Crystell Guadalupe Guzmán-Priego

Antinociceptive synergy between diclofenac and morphine after local injection into the inflamed site

BACKGROUND Combinations of non-steroidal anti-inflammatory drugs with opioids are frequently used to reduce opioid doses required in the clinical management of acute pain. The present study was designed to evaluate the possible antinociceptive interaction between morphine and diclofenac at peripheral level in male rats. METHODS Drugs were chosen based on their efficacy in the treatment of this kind of pain and as representative drugs of their respective analgesic groups. For the formalin test, 50 μ of 1% formalin solution was injected subcutaneously into the right hind paw. The interaction between morphine and diclofenac was evaluated by using isobolographic analysis and interaction index. Drug interaction was examined by administering fixed-ratio combinations of morphine-diclofenac (1 : 1 and 3 : 1) of their respective ED30 fractions. RESULTS Diclofenac and morphine reduced flinching behavior in a dose-dependent manner during phase 2 but not phase 1 of the formalin test. Isobolographic analysis showed a synergistic interaction for the combination of morphine and diclofenac after local peripheral administration. CONCLUSIONS Data suggest that the combination of morphine with diclofenac at the site of injury is synergistic and could be useful in the treatment of wounds, bruises, rheumatisms and other painful peripheral conditions associated with an inflammatory process.

Role of NHE1 in Nociception

Intracellular pH is a fundamental parameter to cell function that requires tight homeostasis. In the absence of any regulation, excessive acidification of the cytosol would have the tendency to produce cellular damage. Mammalian Na+/H+ exchangers (NHEs) are electroneutral Na+-dependent proteins that exchange extracellular Na+ for intracellular H+. To date, there are 9 identified NHE isoforms where NHE1 is the most ubiquitous member, known as the housekeeping exchanger. NHE1 seems to have a protective role in the ischemia-reperfusion injury and other inflammatory diseases. In nociception, NHE1 is found in neurons along nociceptive pathways, and its pharmacological inhibition increases nociceptive behavior in acute pain models at peripheral and central levels. Electrophysiological studies also show that NHE modulates electrical activity of primary nociceptive terminals. However, its role in neuropathic pain still remains controversial. In humans, NHE1 may be responsible for inflammatory bowel diseases since its expression is reduced in Crohns disease and ulcerative colitis. The purpose of this work is to provide a review of the evidence about participation of NHE1 in the nociceptive processing.

Gender differences in the association between HTR2C gene variants and suicidal behavior in a Mexican population: a case–control study

Background The aim of this case–control study was to explore the association by gender between the HTR2C gene variants and suicidal behavior in a Mexican population. Subjects and methods A total of 183 suicide attempters and 208 healthy volunteers were included in this study. We genotyped five polymorphisms of HTR2C (rs547536, rs2192372, rs4272555, rs6318, and rs2428707), then measured the association by genotype, allele, and haplotype. Results In the female group, we found an association between two polymorphisms of the HTR2C (rs4272555 and rs2428707) and suicide attempts. The C allele of the single-nucleotide polymorphism (SNP) rs4272555 was associated with a decreased risk of suicide attempt (P=0.01, odds ratio =0.26, 95% confidence interval: 0.09–0.79), whereas the G allele of the SNP rs2428707 was associated with an increased risk of suicide attempt (P=0.01, odds ratio =3.68, 95% confidence interval: 1.24–10.90). No significant association was observed between the other polymorphisms studied (rs547536, rs2192372, rs6318) or haplotypes with suicide attempts. Conclusion These findings suggest a possible risk factor of the HTR2C gene in the pathology of suicidal behavior in Mexican population. More studies are necessary to confirm this association.

Peripheral and spinal TRPA1 channels contribute to formalin-induced long-lasting mechanical hypersensitivity

Background Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed by a subset of nociceptive neurons that acts as a multimodal receptor. Its activity contributes to modulate nociceptive transmission in acute inflammatory pain. However, the role of this channel in chronic pain has been less studied. The purpose of this study was to investigate the local peripheral and spinal participation of TRPA1 channels in formalin-induced long-lasting hypersensitivity. Materials and methods Formalin (1%)-induced chronic hypersensitivity was determined by the application of von Frey filaments to ipsilateral and contralateral paws and through pharmacological testing using a selective TRPA1 blocker (A-967079). TRPA1 expression in the dorsal root ganglion (DRG) and spinal cord was analyzed by Western blotting. Results Formalin (1%) injection produced acute flinching behavior (1 h) as well as secondary allodynia and hyperalgesia (12 days). Local peripheral pretreatment (10 min before) or posttreatment (6 days later) with A-967079 (1–100 µM) partially prevented and reversed, respectively, in a dose-dependent manner, long-lasting secondary mechanical allodynia and hyperalgesia evoked by 1% formalin. Likewise, intrathecal pretreatment or posttreatment with A-967079 partially prevented and reversed, respectively, formalin-induced long-lasting hypersensitivity. A-967079 (100 µM) completely abolished the pro-nociceptive effect of formalin (adjusted to pH 7.4). Finally, formalin injection increased TRPA1 protein expression in the DRG and spinal cord. Conclusion Results indicate that TRPA1 expressed in the DRG and spinal cord plays a relevant role in formalin-induced long-lasting secondary nociceptive hypersensitivity.

