5), mental disorders (HR=1.2-3.2), and suicide (HR=1.5-1.9) were observed among persons sickness absent because of musculoskeletal diagnoses. This nationwide cohort study reveals, for the first time, an increased risk of premature death among both women and men sickness absent because of musculoskeletal diagnoses after adjustment for several potential confounders.
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We identified a patient with severe inherited erythromelalgia secondary to an L858F mutation in the voltage-gated sodium channel Na(v)1.7. The patient reported severe ongoing foot pain, which was exquisitely sensitive to limb cooling. ⋯ Robust activations of key pain, pain-affect, and reward-related centres were observed. This combined approach allowed us to confirm the presence of a temperature-sensitive channelopathy of peripheral neurons and to investigate the neural correlates of tonic neuropathic pain and relief in a single subject.