Pain
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Sex differences in pain become apparent during puberty. However, the influence of key pubertal characteristics and pubertal hormones on pain is largely unknown. We examined the prospective associations between self-reported and hormone-indicated pubertal characteristics and pain incidence and severity in 10- to 11-year-old pain-free youth in the Adolescent Brain Cognitive Development (ABCD) Study over 1 year. ⋯ In boys, higher PDS item variance was associated with greater pain incidence (RR = 1.11, 95% CI, 1.03-1.20) and interference (beta = 0.40, 95% CI, 0.03-0.76); higher PDS overall and gonadal scores were associated with higher pain intensity ( P s < 0.05). Associations with hormones were seen in boys only, with each 10-fold higher testosterone levels associated with a 40% lower risk of pain incidence (95% CI, -55% to -22%) and 1.30-point lower (95% CI, -2.12 to -0.48) pain intensity, and higher DHEA levels were associated with lower pain intensity ( P = 0.020). Relationships between pubertal development and pain in peripubertal adolescents are sex specific and puberty measurement specific and warrant further investigation.
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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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Fibromyalgia has been characterized by augmented cross-network functional communication between the brain's sensorimotor, default mode, and attentional (salience/ventral and dorsal) networks. However, the underlying mechanisms of these aberrant communication patterns are unknown. In this study, we sought to understand large-scale topographic patterns at instantaneous timepoints, known as co-activation patterns (CAPs). ⋯ Using proton magnetic resonance spectroscopy, we found that greater basal excitatory over inhibitory neurotransmitter levels within the anterior insula orchestrated higher cross-network connectivity between the anterior insula and the default mode network through lower occurrence of a CAP encompassing the attentional networks during sustained pain. Moreover, we found that hyperalgesia in fibromyalgia was mediated through increased occurrence of a CAP encompassing the sensorimotor network during sustained pain. In conclusion, this study elucidates the role of momentary large-scale topographic brain patterns in shaping noxious information in patients with fibromyalgia, while laying the groundwork for using precise spatiotemporal dynamics of the brain for the potential development of therapeutics.
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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.