Rejected

Diabetic neuropathic hyperalgesia is one of the most common diabetes complications. The physiopathological mechanism of hyperalgesia and the reason by which this condition affects only part of the diabetic patients still unclear. We tested whether an adaptation of primary afferent neurons to hyperglycemia could prevent the development of hyperalgesia. Hyperglycemia was induced in male Wistar rats by a daily administration of a low-dose of streptozotocin (STZ), during five consecutive days. Glycemia and mechanical nociceptive thresholds were measured at days 0, 3, 7, and 14 after starting the streptozotocin treatment. In parallel, dorsal root ganglia (DRG) neurons were collected from healthy male Wistar rats and cultured in different glucose concentrations (mimicking slow or fast increase of hyperglycemia), and used for calcium imaging and Western-blot analyses. Rats with a slow increase of glycemia did not develop hyperalgesia, while rats with a fast increase of glycemia developed hyperalgesia. DRG neurons suddenly incubated in DMEM containing a high glucose concentration, showed a significant increase of calcium influx. However, DRG neurons incubated in DMEM and receiving increasing doses of glucose, had the same calcium influx observed in control neurons. The activation of AMPK (α1/α2) was greater in L5-L6 DRG of hyperglycemic and non-hyperalgesic rats, when compared with hyperglycemic and hyperalgesic rats. Our data suggest that the onset speed of hyperglycemia could be related to the development of diabetic neuropathic hyperalgesia, as a maladaptive consequence associated with low activation of AMPK (α1/α2) in peripheral nociceptive neurons when the glycemia suddenly increases.

Digital subtraction imaging (DSI) decreases the risk of intravascular injection during cervical transforaminal epidural steroid injection (CTFESI); however, sequence acquisition and interpretation are operator-dependent skills. This study tests the reliability of a grading system to determine adequate DSI during CTFESI.

To investigate the clinical efficacy and safety of miniscalpel-needle (MSN) treatment for tension-type headache (TTH).

An increasing number of individuals are prescribed buprenorphine as medication-assisted treatment for opioid use disorder. Our institution developed guidelines for perioperative buprenorphine continuation with an algorithm for dose reduction based upon the surgical procedure and patient's maintenance dose. The objective of this study was to compare the effects of buprenorphine continuation with those of discontinuation on postoperative pain scores and outpatient opioid dispensing.

The Amazon region of Brazil experienced a large epidemic of East Central South African (ECSA) chikungunya virus (CHIKV) in 2017 and continuous transmission of CHIKV persists. The impact of chronic arthritis caused by ECSA CHIKV is unknown.

Opioid receptor agonist drugs, such as morphine, are very effective for treating chronic and severe pain; but, tolerance can develop with long-term use. Although there is a lot of information about the pathophysiological mechanisms of opioid tolerance, it is still not fully clarified. Suggested mechanisms for opioid tolerance include opioid receptor desensitisation, reduction of sensitivity G-proteins, activation of mitogen-activated protein kinase (MAPK), altered intracellular signaling pathway including nitric oxide, and activation of mammalian target of rapamycin (mTOR). One way to reduce opioid tolerance and increase the analgesic potential is to use low doses. Combination of cannabinoids with opioids has been shown to manifest reduce the opioid dose. Experimental studies revealed an interaction of the endocannabinoid system and opioid antinociception. Cannabinoid and opioid receptor systems use common pathways in the formation of analgesic effect and demonstrate their activity via G protein coupled receptors (GPCR). Cannabinoid drugs modulate opioid analgesic activity at a number of distinct levels within the cell, ranging from direct receptor associations, to post-receptor interactions through shared signal transduction pathways. This review summarizes the data indicating that with combining cannabinoids and opioids drugs may be able to produce long-term analgesic effects, while preventing the opioid analgesic tolerance.

GABA (γ-amino butyric acid) is an important inhibitory neurotransmitter in the central nervous system. Attenuation of GABAergic neurotransmission plays an important role in the etiology of several neurological disorders including epilepsy, Alzheimer's disease, Huntington's chorea, migraine, Parkinson's disease, neuropathic pain, and depression. Increase in the GABAergic activity may be achieved through direct agonism at the GABA receptors, inhibition of enzymatic breakdown of GABA, or by inhibition of the GABA transport proteins (GATs). These functionalities make GABA receptor modulators and GATs attractive drug targets in brain disorders associated with decreased GABA activity. There have been several reports of development of GABA modulators (GABA receptors, GABA transporters, and GABAergic enzyme inhibitors) in the past decade. Therefore, the focus of the present review is to provide an overview on various design strategies and synthetic approaches toward developing GABA modulators. Furthermore, mechanistic insights, structure-activity relationships, and molecular modeling inputs for the biologically active derivatives have also been discussed. Summary of the advances made over the past few years in the clinical translation and development of GABA receptor modulators is also provided. This compilation will be of great interest to the researchers working in the field of neuroscience. From the light of detailed literature, it can be concluded that numerous molecules have displayed significant results and their promising potential, clearly placing them ahead as potential future drug candidates.

Knee osteoarthritis (OA) is a painful and sometimes debilitating condition affecting an estimated 14 million people in the USA alone. Management of knee OA begins with conservative medical treatments and progresses to total knee arthroplasty. Managing pain until a patient is eligible for arthroplasty remains a key part of the treatment algorithm for knee OA. Cooled radiofrequency ablation has shown clinical effectiveness in managing knee OA pain, with a majority of patients experiencing upwards of 12 months of analgesic effect. Herein is presented an overview of the technology of cooled radiofrequency ablation and a summary of current clinical trials demonstrating the treatments effectiveness.

Frey procedure (FP) has become the standard of treatment for patients with painful chronic pancreatitis and inflammatory head mass. Biliary diversion (BD) is necessary when there is persistent biliary obstruction after adequate head coring. The aim of the present study was to assess the impact of types of biliary diversion on short-term outcome and rates of stricture recurrence.