Pain
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Several studies implicated cyclic adenosine monophosphate (cAMP) as an important second messenger for regulating nociceptor sensitization, but downstream targets of this signaling pathway which contribute to neuronal plasticity are not well understood. We used a Cre/loxP-based strategy to disable the function of either HCN2 or PKA selectively in a subset of peripheral nociceptive neurons and analyzed the nociceptive responses in both transgenic lines. ⋯ Facilitation of Ih via cAMP, a hallmark of the Ih current, was abolished in neurons without PKA activity. Collectively, these results show a significant contribution of both genes to inflammatory pain and suggest that PKA-dependent activation of HCN2 underlies cAMP-triggered neuronal sensitization.
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Review Meta Analysis
Persistent postoperative pain after cardiac surgery: a systematic review with meta-analysis regarding incidence and pain intensity.
Persistent postoperative pain (PPP) has been described as a complication of cardiac surgery (CS). We aimed to study PPP after CS (PPPCS) by conducting a systematic review of the literature regarding its incidence, intensity, location, and the presence of neuropathic pain, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The review comprised 3 phases: a methodological assessment of 6 different databases identifying potential articles and screening for inclusion criteria by 2 independent reviewers; data extraction; and study quality assessment. ⋯ Chest is the main location of PPPCS followed by the leg; neuropathic pain is present in the majority of the patients. This is the first systematic review and meta-analysis to provide estimates regarding incidence and intensity of PPPCS, which elucidates its relevance. There is an urgent need for adequate treatment and follow-up in patients with PPPCS.
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Review Meta Analysis
Most red flags for malignancy in low back pain guidelines lack empirical support; a systematic review.
Clinicians do not want to miss underlying serious pathology, but it is still unclear which red flags are relevant. We aimed to evaluate the origin and evidence on diagnostic accuracy of red flags for malignancy for management of low back pain (LBP) in primary care. We performed a comprehensive overview and searched the literature using snowballing techniques and reference checking for evidence on red flags endorsed in clinical guidelines for identifying patients with higher likelihood of malignancy. ⋯ We found 5 red flags with accuracy data from 2 or more studies, with 2 ("history of malignancy" and "strong clinical suspicion") considered informative. In conclusion, the origin and diagnostic accuracy of many red flags endorsed in guidelines are unclear. A "history of malignancy" and "strong clinical suspicion" are the only red flags with empirical evidence of acceptably high diagnostic accuracy.