Rejected

The endocannabinoid system (ECS) is known to modulate not only food intake but also pain, especially via the cannabinoid type 1 receptor (CB1R) expressed throughout the central nervous system and the peripheral tissues. Our previous study demonstrated that fasting produces an analgesic effect in adult male mice, which is reversed by intraperitoneal (i.p.) administration of CB1R antagonist (SR 141716). In the present study, we further examined the effect of CB1R expressed in the peripheral tissues. In the formalin-induced inflammatory pain model, i.p. administration of peripherally restricted CB1R antagonist (AM 6545) reversed fasting-induced analgesia. However, intraplantar administration of SR 141716 did not affect fasting-induced analgesia. Furthermore, mRNA expression of CB1R did not change in the formalin model by fasting in the dorsal root ganglia. The formalin-induced c-Fos expression at the spinal cord level was not affected by fasting, and recording from the superficial dorsal horn of the lumbar spinal cord revealed that fasting did not affect formalin-induced neural activity, which indicates minimal involvement of the spinal cord in fasting-induced analgesia. Finally, when we performed subdiaphragmatic vagotomy to block the hunger signal from the gastrointestinal (GI) system, AM 6545 did not affect fasting-induced analgesia, but SR 141716 still reversed fasting-induced analgesia. Taken together, our results suggest that both peripheral and central CB1Rs contribute to fasting-induced analgesic effects and the CB1Rs in the GI system which transmit fasting signals to the brain, rather than those in the peripheral sensory neurons, may contribute to fasting-induced analgesic effects.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an orphan disease clinically characterized by migraine, recurrent strokes, and dementia. Currently, there are no disease-modifying therapies, and it is difficult to prevent cerebral ischemic events in CADASIL patients by conventional antithrombotic medication. We hypothesized that an antimigraine agent, lomerizine hydrochloride, may prevent strokes in CADASIL patients, based on its effect on increasing cerebral blood flow.

To assess the risk of bias associated with missing outcome data in systematic reviews.

Widespread pain (WP) is emerging as a key comorbid condition in patients with chronic low back pain (CLBP). This study measured the prevalence of comorbid WP in adults with CLBP, WP predictors, and impact on patients.

Accumulating evidence indicates that toll-like receptor 4 (TLR4) plays a critical role in promoting adaptive immune responses and are definitively involved in the expansion and maintenance of the neuropathic pain. Though the application of docking in virtual-screening methods to drug discovery has some challenge, it allows directed and meaningful design of drugs for a target protein; which can lead to low costing approaches with shortcuts; resulting in evolution and discovery of promising new drugs. Nevertheless, in parallel with virtual screening methods, attendant developments in cell culture and studies must be achieved. In the present paper, we aimed to discover new drugs that have the ability to bind and inhibit TLR4 functions. So, after using the Pathway studio to investigate the biological pathways and protein interaction maps between TLR4 and neuropathy, we reported the application of the affinity-based approach of different pharmaceuticals; these agents contained all of the approved drugs; which could bind to Toll-like receptor 4 in blind high-throughput screening. Our results demonstrated that among the primary list of 1945 retrieved compounds, 39 approved compounds could be the right candidate to perform a biological test in different and conditions and as a lead for further neurophysiological and neuropathological studies and treatment of neuropathic pain.

C7-D1 disc herniation is rare in comparison with other cervical levels. The incidence rates are between 3.5% and 8%. The cervicothoracic junction disc herniation can be operated posteriorly or anteriorly. The anterior approach can be challenging because of the difficulty of access resulted from the manubrium. In this article, we present our experience about cervicothoracic junction disc herniation (C7-T1) surgery.

Hall technique (HT) is a biological approach where decay is sealed under preformed metal crowns without any caries removal, tooth preparation or local anesthesia. Dental caries is one of the most common prevailing chronic condition that affect both adults and children. Since children are anxious and apprehensive to dental treatment, their uncooperative behavior might cause hindrance in the treatment, which often leads to manage them in general anesthesia. To better address the dental care needs in pediatric patients, dental surgeons require some alternatives for management of caries and restorative treatment in children. The Hall technique is one such conservative treatment approach developed by Dr Norna Hall in 1980s.

Topical amitriptyline has been described as having mixed clinical efficacy for neuropathic pain. A few case reports using higher concentrations of this compound found clinical benefit, but many of these studies did not describe the components used in formulating the amitriptyline preparations.

Although much studied in multiple myeloma, bone events (BE) can also cause important morbidity in bone plasmacytoma patients. To our knowledge, the effect of BE on overall survival (OS) and progression to multiple myeloma free-survival (MPFS) also has never been studied.