Rejected

Neuropathic pain is the typical symptom of brachial plexus root avulsion (BPRA), and no effective therapy is currently available. Electroacupuncture (EA), as a complementary and alternative therapy, plays a critical role in the management of pain-associated diseases. In the present study, we aimed to reveal the peripheral immunological mechanism of EA in relieving the pain of BPRA through the IL-17-CD4 T lymphocyte-β-endorphin axis.

Anxiety is a common comorbidity associated with chronic pain, which results in chronic pain complexification and difficulty in treatment. Electroacupuncture (EA) is commonly used to treat chronic pain and anxiety. However, the underlying mechanisms of the EA effect are largely unknown. Here, we showed that a circuitry underlying chronic pain induces anxiety disorders, and EA can treat them by regulating such circuitry. Using chemogenetic methods, we found that chemogenetic activation of the rostral anterior cingulate cortex (rACC) glutamatergic output to the thalamus induced anxiety disorders in control rats. Then, chemogenetic inhibition of the rACC-thalamus circuitry reduced anxiety-like behavior produced by intraplantar injection of the complete Freund's adjuvant (CFA). In this study, we examined the effects of EA on a rat model of CFA-mediated anxiety-like behaviors and the related mechanisms. We found that chemogenetic activation of the rACC-thalamus circuitry effectively blocked the effects of EA on chronic pain-induced anxiety-like behaviors in CFA rats. These results demonstrate an underlying rACC-thalamus glutamatergic circuitry that regulates CFA-mediated anxiety-like behaviors. This study also provides a potential mechanistic explanation for EA treatment of anxiety caused by chronic pain.

Periodontal disease (PD) is an infectious-inflammatory oral disease that is highly prevalent among adolescence and adulthood and can lead to chronic orofacial pain and be associated with anxiety, stress and depression. This study aimed to identify anxiety-like behaviors in the ligature-induced murine preclinical model of PD in different phases of the disease (i.e., acute vs. chronic). Also, we investigated orofacial mechanical allodynia thresholds and superficial cortical plasticity along the orofacial motor cortex in both disease phases. To this aim, 25 male Wistar rats were randomly allocated in acute (14 days) or chronic (28 days) ligature-induced-PD groups and further divided into active-PD or sham-PD. Anxiety-like behavior was evaluated using the elevated plus maze, mechanical allodynia assessed using the von Frey filaments test and superficial motor cortex mapping was performed with electrical transdural stimulation. We observed increased anxiety-like behavior in active-PD animals in the acute phase, characterized by decreased number of entries into the open arm extremities [ = 2.42, = 0.04], and reduced time spent in the open arms [ = 3.56, = 0.01] and in the open arm extremities [ = 2.75, = 0.03]. There was also a reduction in the mechanical allodynia threshold in all active-PD animals [Acute: = 8.81, < 0.001; Chronic: = 60.0, < 0.001], that was positively correlated with anxiety-like behaviors in the acute group. No differences were observed in motor cortex mapping. Thus, our findings show the presence of anxiety-like behaviors in the acute phase of PD making this a suitable model to study the impact of anxiety in treatment response and treatment efficacy.

To explore the clinical characteristics of patients with recurrent trigeminal neuralgia (TN) and the experience of microvascular decompression (MVD) in the treatment of such patients. We retrospectively analyzed clinical data, imaging examination results, surgical methods, and treatment efficacies in 127 patients with recurrent typical TN from January 2005 to December 2014. The age of the recurrent group was higher than that of the non-recurrent group ( < 0.05). The duration of pain before the first MVD procedure was longer in the recurrent group than in the non-recurrent group ( < 0.05). Patients in the recurrent group were more likely to have compression of the trigeminal nerve by the vertebrobasilar artery (VBA) or multiple vessels than patients in the non-recurrent group ( < 0.05). A Kaplan-Meier curve showed a median pain-free survival of 12 months after the first MVD procedure. The severity of pain (preoperative visual analog scale [VAS] score) in patients with recurrence was lower than that in patients with first-onset TN ( < 0.05). Vessel compression, Teflon compression or granuloma and arachnoid adhesion were considered the main causes of recurrence. Postoperative Barrow Neurological Institute (BNI) scores in the redo MVD group were excellent ( = 2) for 69 patients (53.33%) and good ( = 3) for 46 patients (36.22%). The postoperative follow-up was 63-167 months (105.92 ± 25.66). During the follow-up, no recurrence was noted. All complications were cured or improved. Microvascular decompression (MVD) is an effective surgical method for the treatment of TN. For recurrent patients, reoperation can achieve good results.

