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The rostral ventromedial medulla (RVM) is a bulbospinal nuclei in the descending pain modulation system, and directly affects spinal nociceptive transmission through pronociceptive ON cells and antinociceptive OFF cells in this area. The functional status of ON and OFF neurons play a pivotal role in pain chronification. As distinct pain modulative information converges in the RVM and affects ON and OFF cell excitability, neural circuits and transmitters correlated to RVM need to be defined for an in-depth understanding of central-mediated pain sensitivity. In this review, neural circuits including the role of the periaqueductal gray, locus coeruleus, parabrachial complex, hypothalamus, amygdala input to the RVM, and RVM output to the spinal dorsal horn are discussed. Meanwhile, the role of neurotransmitters is concluded, including serotonin, opioids, amino acids, cannabinoids, TRPV1, substance P and cholecystokinin, and their dynamic impact on both ON and OFF cell activities in modulating pain transmission. Via clarifying potential specific receptors of ON and OFF cells, more targeted therapies can be raised to generate pain relief for patients who suffer from chronic pain.

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X221113897 for Neuronal Serpina3n is an endogenous protector against blood brain barrier damage following cerebral ischemic stroke by Fengshi Li, Yueman Zhang, Ruqi Li, Yan Li, Shenghao Ding, Jianpo Zhou, Tianchen Huang, Chen Chen, Bingwei Lu, Weifeng Yu, Johannes Boltze, Peiying Li, Jieqing Wan in Journal of Cerebral Blood Flow & Metabolism

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X221113897 for Neuronal Serpina3n is an endogenous protector against blood brain barrier damage following cerebral ischemic stroke by Fengshi Li, Yueman Zhang, Ruqi Li, Yan Li, Shenghao Ding, Jianpo Zhou, Tianchen Huang, Chen Chen, Bingwei Lu, Weifeng Yu, Johannes Boltze, Peiying Li, Jieqing Wan in Journal of Cerebral Blood Flow & Metabolism

Supplemental material, sj-docx-1-jic-10.1177_08850666211037326 for Predictive Value of Eosinophil Count on COVID-19 Disease Progression and Outcomes, a Retrospective Study of Leishenshan Hospital in Wuhan, China by Wei Xuan, Xuliang Jiang, Lili Huang, Shuting Pan, Caiyang Chen, Xiao Zhang, Hui Zhu, Song Zhang, Weifeng Yu, Zhiyong Peng and Diansan Su in Journal of Intensive Care Medicine

Additional file 3:. A supplementary table with all items from the WHO trial registry data set.

Additional file 2:. Qo-R 40 scale.

Additional file 4:. Informed consent form.

Neuropathic pain (NP) remains a significant clinical problem worldwide. Toll-like rec e ptor 4 (TLR4) expressed on microglia in the spinal cord exert great influence on NP induced hyperalgesia. Impaired γ-aminobutyric acid (GABAergic) neuron activities in the spinal cordare also confirmed to be associated with NP progression. However, the role of TLR4 inducedmicroglial activation on impaired spinal GABAergic neuron activities inneuropathic painconditions remains unclear. Mechanical thr esholds were measured after intrathecal injectionof TLR4 inhibitor (TAK-242) or GABAA receptor agonist (muscimol) in male C57 mice. Microglialactivation, glutamic acid decarboxylase 65 (GAD65), as well as GABA concentrations incerebrospinal fluid (CSF) were further analyzed. Spontaneous inhibitory postsynaptic current(sIPSC) of GABAergic neurons were recorded using electrophysiological test. TLR4 expressionlevel was measured after chronic constriction injury (CCI) surgery and after intrathecaladministration of a TLR4 agonist (lipopolysaccharide, LPS) in naive mice.CCI surgery and TLR4agonist LPS treatment both induced hyperalgesia, while TLR4 inhibitor TAK-242 or GABAAreceptor agonist muscimol increased the mechanical thresholds in both CCI surgery andLPS-treated mice. Furthermore, decreased GAD65 fluorescence, GABA concentrations in CSFand sIPSC in CCI and LPS mice were a lleviated by TAK-242. Moreover, TAK-242 and microg lia activa tion inhibitor (minocycline) suppressed the enhanced microglial activation in CCI surgeryand LPS-treated mice, and GAD65 fluorescence and GABA concentrations were increased byminocycline intervention. Additionally, TLR4 expression levels were up-regulated followingCCI surgery and intrathecal administration of LPS. TLR4 suppresses spinal GABAergic neuronactivities viamicroglial activation.

A number of case reports now indicate that rocuronium can induce a number of serious side effects. We hypothesized that these side effects might be mediated by the inhibition of nicotinic acetylcholine receptors (nAChRs) at superior cervical ganglion (SCG) neurons. Conventional patch clamp recordings were used to study the effects of rocuronium on nAChR currents from enzymatically dissociated rat SCG neurons. We found that ACh induced a peak transient inward current in rat SCG neurons. Additionally, rocuronium suppressed the peak ACh-evoked currents in rat SCG neurons in a concentration-dependent and competitive manner, and it increased the extent of desensitization of nAChRs. The inhibitory rate of rocuronium on nAChR currents did not change significantly at membrane potentials between -70 and -20 mV, suggesting that this inhibition was voltage independent. Lastly, rocuronium preapplication enhanced its inhibitory effect, indicating that this drug might prefer to act on the closed state of nAChR channels. In conclusion, rocuronium, at clinically relevant concentrations, directly inhibits nAChRs at the SCG by interacting with both opened and closed states. This inhibition is competitive, dose dependent, and voltage independent. Blockade of synaptic transmission in the sympathetic ganglia by rocuronium might have potentially inhibitory effects on the cardiovascular system.