The role of COMT gene Val108/158Met polymorphism in suicidal behavior: systematic review and updated meta-analysis

Background It is accepted that there is a genetic factor that influences the risk of suicidal behavior. The catechol-O-methyltransferase (COMT) gene, especially the Val108/158Met polymorphism, has been associated with suicide; however, no conclusive outcome has been attained. Therefore, the aim of the present study was to assess the role of COMT Val108/158Met in suicidal behavior throughout an updated meta-analysis. Methods We performed an online search using PubMed and Web of Science (up to March 2017). Our systematic review included case-control studies of individuals who attempted suicide and completed suicide. We tested allelic, homozygous, heterozygous, dominant, and recessive inheritance models. The meta-analysis was performed in accordance with the statement of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Results The meta-analysis comprised 17 studies, which included 3,282 cases and 3,774 controls, and showed that when evaluating the overall population, the Val108/158Met polymorphism of COMT was not associated with suicidal behavior in any of the inheritance models; however, the subanalyses showed that this polymorphism exhibits a risk factor in males and a protective effect in females. Additionally, it conveyed a risk factor in Asian populations when using the allelic (OR 1.25; CI: 1.04–1.51) and recessive models (OR 1.32; CI: 1.03–1.68). Conclusion Our updated meta-analysis suggests a possible association between COMT Val108/158Met and suicidal behavior in Asian populations. However, in view of the small number of studies, these results should be considered exploratory. We recommend that more studies be performed with larger samples.

Lack of Association of Coffee Consumption with the Prevalence of Self-Reported Type 2 Diabetes Mellitus in a Mexican Population: A Cross-Sectional Study

It is estimated that almost 366 million people are currently suffering from diabetes mellitus worldwide. However, it has been suggested that coffee consumption has a protective effect against the development of type 2 diabetes mellitus. This association has been observed in many regions around the world. Today, there are no reports in Mexico regarding this association. Therefore, the aim of this study was to assess the association between coffee intake and self-reported type 2 diabetes mellitus in the southeastern part of Mexico. This study included 1277 residents of Comalcalco, a municipality of Tabasco State, Mexico. We calculated the prevalence for diabetes and performed multivariate analysis using multiple logistic regressions to evaluate the combined association with type 2 diabetes mellitus. The prevalence of the diabetes was 12.52% (95% CI: 10.67–14.38). The majority of people surveyed (77.29%; 95% CI: 74.95–79.60) indicated they were coffee drinkers. The results of multivariate analysis showed a non-significant relationship between the number of cups of coffee drank and type 2 diabetes mellitus. The adjusted odds ratio gave the following values: 1.20, (95% CI: 0.59–2.41) for non-daily consumption; 1.66 (0.82–3.34), for 1 cup of coffee peer day, and 1.49 (0.78–2.86) for 2–3 cups. Subsequently, an adjustment was made for age, gender, marital status, education, alcohol consumption, and cigarette smoking. In our population, we did not observe an association between coffee intake and its protective relationship with self-reported type 2 diabetes mellitus.

Gender differences of suicides in children and adolescents: Analysis of 167 suicides in a Mexican population from 2003 to 2013

Suicide is the second cause of death in youth population. The aim of the present study was to analyze demographic characteristics and suicide methods used, as well as to identify gender differences among Mexican children and adolescents (aged 10-17 years) that committed suicide. Between January 2003 and December 2013, 167 suicides of children and adolescents between 10 and 17 years of age were documented by the Secretary of Health of the state of Tabasco, Mexico. All sociodemographic characteristics were compared according to gender. Our sample included 67.7% males and 32.3% females (male to female 2.1:1). The predominant marital status was single (89.6%) and hanging (93.7%) was the principal method of suicide used. Both female and male adolescents were predominantly students (50%); however, female adolescents were more frequently married (17%) and were housewives (26.4%). Our results identified that hanging is the principal suicide method used by children and adolescents in Mexican population; we also detected main gender differences in terms of poisoning/drug toxicity as the method used, occupation and marital status. These results should be taken into consideration when designing suicide prevention programs due to the differences found by gender.

Characteristics of Mexican children and adolescents who died by suicide: A study of psychological autopsies

OBJECTIVE In recent years, suicide in children and adolescents has increased considerably, becoming the second cause of death in this age group. Therefore, the aim of this study was to identify characteristics and factors that could precipitate deaths by suicide in children and adolescents. METHODS Using the psychological autopsy method, we studied 28 suicide cases of children and adolescents between 10 and 17 years old. Socio-demographic factors, characteristics of the suicide and family history were documented. RESULTS The proportion of deaths by suicide was the same in females and males (50% each). Most of the suicides were performed at the child/adolescents home (78.6%) and no history of previous suicide attempts were registered (85.7%). Also, the majority of suicidal individuals came from a dysfunctional family (60.7%). CONCLUSIONS Our results identified characteristics of children and adolescents that had died by suicide, such as dying at their homes and coming from dysfunctional families. Knowing the characteristics of children and adolescents that had ended their lives by suicide should be considered in future studies to help developing preventive programs and strategies for treating suicidal behaviors in Mexican children and adolescents.

Antihyperalgesic Effects of Indomethacin, Ketorolac, and Metamizole in Rats: Effects of Metformin

Preclinical Research