Pain
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Wind-up is a frequency-dependent increase in the response of spinal cord neurons, which is believed to underlie temporal summation of nociceptive input. However, whether spinoparabrachial neurons, which likely contribute to the affective component of pain, undergo wind-up was unknown. ⋯ We show that one-fifth of lamina I spinoparabrachial neurons undergo wind-up, and provide evidence that wind-up in these cells is mediated in part by a network of spinal excitatory interneurons that show reverberating activity. These findings provide insight into a polysynaptic circuit of sensory augmentation that may contribute to the wind-up of pain's unpleasantness.
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Resilience is a psychological trait that strongly predicts chronic pain-related health outcomes. The neural correlates of both pain and trait resilience are critical to understand the brain-behaviour relationship in chronic pain; yet, neural correlates of resilience in chronic pain states are unknown. However, measures of pain perception and a wide range of psychological health measures have been linked to function of the default mode network (DMN). ⋯ Finally, there was an interaction between within-DMN FC and clinical pain report in patients: In patients reporting greater pain, the relationship between within-DMN connectivity and resilience was atypical. Thus, our findings reveal different neural representations of resilience and pain. The way in which these behavioural measures interact provides insight into understanding the neural correlates of chronic pain.
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Interleukin-6 trans-signaling and pathological low back pain in patients with Paget disease of bone.
The interleukin (IL)-6 biological system plays a key role in the pathogenesis of Paget disease (PD) of bone and pathological bone pain. Bone pain, particularly in the lower back region, is the most frequent symptom in patients with PD. This case-control study aimed to evaluate the relationship between the IL-6 system and low back pain (LBP) in patients with PD. ⋯ Paget disease remission, 6 months after treatment, is associated with LBP improvement. This phenomenon is associated with reduced sIL-6R levels and increased sgp130 levels in patients with PD with LBP at the baseline. Considering the biological properties of IL-6, sIL-6R, and sgp130, the results of the study suggest that the perception of LBP in patients with PD could be linked to an enhanced transmission of IL-6 signal in the specialized neural system activated by nociceptors.
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Approximately one-third of individuals with sickle cell disease (SCD) develop chronic pain. This debilitating pain is inadequately treated because the underlying mechanisms driving the pain are poorly understood. In addition to persistent pain, patients with SCD are also in a tonically proinflammatory state. ⋯ Inhibition of chemokine receptor 2 (CCR2), but not CCR4, alleviated the behavioral mechanical and cold hypersensitivity in SCD. Furthermore, acute CCR2 blockade reversed both the behavioral and the in vitro responsiveness of sensory neurons to an agonist of TRPV1, a neuronal ion channel previously implicated in SCD pain. These results provide insight into the immune-mediated regulation of hypersensitivity in SCD and could inform future development of analgesics or therapeutic measures to prevent chronic pain.