Pain
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Human experimental studies have shown that levcromakalim, an ATP-sensitive potassium (K ATP ) channel opener, induces migraine attacks in people with migraine but not in healthy volunteers. However, the exact site of action for K ATP channels in migraine pathophysiology remains unclear. This study investigates the role of these channels in the meninges in eliciting behavioral hypersensitivity responses in mice. ⋯ Finally, dural coinjection of glibenclamide inhibited periorbital hypersensitivity induced by CGRP or prolactin in female mice. These studies demonstrate that the meninges can be one site of action for the migraine-triggering effects of K ATP channel openers. They also show that NO donors, CGRP, and prolactin can produce behavioral hypersensitivity through opening of K ATP channels in the meninges.
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Chronic pain is a pervasive and debilitating condition with increasing implications for public health, affecting millions of individuals worldwide. Despite its high prevalence, the underlying neural mechanisms and pathophysiology remain only partly understood. Since its introduction 35 years ago, brain diffusion magnetic resonance imaging (MRI) has emerged as a powerful tool to investigate changes in white matter microstructure and connectivity associated with chronic pain. ⋯ We conclude by highlighting emerging approaches and prospective avenues in the field that may provide new insights into the pathophysiology of chronic pain and potential new therapeutic targets. Because of the limited current body of research and unidentified targeted therapeutic strategies, we are forced to conclude that further research is required. However, we believe that brain diffusion MRI presents a promising opportunity for enhancing our understanding of chronic pain and improving clinical outcomes.
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For trigeminal neuralgia (TN), a major role of imaging is to identify the causes, but recent studies demonstrated structural and microstructural changes in the affected nerve. Moreover, an increasing number of studies have reported central nervous system involvement in TN. In this systematic review, recent quantitative magnetic resonance imaging (MRI) studies of the trigeminal nerve and the brain in patients with TN were compiled, organized, and discussed, particularly emphasizing the possible background mechanisms and the interpretation of the results. ⋯ Studies of the affected nerve demonstrated evidence of demyelination and axonal damage, compatible with pathological findings, and have shown its potential value as a tool to assess treatment outcomes. Quantitative MRI has also revealed the possibility of dynamic microstructural, structural, and functional neuronal plasticity of the brain. Further studies are needed to understand these complex mechanisms of neuronal plasticity and to achieve a consensus on the clinical use of quantitative MRI in TN.
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Spinal cord stimulation (SCS) is an effective modality for pain treatment, yet its underlying mechanisms remain elusive. Neurokinin 1 receptor-positive (NK1R + ) neurons in spinal lamina I play a pivotal role in pain transmission. To enhance our mechanistic understanding of SCS-induced analgesia, we investigated how different SCS paradigms modulate the activation of NK1R + neurons, by developing NK1R-Cre;GCaMP6s transgenic mice and using in vivo calcium imaging of superficial NK1R + neurons under anesthesia (1.5% isoflurane). ⋯ However, at low intensity (20% MoT), the 30-minute 900-Hz SCS only induced persistent neuronal inhibition in naïve mice, but not in SNI-t mice. In conclusion, both 10-minute high-intensity SCS and 30-minute SCS at moderate intensity inhibit the activation of superficial NK1R + neurons, potentially attenuating spinal nociceptive transmission. Furthermore, in vivo calcium imaging of NK1R + neurons provides a new approach for exploring the spinal neuronal mechanisms of pain inhibition by neuromodulation pain therapies.
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Using cross-sectional data from the United States, England, China, and India, we examined the relationship between education and frequent pain, alongside the modification role of gender in this relationship. We further examined patterns of 3 pain dimensions among participants who reported frequent pain, including pain severity, interference with daily activities, and medication use (these pain dimension questions were not administered in all countries). Our analytical sample included 92,204 participants aged 50 years and above. ⋯ In the United States, these associations were stronger among women. Our findings highlight the prevalent pain among middle-aged and older adults in these 4 countries and emphasize the potentially protective role of higher education on frequent pain, with nuanced gender differences across different settings. This underscores the need for tailored strategies considering educational and gender differences to improve pain management and awareness.