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Migraine is a common brain disorder that predominantly affects women. Migraine pain seems mediated by the activation of mechanosensitive channels in meningeal afferents. Given the role of transient receptor potential melastatin 3 (TRPM3) channels in mechanical activation, as well as hormonal regulation, these channels may play a role in the sex difference in migraine. Therefore, we investigated whether nociceptive firing induced by TRPM3 channel agonists in meningeal afferents was different between male and female mice. In addition, we assessed the relative contribution of mechanosensitive TRPM3 channels and that of mechanosensitive Piezo1 channels and transient receptor potential vanilloid 1 (TRPV1) channels to nociceptive firing relevant to migraine in both sexes.
Learn More >Opioid use disorder (OUD) and chronic pain frequently co-occur. Little is known about changes in pain during buprenorphine/naloxone (BUP/NX) maintenance and whether outcomes vary by pain levels. The present study examined changes in pain intensity and pain interference over 12 weeks of BUP/NX maintenance among participants with OUD and chronic pain ( = 194). Differences in outcomes were assessed during BUP/NX maintenance (Week 12) and 2 months following a BUP/NX taper (Week 24).
Learn More >Opioid-induced hyperalgesia (OIH) is a problem associated with prolonged use of opioids in chronic pain management, and its effective treatment has been hampered by lack of mechanistic evidence. Oligodendrocytes have recently been linked with several pain-related diseases; however, little is known its role in OIH. The prelimbic medial prefrontal cortex (PL-mPFC) has emerged as a significant center of pain regulation, and is rich in oligodendrocytes. Herein we explored the effect of oligodendrocyte apoptosis of PL-mPFC on OIH. Using a fentanyl-induced rat model of OIH and proteomics analysis of the PL-mPFC, we observed a downregulation in five types of myelin-related proteins originating from oligodendrocytes; this was further verified by western blotting. Meanwhile, cleaved-caspase 3 (an apoptosis marker) was increased, whereas the oligodendrocyte precursor cell (OPC) marker NG2 remained unchanged. These results suggest that downregulated myelin-related proteins may be associated with oligodendrocyte apoptosis rather than a reduction in their generating source, and immunohistochemistry confirmed this hypothesis. Behaviorally, prophylactic blockade of oligodendrocyte apoptosis by microinjection of z-DEVD-fmk into the PL-mPFC prevented fentanyl-induced mechanical and thermal hyperalgesia, but downregulated myelin basic protein (mbp) gradually recovered in 12 h. We suggest that OIH may be primed in part via oligodendrocyte apoptosis in the PL-mPFC. PERSPECTIVE: : In this study we showed that oligodendrocyte apoptosis in the PL-mPFC is a key trigger for fentanyl-induced hyperalgesia. Targeting oligodendrocyte apoptosis in the PL-mPFC may prevented hyperalgesia priming induced by fentanyl.
Learn More >To examine how often urologic chronic pelvic pain syndrome (UCPPS) patients progressed from Pelvic Pain Only at baseline to Widespread Pain, or vice versa, during one-year longitudinal follow-up.
Learn More >Inactivation of sensory neurons expressing transient receptor potential vanilloid 1 (TRPV1) enhances breast cancer metastasis. Sensory neurons have profound effects on immune response to a wide range of diseases including cancer. Hence, activation of sensory nerves using feasible approaches such as specific TRPV1 agonists may inhibit breast cancer metastasis through neuroimmune pathways. TRPV1 agonists are considered for the treatment of pain and inflammatory diseases.
Learn More >Chronic pain is debilitating and profoundly affects health-related quality of life. Spinal cord stimulation (SCS) is a well-established therapy for chronic pain; however, SCS has been limited by the inability to directly measure the elicited neural response, precluding confirmation of neural activation and continuous therapy. A novel SCS system measures the evoked compound action potentials (ECAPs) to produce a real-time physiological closed-loop control system.
Learn More >Sleep deprivation has been shown to increase pain intensity and decrease pain thresholds in healthy subjects. In chronic pain patients, sleep impairment often worsens the perceived pain intensity. This increased pain perception is the result of altered nociceptive processing. We recently developed a method to quantify and monitor altered nociceptive processing by simultaneous tracking of psychophysical detection thresholds and recording of evoked cortical potentials during intra-epidermal electric stimulation. In this study, we assessed the sensitivity of nociceptive detection thresholds and evoked potentials to altered nociceptive processing after sleep deprivation in an exploratory study with 24 healthy male and 24 healthy female subjects. In each subject, we tracked nociceptive detection thresholds and recorded central evoked potentials in response to 180 single- and 180 double-pulse intra-epidermal electric stimuli. Results showed that the detection thresholds for single- and double-pulse stimuli and the average central evoked potential for single-pulse stimuli were significantly decreased after sleep deprivation. When analyzed separated by sex, these effects were only significant in the male population. Multivariate analysis showed that the decrease of central evoked potential was associated with a decrease of task-related evoked activity. Measurement repetition led to a decrease of the detection threshold to double-pulse stimuli in the mixed and the female population, but did not significantly affect any other outcome measures. These results suggest that simultaneous tracking of psychophysical detection thresholds and evoked potentials is a useful method to observe altered nociceptive processing after sleep deprivation, but is also sensitive to sex differences and measurement repetition.
Learn More >The Pain Vigilance and Awareness Questionnaire (PVAQ) is a questionnaire for non-clinical and clinical cases of patients, such as those suffering from chronic pain. Moreover, it is used for evaluation of two aspects of habitual attention to pain: attention to pain and attention to changes in pain. As the PVAQ assesses two different aspects of attention function, different neural basis may present. However, it remains unclear which brain regions are involved. Here, we performed voxel-based morphometry (VBM) in 30 healthy participants to determine the regional morphology associated with the two attention states. Multiple regression analysis was conducted between each score and the regional grey matter (GM) volume, which revealed that a decreased GM volume in the left anterior insular cortex (AIC) was associated with a higher attention to pain score. In contrast, no brain region was correlated with the attention to changes in pain score. Our VBM results demonstrate that attention to pain scores assessed by PVAQ are associated with morphological features of the left AIC. Moreover, they may contribute to the elucidation of the complex psychological and neurophysiological characteristics of patients with chronic pain.
Learn More >Pain can be ignited by noxious chemical (e.g., acid), mechanical (e.g., pressure), and thermal (e.g., heat) stimuli and generated by the activation of sensory neurons and their axonal terminals called nociceptors in the periphery. Nociceptive information transmitted from the periphery is projected to the central nervous system (thalamus, somatosensory cortex, insular, anterior cingulate cortex, amygdala, periaqueductal grey, prefrontal cortex, etc.) to generate a unified experience of pain. Local field potential (LFP) recording is one of the neurophysiological tools to investigate the combined neuronal activity, ranging from several hundred micrometers to a few millimeters (radius), located around the embedded electrode. The advantage of recording LFP is that it provides stable simultaneous activities in various brain regions in response to external stimuli. In this study, differential LFP activities from the contralateral anterior cingulate cortex (ACC), ventral tegmental area (VTA), and bilateral amygdala in response to peripheral noxious formalin injection were recorded in anesthetized male rats. The results indicated increased power of delta, theta, alpha, beta, and gamma bands in the ACC and amygdala but no change of gamma-band in the right amygdala. Within the VTA, intensities of the delta, theta, and beta bands were only enhanced significantly after formalin injection. It was found that the connectivity (i.t. the coherence) among these brain regions reduced significantly under the formalin-induced nociception, which suggests a significant interruption within the brain. With further study, it will sort out the key combination of structures that will serve as the signature for pain state.
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