Brachial plexus injuries (BPIs) are high-energy trauma that can result in serious functional problems in the affected upper extremities, and brachial plexus avulsion (BPA) could be considered the most severe type of them. The booming occurrence rate of BPA brings up devastating impact on patients' life. Complications of muscle atrophy, neuropathic pain, and denervation-associated psychological disorders are major challenges in the treatment of BPA. Animal models of BPA are good vehicles for this kind of research. Full understanding of the current in vivo BPA models, which could be classified into anterior approach avulsion, posterior approach avulsion, and closed approach avulsion groups, could help researchers select the appropriate type of models for their studies. Each group of the BPA model has its distinct merits and demerits. An ideal BPA model that can inherit the advantages and make up for the disadvantages is still required for further exploration.

Vanishing lung syndrome (VLS) is a rare condition characterized by giant emphysematous bullae. It is frequently misdiagnosed as pneumothorax. We describe a case of a 30-year-old male who presented with shortness of breath, reduced effort tolerance, and pleuritic chest pain for three months. He was initially diagnosed with bilateral pneumothorax based on clinical examination and chest radiograph findings. However, further imaging with a high resolution computed tomography (HRCT) of the thorax confirmed bilateral giant emphysematous bullae. Our patient subsequently underwent video-assisted thoracoscopic surgery (VATS) and bullectomy. In this report, we discuss the clinical presentations, radiological features, and the management of VLS. We also highlight the differentiating features of VLS from a pneumothorax.

Scorpion -analgesic-antitumor peptide (BmK AGAP) has been used to treat diseases like tetanus, tuberculosis, apoplexy, epilepsy, spasm, migraine headaches, rheumatic pain, and cancer in China. AGAP is a distinctive long-chain scorpion toxin with a molecular mass of 7142 Da and composed of 66 amino acids cross-linked by four disulfide bridges. Voltage-gated sodium channels (VGSCs) are present in excitable membranes and partakes in essential roles in action potentials generation as compared to the significant function of voltage-gated calcium channels (VGCCs). A total of nine genes (Na1.1-Na1.9) have been recognized to encode practical sodium channel isoforms. Na1.3, Na1.7, Na1.8, and Na1.9 have been recognized as potential targets for analgesics. Na1.8 and Na1.9 are associated with nociception initiated by inflammation signals in the neuronal pain pathway, while Na1.8 is fundamental for neuropathic pain at low temperatures. AGAP has a sturdy inhibitory influence on both viscera and soma pain. AGAP potentiates the effects of MAPK inhibitors on neuropathic as well as inflammation-associated pain. AGAP downregulates the secretion of phosphorylated p38, phosphorylated JNK, and phosphorylated ERK 1/2 . AGAP has an analgesic activity which may be an effective therapeutic agent for pain management because of its downregulation of PTX3 via NF-B and Wnt/beta-catenin signaling pathway. In cancers like colon cancer, breast cancer, lymphoma, and glioma, rAGAP was capable of blocking the proliferation. Thus, AGAP is a promising therapy for these tumors. Nevertheless, research is needed with other tumors.

There is an increasing demand to incorporate patient-reported outcome measures (PROMs) such as quality of life (QOL) in decision-making when selecting a chronic dialysis modality.

Narcolepsy is a sleep disorder marked by chronic, debilitating excessive daytime sleepiness and can be associated with cataplexy, sleep paralysis and sleep-related hallucinations. Pharmacological therapy for narcolepsy primarily aims to increase wakefulness and reduce cataplexy attacks. Pitolisant is a first-in-class agent utilizing histamine to improve wakefulness by acting as an antagonist/inverse agonist of the presynaptic histamine 3 receptor. This review summarizes the clinical efficacy, safety and tolerability of pitolisant in treating the symptoms of narcolepsy. Randomized and observational studies demonstrate pitolisant to be effective in treating both hypersomnolence and cataplexy while generally being well tolerated at prescribed doses. The most common adverse reactions include headache, insomnia and nausea.

The combination of naloxone hydrochloride (NH) and fentanyl citrate (FC) in patient-controlled analgesia (PCA) is examined to reduce the risk of opioid-induced nausea and vomiting. However, there are no such commercially available drug mixtures, and there is also no published evidence on the compatibility and stability of NH and FC. Thus, the primary purpose of the current research is to investigate the physical compatibility and chemical stability of NH when mixed with FC over a 72-h period in a 0.9% sodium chloride injection solution for PCA administration under storage at 4°C and 25°C.