Pain
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Perceived pain can be viewed because of a competition between nociceptive inputs and other competing goals, such as performing a demanding cognitive task. Task performance, however, suffers when cognitively fatigued. We therefore predicted that cognitive fatigue would weaken the pain-reducing effects of performing a concurrent cognitive task, which would indicate a causal link between fatigue and heightened pain sensitivity. ⋯ In 1 group, we induced cognitive fatigue before performing the tasks. We found that fatigue led to more pain and worse performance when the task was demanding, suggesting that fatigue weakens one's ability to distract from pain. These findings show that cognitive fatigue can impair performance on subsequent tasks and that this impairment can lower a person's ability to distract from and reduce their pain.
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Neuropilin-1 (NRP-1) is a transmembrane glycoprotein that binds numerous ligands including vascular endothelial growth factor A (VEGFA). Binding of this ligand to NRP-1 and the co-receptor, the tyrosine kinase receptor VEGFR2, elicits nociceptor sensitization resulting in pain through the enhancement of the activity of voltage-gated sodium and calcium channels. We previously reported that blocking the interaction between VEGFA and NRP-1 with the Spike protein of SARS-CoV-2 attenuates VEGFA-induced dorsal root ganglion (DRG) neuronal excitability and alleviates neuropathic pain, pointing to the VEGFA/NRP-1 signaling as a novel therapeutic target of pain. ⋯ Following in vivo editing of NRP-1, lumbar dorsal horn slices showed a decrease in the frequency of VEGFA-mediated increases in spontaneous excitatory postsynaptic currents. Finally, intrathecal injection of a lentivirus packaged with an NRP-1 guide RNA and Cas9 enzyme prevented spinal nerve injury-induced mechanical allodynia and thermal hyperalgesia in both male and female rats. Collectively, our findings highlight a key role of NRP-1 in modulating pain pathways in the sensory nervous system.
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Uncertainty pervades low back pain (LBP). This study aimed to explore individuals' experiences of navigating uncertainty when seeking care for their LBP, with a view to better understanding the contexts in which they experience uncertainty and gaining insight into how uncertainty may be better navigated during clinical encounters. We conducted 15 semistructured interviews with people who have experienced LBP. ⋯ Suggestions included making time to (actively) listen to, and acknowledge, patients' concerns; asking open-ended questions; being honest about uncertainty; creating management plans and returning to them; challenging assumptions; remaining curious about patients' context; and providing guidance on how to manage LBP rather than simply giving certainty that symptoms will worsen, lessen, or continue. These findings indicate that many of the uncertainties individuals with LBP experience are intertwined with relational aspects of their interactions with clinicians. Clinicians therefore may need to consider these broader and relational aspects of care when navigating uncertainty with people who experience LBP, bringing attention to the importance of drawing from knowledge produced outside of the usual hierarchy of evidence (eg, systematic reviews and randomised controlled trials).
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The most recent prevalence estimate of post-traumatic headache (PTH) after traumatic brain injury (TBI) in veterans and civilians dates back to 2008. The prevalence was found to be 57.8%, with surprising higher rates (75.3%) in mild TBI when compared with those with moderate/severe TBI (32.1%). However, the revision of mild TBI diagnostic criteria and an historic peak of TBI in the elderly individuals attributed to the ageing population may lead to different results. ⋯ The overall prevalence of PTH after TBI over the past 14 years remains high even if assessed only in civilians. However, the prevalence rates attributed to mild and moderate/severe TBI were similar, differing significantly from previous reports. Efforts are needed to improve TBI outcomes.