Rejected

The increase of oxidant compounds is the most well-known reasons for the tolerance to the analgesic properties of Morphine. Additionally, the production of proxy-nitrite impairs receptors, proteins and enzymes involved in the signaling pathways of analgesia, apoptosis and necrosis. Also, we revised all patents relating to opioid tolerance control methods.

The high prevalence of chronic pain conditions combined with an over-reliance on opioid prescriptions has resulted in an opioid epidemic and a desperate need for solutions. There is some debate about whether cannabis might play a role in addressing chronic pain conditions as well as the opioid epidemic. Recent surveys suggest that a large number of people are using cannabis as a treatment for pain and to reduce use of opioids, and cannabis-derived products demonstrate at least modest efficacy in the treatment of pain in randomized controlled trials. In addition, surveillance studies from countries that have approved the use of Sativex, which is a cannabis-based product, have demonstrated that a combination of Δ9-tetrahydrocannabinol and cannabidiol has low potential for harm, is well tolerated, and is helpful to patients. Given the number of people in the United States who are already using cannabis to manage pain and opioid use in state-regulated markets, it is imperative to conduct additional research in these areas, and to disseminate information on how to minimize harm and maximize any benefits of using cannabinoids to mitigate pain and reduce opioid use. The purpose of this article is to call attention to the fact that cannabis is being used in the management of chronic pain. Thus, this article also provides a set of guidelines on how to approach using cannabis to treat pain.

Neurotransmitters released at the neural synapse through vesicle exocytosis are spatiotemporally controlled by the action of neurotransmitter transporters. Integral membrane proteins of the solute carrier 6 (SLC6) family are involved in the sodium and chloride coupled uptake of biogenic amine neurotransmitters including dopamine, serotonin, noradrenaline and inhibitory neurotransmitters including glycine and γ-amino butyric acid. This ion-coupled symport works through a well-orchestrated gating of substrate through alternating-access, which is mediated through movements of helices that resemble a rocking-bundle. A large array of commercially prescribed drugs and psychostimulants selectively target neurotransmitter transporters thereby modulating their levels in the synaptic space. Drug-induced changes in the synaptic neurotransmitter levels can be used to treat depression or neuropathic pain whereas in some instances prolonged usage can lead to habituation. Earlier structural studies of bacterial neurotransmitter transporter homolog LeuT and recent structure elucidation of the dopamine transporter (dDAT) and human serotonin transporter (hSERT) have yielded a wealth of information in understanding the transport and inhibition mechanism of neurotransmitter transporters. Computational studies based on the structures of dDAT and hSERT have shed light on the dynamics of varied components of these molecular gates in affecting the uphill transport of neurotransmitters. This review seeks to address structural dynamics of neurotransmitter transporters at the extracellular and intracellular gates and the effect of inhibitors on the ligand-binding pocket. We also delve into the effect of additional factors including lipids and cytosolic domains that influence the translocation of neurotransmitters across the membrane.

Diabetes induces sensory symptoms of neuropathy as positive (hyperalgesia), negative (hypoalgesia), or both.

Abdominal pain is a common complaint in children and its differential diagnosis includes inflammatory bowel disease (IBD). The aim of the study was to assess the diagnostic accuracy of scintigraphy with 99mTechnetium Hexamethylpropyleneamine Oxime (99mTc-HMPAO) labeled leukocytes in children with suspected IBD.

Trichobezoar is a rare cause of bowel obstruction. In general, Trichobezoars are composed of hair and usually found incidentally in patients undergoing upper gastrointestinal endoscopy or imaging. Patients diagnosed with Trichobezoar may have psychiatric disorders.

Neuropathic pain (NP) is a common public health problem that poses a major challenge to basic scientists and health-care providers. NP is a complex problem with an unclear etiology and an often-inadequate response to current medications. Despite the high number of drugs available, their limited pharmacological efficacy and side effects hamper their chronic use. Thus, the search for novel treatments is a priority. In addition to pharmaceuticals, natural extracts and food supplements are often used to help treating patients with NP. One such supplement is Noxiall, a commercially available combination of N-Palmitoylethanolamide (PEA), beta-caryophyllene; carnosic acid and myrrh. Here, we compare the efficacy of Noxiall to that of the medications gabapentin and pregabalin in the NP model of chronic constriction injury (CCI) using sciatic nerve ligation in mouse. Following CCI, mice developed a significant increase in mechanical allodynia and thermal hyperalgesia. Results showed that administration of either Noxiall, pregabalin, or gabapentin significantly attenuated mechanical allodynia. The magnitude of the Noxiall effect was comparable to that of gabapentin or pregabalin. In addition, co-administration of non-effective doses of pregabalin and Noxiall resulted in a significant decrease in NP, suggesting an additive efficacy. Noxiall was efficacious also in reducing CCI-induced thermal hyperalgesia. These findings support the rationale of using natural remedies in conjunction with classical pharmacological agents to treat chronic NP.

Giant cell arteritis is a systemic vasculitis that affects arteries of medium and large caliber, mainly the aorta artery and its main branches. It is more frequent in women older than 50 years. The most common symptoms are fever, jaw claudication, headache, hyperesthesia of the scalp and loss of vision with anterior ischemic optic nerve disease. But, in a minority of cases, less frequent symptoms are observed that delay and make more difficult the diagnosis. Here, we present the case of a 76-year-old woman who came to our consultation having pain in the oral cavity and presenting tongue and neck edema for 48 hours. She had also suffered from headaches during the previous month. Because the physical examination showed clinical signs of lingual ischemia, a presumptive diagnosis of ischemic involvement due to giant cell arteritis was considered. She started a treatment with systemic corticosteroids and a temporal artery biopsy was performed. We conclude, that giant cell arteritis should be suspected in patients presenting lingual ischemia symptoms in order to start the specific treatment early enough to avoid irreversible complications.

Chronic inflammatory pain is a common condition in the clinic, and the underlying mechanism is not being completely understood. Various studies have demonstrated that central and peripheral sensitization and synaptic plasticity could play crucial functions in chronic inflammatory pain. Moreover, families of monocarboxylate transporters (MCTs) are closely related to cellular metabolism and synaptic plasticity, and it is also reported that MCTs participate in chronic inflammatory pain. Nevertheless, there is a probability of the engaging role of MCT 1 is in chronic inflammatory pain, but its specific cellular level mechanism is yet to be investigated. In our study, we hypothesized that MCT 1 in the spinal dorsal horn plays an important part in chronic inflammatory pain.