Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror-image pain following motor fiber injury

Background: Peripheral nerve inflammation or lesion can affect contralateral healthy structures, and thus results in mirror-image pain. Supraspinal structures play important roles in the occurrence of mirror pain. The anterior cingulate cortex (ACC) is a first order cortical region that responds to painful stimuli. In the present study, we systematically investigate and compare the neuroimmune changes in the bilateral ACC region using unilateral- (spared nerve injury, SNI) and mirror-(L5 ventral root transection, L5-VRT) pain models, aiming to explore the potential supraspinal neuroimmune mechanism underlying the mirror-image pain. Methods: The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Viral injections for the designer receptors exclusively activated by designer drugs (DREADD) were used to modulate ACC pyramidal neurons. Immunohistochemistry, immunofluorescence, western blotting, protein microarray were used to detect the regulation of inflammatory signaling.Results: Increased expressions of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and chemokine CX3CL1 in ACC induced by unilateral nerve injury were observed on the contralateral side in the SNI group but on the bilateral side in the L5-VRT group, representing a stronger immune response to L5-VRT surgery. In remote ACC, both SNI and L5-VRT induced robust bilateral increase in the protein level of Nav1.6 (SCN8A), a major voltage-gated sodium channel (VGSC) that regulates neuronal activity in the mammalian nervous system. However, the L5-VRT-induced Nav1.6 response occurred at PO 3d, earlier than the SNI-induced one, 7 days after surgery. Modulating ACC pyramidal neurons via DREADD-Gq or DREADD-Gi greatly changed the ACC CX3CL1 levels and the mechanical paw withdrawal threshold. Neutralization of endogenous ACC CX3CL1 by contralateral anti-CX3CL1 antibody attenuated the induction and the maintenance of mechanical allodynia and eliminated the upregulation of CX3CL1, TNF-α and Nav1.6 protein levels in ACC induced by SNI. Furthermore, contralateral ACC anti-CX3CL1 also inhibited the expression of ipsilateral spinal c-Fos, Iba1, CD11b, TNF-α and IL-6. Conclusions: The descending facilitation function mediated by CX3CL1 and its downstream cascade may play a pivotal role, leading to enhanced pain sensitization and even mirror-image pain. Strategies that target chemokine-mediated ACC hyperexcitability may lead to novel therapies for the treatment of neuropathic pain.

The New Deep Web Drug Market Place (And the role of Bitcoin as a currency for drugs)

Drugs are a true menace to our society today. “Drug use on the rise” is an increasingly common headline in newspapers and it is well-known that this is the case. With the topic of drugs becoming more and more common in popular media, youngsters are especially influenced to try drugs. This is not a new problem, as such, and has been a relevant issue in modern society. Coupled with this, the internet plays a huge role in spreading information about emerging drugs (such as synthetic and ‘designer’ drugs). [2] This paper aims to understand the role of the internet’s Deep Web [3] and Bitcoin (and other Crypto currencies) in dealing drugs online.

Suicidal ideation, plans, and attempts and the use of psychoactive substances by adolescents

Introduction: Suicidal behavior and substance abuse constitute a serious public health problem. Aim: The study was to analyze the relationships between suicidal behaviors (ideation, plans, attempts) and substance abuse in adolescents. The authors also took into account the respondents’ motivation to attempt suicide and use psychoactive substances, as well as some demographic variables. Participants: The study involved 3493 secondary school students aged 16-17 years. The group included 69.41% girls and 30.59% boys. Methods: The participants were surveyed with a self-report questionnaire designed by one of the authors. Results: Statistically significant relationships were found between the respondents’ suicidal behaviors and the risky use of alcohol, cannabis, amphetamine, and designer drugs. Conclusions: 1. The use of psychoactive substances increases the risk of suicidal ideation and plans, as well as suicidal attempts in adolescents and young adults. 2. Significantly more respondents who report suicidal ideation, plans and attempts, in comparison to those who do not report such thoughts and behaviours, abuse alcohol and consumer cannabis, amphetamine and designer drugs to cope with problems and olster self-confidence. 3. In the group of respondents who report suicidal behaviour, psychoactive substances are consumed by significantly more men than women and by significantly more city inhabitants than people living in the country. 4. Young people, who report suicidal thoughts, plans, and attempts, are initiated into alcohol consumption at an earlier age than their non-suicidal peers.

