Accepted

This study aimed to investigate the potential contribution of quantitative measurements of dural venous sinuses to the diagnosis of idiopathic intracranial hypertension (IIH) and the relationship between IIH and dural venous sinus dimensions on 3D post-gadolinium T1-weighted magnetic resonance (MR) images.

Vestibular migraine (VM) is one of the most common causes of episodic central vestibular disorders; it is worth investigating whether VM belongs to the migraine subtype or is a separate disorder. The study is aimed at investigating resting-state functional brain activity alterations in patients with definite VM (dVM).

Rheumatoid arthritis (RA) is well-known as a kind of autoimmune disease, which brings unbearable pain to the patients by multiple organ complications besides arthritis. To date, RA can be hardly cured, but early diagnosis and standard treatment can relieve symptoms and pain. Therefore, an effective tool to assist the early diagnosis of RA deserves considerable attention. On account of the overexpressed ONOO during the early stage of RA, a near-infrared (NIR) receptor, Lyso-Cy, is proposed in this work by linker chemistry to expand the conjugated rhodamine framework by cyanine groups. Contributed by the pH-sensitive spiral ring in rhodamine, receptor Lyso-Cy has been found to be workable in lysosomes specifically, which was confirmed by the pH-dependent spectra with a narrow responding region and a well-calculated p value of 5.81. We presented an excellent ratiometric sensing protocol for ONOO in an acidic environment, which was also available for targeting ONOO in lysosomes selectively. This innovative dual-targeting responsive design is expected to be promising for assisting RA diagnosis at an early stage with respect to the joint inflammatory model established in this work at the organism level.

The voltage-gated sodium Na1.7 channel plays a key role as a mediator of action potential propagation in C-fiber nociceptors and is an established molecular target for pain therapy. ProTx-II is a potent and moderately selective peptide toxin from tarantula venom that inhibits human Na1.7 activation. Here we used available structural and experimental data to guide Rosetta design of potent and selective ProTx-II-based peptide inhibitors of human Na1.7 channels. Functional testing of designed peptides using electrophysiology identified the PTx2-3127 and PTx2-3258 peptides with ICs of 7 nM and 4 nM for hNa1.7 and more than 1,000-fold selectivity over human Na1.1, Na1.3, Na1.4, Na1.5, Na1.8, and Na1.9 channels. PTx2-3127 inhibits Na1.7 currents in mouse and human sensory neurons and shows efficacy in rat models of chronic and thermal pain when administered intrathecally. Rationally-designed peptide inhibitors of human Na1.7 channels have transformative potential to define a new class of biologics to treat pain.

Conventional recording of F-waves from the vastus lateralis muscle causes severe pain in some subjects. Thus, we aimed to investigate the effects of the stimulation frequency on pain and F-wave parameters when recording F-waves from this muscle and to develop a method for recording F-waves from the vastus lateralis muscle that causes minimal pain.

Chemotherapy-induced peripheral neuropathy is one of the most frequent dose-limiting side effects, observed in patients receiving antineoplastic agents, persisting for up to two years after completing treatment, greatly affecting both the course of chemotherapy and patients' quality of life. Approximately 20 to 85% of patients treated with neurotoxic chemotherapy will develop peripheral neuropathy and there is considerable variability in its severity among patients. The main symptoms are numbness, paresthesia, and burning pain in a "glove and stocking" distribution. The prevalence of chemotherapy-induced peripheral neuropathy will likely increase as cancer survival rates continue to improve. Currently, there are only a few therapeutic options available for the prevention or successful therapy because the mechanisms of chemotherapy-induced peripheral neuropathy remain unclear. A better understanding of the risk factors and underlying mechanisms of chemotherapy-induced peripheral neuropathy is needed to develop effective preventive and therapeutic strategies.

Irritable bowel syndrome and bladder pain syndrome often overlap and are both characterized by visceral hypersensitivity. Since pelvic organs share common sensory pathways, it is likely that those syndromes involve a cross-sensitization of the bladder and the colon. The precise pathophysiology remains poorly understood.

Pain is an unpleasant subjective experience that is usually modified by complex multidimensional neuropsychological processes. Increasing numbers of neuroimaging studies in humans have characterized the hierarchical brain areas forming a pain matrix, which is involved in the different dimensions of pain components. Although mechanistic investigations have been performed extensively in rodents, the homologous brain regions involved in the multidimensional pain components have not been fully understood in the rodent brain. Herein, we successfully identified several brain regions activated in response to mechanical allodynia in neuropathic pain rat models using an alternative neuroimaging method based on 2-deoxy-2-[F]fluoro-d-glucose positron emission tomography (FDG PET) scanning. Regions such as the medial prefrontal cortex, primary somatosensory cortex hindlimb region, and the centrolateral thalamic nucleus were identified. Moreover, brain activity in these regions was positively correlated with mechanical allodynia-related behavioral changes. These results suggest that FDG PET imaging in neuropathic pain model rats enables the evaluation of regional brain activity encoding the multidimensional pain aspect. It could thus be a fascinating tool to bridge the gap between preclinical and clinical investigations.