Articles: hyperalgesia.
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Pain perception is closely tied to the brain's anticipatory processes, particularly involving the suppression of sensorimotor α-oscillations, which reflect the system's readiness for incoming pain. Higher sensorimotor α-oscillation levels are correlated with lower pain sensitivity. Alpha transcranial alternating current stimulation (α-tACS) can enhance these oscillations, potentially reducing pain perception, with effects that may be sustained and influenced by the certainty of pain expectations. ⋯ In anticipatory brain oscillations, real α-tACS enhanced somatosensory α1-oscillations and increased midfrontal θ-oscillations in conditions of certainty, with θ-oscillation modulation showing sustained effects. Mediation analysis revealed that α-tACS reduced pain reactivity by enhancing somatosensory α1-oscillations but increased pain reactivity through the enhancement of midfrontal θ-oscillations, with the latter effect being more pronounced. These findings suggest that while α-tACS may provide pain relief through somatosensory α-oscillation augmentation, its stronger and longer-lasting impact on midfrontal θ-oscillations could lead to hyperalgesia, particularly in the context of certain pain expectations.
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Treating bone cancer pain (BCP) continues to be a clinical challenge, and the underlying mechanisms of BCP remain elusive. This study reports that Wnt5a/Ryk signaling in the dorsal root ganglion neurons is critical to the development of BCP. Tibia bone cavity tumor cell implantation produces spontaneous and evoked behaviorally expressed pain as well as ectopic sprouting and activity of Wnt5a/Ryk signaling in the neural soma and peripheral terminals and the tumor-affected bone tissues. ⋯ Blocking Ryk receptor activation suppresses Wnt5a-induced mechanical allodynia and thermal hyperalgesia. Wnt5a facilitation of transient receptors potential vanilloid type-1 sensitization is blocked by inhibiting c-Jun N-terminal kinase activation. These findings indicate a critical peripheral mechanism of Wnt5a/Ryk signaling underlying the pathogenesis of BCP and suggest that targeting Wnt5a/Ryk in the primary sensory neurons and the tumor-invasive area may be an effective approach for the prevention and treatment of BCP.
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Randomized Controlled Trial
The downside to choice: instrumental control increases conditioned nocebo hyperalgesia.
Nocebo hyperalgesia is a pervasive problem in which the treatment context triggers negative expectations that exacerbate pain. Thus, developing ethical strategies to mitigate nocebo hyperalgesia is crucial. Emerging research suggests that choice has the capacity to reduce nocebo side effects, but choice effects on nocebo hyperalgesia have not been explored. ⋯ The positive choice information failed to attenuate the effect of choice on nocebo hyperalgesia. The current results suggest that, rather than decreasing nocebo hyperalgesia, treatment choice may exacerbate pain outcomes when a painful procedure is repeatedly administered. As such, using choice as a strategy to mitigate nocebo outcomes should be treated with caution.
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Spinal cord injury (SCI) presents a major global health challenge, with rising incidence rates and substantial disability. Although progress has been made in understanding SCI's pathophysiology and early management, there is still a lack of effective treatments to mitigate long-term consequences. This study investigates the potential of sovateltide, a selective endothelin B receptor agonist, in improving clinical outcomes in an acute SCI rat model. ⋯ This study suggests that sovateltide may offer neuroprotective effects, enhancing neurogenesis and angiogenesis. Furthermore, it may possess anti-inflammatory and antinociceptive properties. Future clinical trials are needed to validate these findings, but sovateltide shows promise as a potential therapeutic strategy to improve functional outcomes in SCI. Sovateltide, an endothelin B receptor agonist, exhibits neuroprotective properties, enhancing motor recovery and ameliorating hyperalgesia in a rat SCI model. These findings could pave the way for innovative pharmacological interventions for SCI in clinical settings.
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Hand-holding reduces experimentally induced acute pain and buffers against the development of mechanical secondary hypersensitivity, an indirect proxy of central sensitization. Here, we tested if verbal support from a stranger, a common occurrence in clinical contexts, exerts the same effects. In this preregistered study, 44 healthy female participants were assigned to an alone or support group whereby a supportive female stranger encouraged them through the painful procedure leading to secondary mechanical hypersensitivity. ⋯ PERSPECTIVE: Verbal support by a stranger during a painful procedure leading to secondary mechanical hypersensitivity attenuated the development of some measures of mechanical hypersensitivity and associated neural responses in healthy female participants. No evidence was found for the role of stress. DATA AVAILABILITY: The authors will make all data available upon request.