Pain
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Comparative Study
Disturbances in slow-wave sleep are induced by models of bilateral inflammation, neuropathic, and postoperative pain, but not osteoarthritic pain in rats.
Preclinical assessment of pain has typically relied on measuring animal responses to evoked stimulation. Because of inherent limitations of these assays, there is a need to develop measures of animal pain/discomfort that are objective, not experimentally evoked, and mimic the human condition. Patients with chronic pain manifest a variety of co-morbidities, one of which is disturbances in sleep. ⋯ Sleep disturbances lasted for approximately 3 to 14days, depending on the model, and were resolved despite continued hypersensitivity to evoked stimulation. Morphine, gabapentin, diclofenac, and ABT-102 (TRPV1 antagonist) all improved sleep in the bilateral CFA assay at doses that did not significantly alter SWS in uninjured rats. Preclinical assessment of compounds should follow the path of clinical studies and take into account diverse aspects of the "pain condition." This would include evaluating nociceptive thresholds as well as other endpoints, such as cognition and sleep, that may be affected by the pathological state.
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Chronic musculoskeletal complaints (MSCs) are among the major health problems, and cross-sectional studies suggest an association between smoking and MSCs. The causal relationship, however, is not known. The present study is designed to assess the association between smoking and chronic MSCs, and is based on data from a large longitudinal cohort study of all inhabitants ⩾20years in Nord-Trøndelag County (Helse Undersøkelsen i Nord-Trøndelag -HUNT), conducted in 1995-97 (HUNT 2) and 2006-08 (HUNT 3). ⋯ The results show that smoking at baseline represents a 20% increased risk (IRR=1.20, 95% CI 1.14-1.27, P=0.0001) for chronic MSCs at follow-up. The risk for chronic MSCs by daily smoking decreased with increasing age up to 50years; after this, there was no significant association. The results show that modifiable risk factors like smoking should be included in public health intervention programs for MSCs.
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Randomized Controlled Trial
The extent of neurocognitive dysfunction in a multidisciplinary pain centre population. Is there a relation between reported and tested neuropsychological functioning?
Patients with chronic nonmalignant pain syndromes frequently report cognitive dysfunction, in particular with respect to concentration and attention. Such complaints have, in general, been attributed to depressive symptoms. In this study we showed that cognitive complaints in chronic pain patients are significantly associated with objective test performance in the area of inhibitory control after partialling out degree of depressive symptoms. ⋯ A larger proportion of patients with generalized and neuropathic pain performed below this cut-off, whereas patients with localized pain exhibited impaired function to a lesser degree. Chronic pain patients receiving opioids did not perform worse than patients off opioid treatment. Systematic assessment of basic neurocognitive functions in centres treating chronic pain patients is warranted.
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Mammalian target of rapamycin complex 1 (mTORC1) inhibitors are extensively used as immunosuppressants to prevent transplant rejection and in treatment of certain cancers. In patients, chronic treatment with rapamycin or its analogues (rapalogues) has been reported to lead to sensory hypersensitivity and pain conditions via an unknown mechanism. Here, we show that pharmacological or genetic inhibition of mTORC1 activates the extracellular signal-regulated kinase (ERK) pathway in sensory neurons via suppression of S6K1 to insulin receptor substrate 1 negative feedback loop. ⋯ Taken together, our findings demonstrate that activation of the ERK pathway in sensory neurons as a consequence of mTORC1 inhibition leads to the development of pain. Importantly, this effect is abolished by co-treatment with metformin, thus providing a potential treatment option for rapalogue-evoked pain. Our findings highlight the physiological relevance of feedback signaling through mTORC1 inhibition and have important implications for development of pain therapeutics that target the mTOR pathway.
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Estrogen status and psychological stress contribute to the expression of several chronic pain conditions including temporomandibular muscle and joint disorders (TMJD). Sensory neurons that supply the temporomandibular joint (TMJ) region terminate in laminae I and V of the spinal trigeminal nucleus (Vc/C1-2 region); however, little is known about lamina-specificity and environmental influences on the encoding properties of TMJ brainstem neurons. To test the hypothesis that Vc/C1-2 neurons integrate both interoceptive and exteroceptive signals relevant for TMJ nociception, we recorded TMJ-evoked activity in superficial and deep laminae of ovariectomized rats under high and low estradiol (E2) and stress conditions. ⋯ By contrast, FS conditioned rats displayed increased background firing and TMJ-evoked activity of neurons in deep, but not superficial, laminae independent of E2 status. FS also enhanced TMJ-evoked masseter muscle activity and suggested the importance of deep dorsal horn neurons in mediating evoked jaw muscle activity. In conclusion, E2 status and psychophysical stress play a significant role in modifying the encoding properties of TMJ-responsive medullary dorsal horn neurons with a marked lamina-specificity.