Articles: hyperalgesia.
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Hyperalgesic priming is a model system that has been widely used to understand plasticity in painful stimulus-detecting sensory neurons, called nociceptors. A key feature of this model system is that following priming, stimuli that do not normally cause hyperalgesia now readily provoke this state. We hypothesized that hyperalgesic priming occurs because of reorganization of translation of mRNA in nociceptors. ⋯ A GPR88 agonist injection into the paw had no effect in naive mice but caused mechanical hypersensitivity and grimacing responses in female primed mice. Systemic Meteorin treatment in primed mice completely reversed established hyperalgesic priming mechanical hypersensitivity and grimacing responses to prostaglandin E2 in female mice. Our work demonstrates that altered nociceptor translatomes are causative in producing hyperalgesic priming in multiple models in female mice.
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Review
Multifaceted roles of DLG3/SAP102 in neurophysiology, neurological disorders and tumorigenesis.
DLG3, also known as Synapse-associated protein 102 (SAP102), is essential for the organization and plasticity of excitatory synapses within the central nervous system (CNS). It plays a critical role in clustering and moving key components necessary for learning and memory processes. Mutations in the DLG3 gene, which result in truncated SAP102 proteins, have been associated with a range of neurological disorders, including X-linked intellectual disability (XLID), autism spectrum disorders (ASD), and schizophrenia, all of which can disrupt synaptic structure and cognitive functions. ⋯ Moreover, SAP102 has been demonstrated to regulate tumor-induced bone pain through activating NMDA receptors. These findings highlight SAP102 as a promising therapeutic target for both neurological disorders and cancer. Therefore, further investigation into the regulatory roles of SAP102 in neural development and disease may lead to novel therapeutic approaches for treating synaptic disorders and managing cancer progression.
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Placebo hypoalgesia and nocebo hyperalgesia, which exemplify the impact of expectations on pain, have recently been conceptualised as Bayesian inferential processes, yet empirical evidence remains limited. Here, we explore whether these phenomena can be unified within the same Bayesian framework by testing the predictive role of expectations and their level of precision (ie, expectation confidence) on pain, with both predictors measured at the metacognitive level. Sixty healthy volunteers underwent a pain test (ie, 8 noxious electrical stimuli) before (Baseline) and after (T0, T1, T2) receiving a sham treatment associated with hypoalgesic (placebo), hyperalgesic (nocebo), or neutral (control) verbal suggestions, depending on group allocation. ⋯ This suggests that both placebo and nocebo responses are well described from a Bayesian perspective. A main effect of time for SCR was observed, suggesting habituation to painful stimuli. Our data provide evidence indicating that both placebo hypoalgesia and nocebo hyperalgesia can be unified within the same Bayesian framework in which not only expectations but also their level of precision, both measured at the metacognitive level, are key determinants of the pain inferential process.
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Quantitative sensory testing (QST) is a set of methods for quantifying somatosensory functioning. Limitations of laboratory-based QST (LQST) include high cost, complexity in training, lack of portability, and time requirements for testing. Translating QST to a home setting could facilitate future research and clinical care. ⋯ The participants rated the HQST protocol as highly acceptable and safe but can be improved in future implementations. Home QST was able to detect hypoesthesia to vibration after lidocaine cream application ( P = 0.024, d = 0.502) and could detect hypoalgesia and hyperalgesia to pressure and heat pain sensitivity tests after application of lidocaine and capsaicin creams, respectively ( P -value range = <0.001-0.036, d -value range = 0.563-0.901). Despite limitations, HQST tool-kits may become a cost-effective, convenient, and scalable approach for improving sensory profiling in clinical care and clinical research.
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Randomized Controlled Trial
Independent effects of transcranial direct current stimulation and social influence on pain.
Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulatory technique with the potential to provide pain relief. However, tDCS effects on pain are variable across existing studies, possibly related to differences in stimulation protocols and expectancy effects. We investigated the independent and joint effects of contralateral motor cortex tDCS (anodal vs cathodal) and socially induced expectations (analgesia vs hyperalgesia) about tDCS on thermal pain. ⋯ The observed additive effects provide novel evidence that tDCS and socially induced expectations operate through independent processes. They extend clinical tDCS studies by showing tDCS effects on controlled nociceptive pain independent of expectancy effects. In addition, they show that social suggestions about neurostimulation effects can elicit potent placebo effects.