Pain
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The experience of pain associated with labour is complex and challenging to assess. A range of pain measurement tools are reported in the literature. This review aimed to identify current tools used in research to assess labour pain across the past decade and to evaluate their implementation and adequacy when used in the context of labour pain. ⋯ Numerous variations in the implementation of scales were noted. This included 35 variations found in the wording of the upper and lower anchors of the Visual Analogue Scale, some assessment tools not allowing an option for "no pain," and instances where only sections of validated tools were used. It is clear that development of a standardised pain assessment strategy, which evaluates the multidimensions of labour pain efficiently and effectively and allows for both positive and negative experiences of pain to be reported, is needed.
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Prognostic prediction models for 3 different definitions of nonrecovery were developed in the Back Complaints in the Elders study in the Netherlands. The models' performance was good (optimism-adjusted area under receiver operating characteristics [AUC] curve ≥0.77, R2 ≥0.3). This study aimed to assess the external validity of the 3 prognostic prediction models in the Norwegian Back Complaints in the Elders study. ⋯ Recalibration yielded acceptable calibration for both models, according to the calibration plots. Step 3 did not improve performance substantially. The recalibrated models may need further external validation, and the models' clinical impact should be assessed.
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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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Insight into nociceptive circuits will ultimately build our understanding of pain processing and aid the development of analgesic strategies. Neural circuit analysis has been advanced greatly by the development of optogenetic and chemogenetic tools, which have allowed function to be ascribed to discrete neuronal populations. Neurons of the dorsal root ganglion, which include nociceptors, have proved challenging targets for chemogenetic manipulation given specific confounds with commonly used DREADD technology. ⋯ We also demonstrated that our strategy can effectively silence inflammatory-like pain in a chemical pain model. Collectively, we have generated a novel tool that can be used to selectively silence defined neuronal circuits in vitro and in vivo. We believe that this addition to the chemogenetic tool box will facilitate further understanding of pain circuits and guide future therapeutic development.
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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).