Pain
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Physical activity has multiple health benefits but may also increase the risk of developing musculoskeletal pain (MSP). However, the relationship between physical activity and MSP has not been well characterized. This study examined the dose-response relationship between sports activity and MSP among adolescents. ⋯ In longitudinal analysis, the risk ratio for developing pain at 1-year follow-up per 1 h/wk increase in baseline sports activity was 1.03 (95% confidence interval = 1.02-1.05). Spline models indicated a linear association (P < 0.001) but not a nonlinear association (P ≥ 0.45). The more the adolescents played sports, the more likely they were to have and develop pain.
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We reported earlier that TNF-α, a proinflammatory cytokine implicated in many inflammatory disorders causing orofacial pain, increases the activity of Cdk5, a key kinase involved in brain development and function and recently found to be involved in pain signaling. To investigate a potential mechanism underlying inflammatory pain in trigeminal ganglia (TGs), we engineered a transgenic mouse model (TNF) that can conditionally overexpresses TNF-α upon genomic recombination by Cre recombinase. TNF mice were bred with Nav1.8-Cre mouse line that expresses the Cre recombinase in sensory neurons to obtain TNF-α:Nav1.8-Cre (TNF-α cTg) mice. ⋯ Remarkably, this effect was prevented by roscovitine, an inhibitor of Cdk5, which suggests that TNF-α overexpression induced sensitization of the TRPV1 channel. Furthermore, TNF-α cTg mice displayed more aversive behavior to noxious thermal stimulation (45°C) of the face in an operant pain assessment device as compared with control mice. In summary, TNF-α overexpression in the sensory neurons of TNF-α cTg mice results in inflammatory sensitization and increased Cdk5 activity; therefore, this mouse model would be valuable for investigating the mechanism of TNF-α involved in orofacial pain.
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Plasticity in inhibitory receptors, neurotransmission, and networks is an important mechanism for nociceptive signal amplification in the spinal dorsal horn. We studied potential changes in GABAergic pharmacology and its underlying mechanisms in hyperalgesic priming, a model of the transition from acute to chronic pain. We find that while GABAA agonists and positive allosteric modulators reduce mechanical hypersensitivity to an acute insult, they fail to do so during the maintenance phase of hyperalgesic priming. ⋯ Neurolide 2 treatment also reverses the change in polarity in GABAergic pharmacology observed in the maintenance of hyperalgesic priming. We propose that increased nlgn2 expression is associated with hyperalgesic priming where it promotes dysregulation of inhibitory networks. Our observations reveal new mechanisms involved in the spinal maintenance of a pain plasticity and further suggest that disinhibitory mechanisms are central features of neuroplasticity in the spinal dorsal horn.