Rapid Determination of the ‘Legal Highs’ 4-MMC and 4-MEC by Spectroelectrochemistry: Simultaneous Cyclic Voltammetry and In Situ Surface-Enhanced Raman Spectroscopy

The synthetic cathinones mephedrone (4-MMC) and 4-methylethcathinone (4-MEC) are two designer drugs that represent the rise and fall effect of this drug category within the stimulants market and are still available in several countries around the world. As a result, the qualitative and quantitative determination of ‘legal highs’, and their mixtures, are of great interest. This work explores for the first time the spectroelectrochemical response of these substances by coupling cyclic voltammetry (CV) with Raman spectroscopy in a portable instrument. It was found that the stimulants exhibit a voltammetric response on a gold screen-printed electrode while the surface is simultaneously electro-activated to achieve a periodic surface-enhanced Raman spectroscopy (SERS) substrate with high reproducibility. The proposed method enables a rapid and reliable determination in which both substances can be selectively analyzed through the oxidation waves of the molecules and the characteristic bands of the electrochemical SERS (EC-SERS) spectra. The feasibility and applicability of the method were assessed in simulated seized drug samples and spiked synthetic urine. This time-resolved spectroelectrochemical technique provides a cost-effective and user-friendly tool for onsite screening of synthetic stimulants in matrices with low concentration analytes for forensic applications.

Rapid Targeted Method of Detecting Abused Piperazine Designer Drugs

Piperazine derivatives belong to the popular psychostimulating compounds from the group of designer drugs. They are an alternative to illegal drugs such as ecstasy and amphetamines. They are being searched by consumers for recreational use due to their stimulating and hallucinogenic effects. Many NPS-related poisonings and deaths have been reported where piperazines have been found. However, a major problem is the potential lack of laboratory confirmation of the involvement of piperazine derivatives in the occurrence of poisoning. Although many methods have been published, piperazine derivatives are not always included in a routine analytical approach or targeted toxicological analysis. There is an increasing need to provide qualitative evidence for the presence of piperazine derivatives and to ensure reproducible quantification. This article describes a new rapid method of detecting piperazine derivatives in biological material, using LC-MS. All target analytes were separated in a 15 min run time and identified based on the precursor ion, at least two product ions, and the retention time. Stable isotopically labeled (SIL) internal standards: BZP-D7, mCPP-D8 and TFMPP-D4 were used for analysis, obtaining the highest level of confidence in the results. The proposed detection method provides the analytical confirmation of poisoning with piperazine designer drugs.

Molecular descriptors – an useful tool for assessing the physico-chemical properties of hallucinogenic drugs of abuse

Molecular descriptors play a fundamental role in chemistry and pharmaceutical sciences, being defined as a way to transform molecules into a set of numbers, allowing the mathematical assessment of the chemical information characterizing a molecule. This study presents the usefulness of molecular descriptors for the determination of physico-chemical properties of a series of new hallucinogenic amphetamines. Molecular descriptors of these compounds was performed with the Dragon 5.5 software. The chemometric processing of the information allowed the determination of structural correlations (similarities) between this class of designer drugs and an unknown compound.

2C-x and DOx hallucinogens: a systematic review

The drug market has seen a significant global expansion in the last decades. The synthetic designer drugs belonging to the class of amphetamines and derived phenylethylamines have experienced the greatest spread in the drug market for abuse. As phenylethylamines are organic compounds that stimulate the central nervous system of humans, many are abused as recreational drugs. A large array of substituted amphetamines can be easily synthetized by replacing one or more hydrogen atoms in the structure of phenylethylamine. Among these, the most dangerous for human health are those analogues or homologues that have hallucinogenic effects (besides the stimulant pharmacological activity), such as those belonging to the 2C-x and DOx classes of amphetamines. This review describes the physico-chemical and spectral properties of the most representative compounds of the two classes.