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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Pharmacological ablation of rostral ventromedial medulla (RVM) mu opioid receptor-expressing cells before peripheral nerve injury prevents the development of neuropathic pain. However, whether these neurons are required for the expression of established neuropathic pain is not known. Male Oprm1Cre heterozygous (MOR Cre ) or wild-type (MOR WT ) mice received AAV8-hSyn-DIO-hM4D(Gi)-mCherry in the RVM. ⋯ Sustained CNO in drinking water before PSNL prevented expression of chronic pain without affecting acute surgical pain; however, relief of chronic pain required sustained CNO treatment. Thus, in male mice, activity of spinally projecting RVM-MOR cells is required (1) for expression and manifestation of both sensory and affective dimensions of established neuropathic pain and (2) to promote descending facilitation that overcomes apparently intact descending inhibition to maintain chronic pain. Enhanced descending facilitation likely regulates the output signal from the spinal cord to the brain to shape the pain experience and may provide a mechanism for nonopioid management of pain.
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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.