Pain
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Pain is known to interrupt attentional performance. Such interference effects seem to occur preferentially for tasks that are complex and/or difficult. However, few studies have directly manipulated memory load in the context of pain interference to test this view. ⋯ These results suggest that while cognitive load may influence the interruptive effect of pain on attention, this effect may be selective. Because pain affected the high-load version of the n-back task but did not interrupt performance on attentional switching or dual-task paradigms, this means that our findings did not completely support our hypotheses. Future research should explore further the parameters and conditions under which pain-related interference occurs.
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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.
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The dynamics of noxious sensation shapes pain perception, yet the memory of the temporal dimension of pain remains almost completely unexplored. Here, brain activity during the memory of pain duration was contrasted with that associated with the memory of pain intensity using functional magnetic resonance imaging and a delayed reproduction task. Participants encoded, maintained during a short delay, and reproduced (1) the "duration" of pain (ie, onset-to-offset), (2) the "dynamics" of pain (ie, evolution of pain over time), or (3) the intensity of pain (ie, control with no explicit temporal processing required). ⋯ In contrast, the memory delay of the dynamic task involved the bilateral supplementary motor area and the frontoparietal attentional network. Although SI, SII, and insula may contribute to the memory trace of pain sensation, other areas less commonly reported in pain studies are associated with time processing and may therefore contribute to the processing of temporal aspects of pain. Results further suggest a differential role of core timing regions of the brain depending on specific task instructions and attentional allocations to the single dimension of time, as compared to the joint processing of both time and intensity.
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Along with the well-known rewarding effects, activation of nicotinic acetylcholine receptors (nAChRs) can also relieve pain, and some nicotinic agonists have analgesic efficacy similar to opioids. A major target of analgesic drugs is the descending pain modulatory pathway, including the ventrolateral periaqueductal gray (vlPAG) and the rostral ventromedial medulla (RVM). Although activating nAChRs within this circuitry can be analgesic, little is known about the subunit composition and cellular effects of these receptors, particularly within the vlPAG. ⋯ Furthermore, intra-vlPAG α7 antagonist pretreatment blocked PHA-543,613-induced antinociception via either administration method. Systemic administration of submaximal doses of the α7 agonist and morphine produced additive antinociceptive effects. Together, our findings indicate that the vlPAG is a key site of action for α7 nAChR-mediated antinociception.
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Long noncoding RNAs have been implicated in neuropathy. Here, we identify and validate a long noncoding RNA, MRAK009713, as the primary regulator of neuropathic pain in chronic constriction injury (CCI) rats. MRAK009713 expression was markedly increased in CCI rats associated with enhanced pain behaviors, and small interfering RNA against MRAK009713 significantly reduced both mechanical and thermal hyperalgesia in the CCI rats. ⋯ Overexpression of MRAK009713 markedly increased expression of P2X3 in the dorsal root ganglia of the control rats, and MRAK009713 small interfering RNA significantly inhibited the P2X3 expression in the dorsal root ganglia of the CCI rats. MRAK009713 directly interacted with the P2X3 protein heterologously expressed in the human embryonic kidney (HEK) 293 cells and potentiated P2X3 receptor function. Thus, MRAK009713 is a novel positive regulator of neuropathic pain in rats through regulating the expression and function of the P2X3 receptor.