Pain
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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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Cold allodynia is a common complaint of patients suffering from neuropathic pain initiated by peripheral nerve injury. However, the mechanisms that drive neuropathic cold pain remain elusive. In this study, we show that the interleukin (IL)-33/ST2 signaling in the dorsal root ganglion (DRG) is a critical contributor to neuropathic cold pain by interacting with the cold sensor transient receptor potential melastatin 8 (TRPM8). ⋯ Co-immunoprecipitation assays further reveal that ST2 interacts with TRPM8 in DRG neurons. Importantly, rIL-33-induced cold allodynia is abolished by pharmacological inhibition of TRPM8 and genetic ablation of the TRPM8-expressing neurons. Thus, our findings suggest that the IL-33/ST2 signaling mediates neuropathic cold pain through downstream cold-sensitive TRPM8 channels, thereby identifying a potential analgesic target for the treatment of neuropathic cold pain.
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Menopausal and postmenopausal women, characterized by a significant reduction in ovarian hormones, have a high prevalence of chronic pain with great pain intensity. However, the underlying mechanism of hyperalgesia induced by ovarian hormone withdrawal remains poorly understood. ⋯ Moreover, activation of the DRNGABA neurons projecting to the lateral parabrachial nucleus was critical for alleviating hyperalgesia in OVX mice. These findings show the essential role of DRNGABA neurons and their modulation by estrogen in regulating hyperalgesia induced by ovarian hormone withdrawal, providing therapeutic basis for the treatment of chronic pain in physiological or surgical menopausal women.
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Spinal cord injury leads to hyperexcitability and dysfunction in spinal sensory processing. As hyperexcitable circuits can become epileptiform, we explored whether such activity emerges in a thoracic spinal cord injury (SCI) contusion model of neuropathic pain. Recordings from spinal sensory axons in multiple below-lesion segmental dorsal roots demonstrated that SCI facilitated the emergence of spontaneous ectopic burst spiking in afferent axons, which were correlated across multiple adjacent dorsal roots. ⋯ We conclude that spinal cord injury promotes the emergence of epileptiform activity in spinal sensory networks that promote profound corruption of sensory signaling. This includes hyperexcitability and bursting by ectopic spiking in afferent axons that propagate bidirectionally by reentrant central and peripheral projections as well as sensory circuit hypoexcitability during the burst refractory period. More broadly, the work links circuit hyperexcitability to epileptiform circuit emergence, further strengthening it as a conceptual basis to understand features of sensory dysfunction and neuropathic pain.
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This is the first study to empirically determine the potential for data-driven personalization in the context of chronic primary pain (CPP). Effect sizes of psychological treatments for individuals with CPP are small to moderate on average. Aiming for better treatment outcomes for the individual patient, the call to personalize CPP treatment increased over time. ⋯ However, this result warrants careful consideration. Further research is needed to shed light on the heterogeneity of psychological treatment studies and thus to uncover the full potential of data-driven personalized psychotherapy for patients with CPP. A Bayesian variance ratio meta-regression indicates empirical evidence that data-driven personalized psychotherapy for patients with chronic primary pain could increase effects of cognitive behavioral therapy.