Regional-specific changes in rat brain BDNF in a model of methamphetamine abuse.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays key roles in neuronal protection and synaptic plasticity. Changes in BDNF are associated with various pathological conditions, including methamphetamine (meth) addiction, although the effects of meth on BDNF expression are not always consistent. We have previously demonstrated region-specific effects of a chronic meth regime on BDNF methylation and expression in the rat brain. This study aims to determine the effect of chronic meth administration on the expression of BDNF protein using immunohistochemistry in the rat frontal cortex and hippocampus. Novel object recognition (NOR) as a measure of cognitive function was also determined. Male Sprague Dawley rats were administered a chronic escalating dose (0.1-4 mg/kg over 14 days) (ED) of meth or vehicle; a subgroup of animals receiving meth were also given an acute "binge" (4x6mg) dose on the final day before NOR testing. The results showed that hippocampal CA1 BDNF protein was significantly increased by 72 % above control values in the ED-binge rats, while other hippocampal regions and frontal cortex were not significantly affected. Meth-administered animals also demonstrated deficits in NOR after 24 h delay. No significant effect of the additional binge dose on BDNF protein or NOR findings was apparent. This finding is consistent with our previous results of reduced DNA methylation and increased expression of the BDNF gene in this region. The hippocampal BDNF increase may reflect an initial increase in a protective factor produced in response to elevated glutamate release resulting in neurodegenerative excitotoxicity.

Development and efficacy evaluation of a personalised self-care programme for reducing work-related musculoskeletal disorders among rubber farmers in Thailand.

Introduction: Work-related musculoskeletal disorders (WMSDs), the most common causes of work-related pain, suffering, absenteeism, and disability, are a major health concern for rubber farmers. WMSDs are persistent and frequently recur, resulting in increased health burdens for workers. Fortunately, appropriate intervention may relieve discomfort. Specified interventions have been recommended to reduce incidences of WMSD. Objective: This study aimed to develop and evaluate the efficacy of a personalised self-care programme (PSCP) for relieving pain caused by WMSDs among rubber farmers. Methods: Demographic data and details concerning the prevalence of pain regions were collected using a questionnaire adapted from the Nordic Musculoskeletal Questionnaire (IOC 1.00). The evidence gained from modified questionnaires and special tests was used to develop the PSCP. The PSCP was verified by three experts (IOC 1.00). Based on the questionnaires, only participants with a pain score of 3 or higher were recruited for the study. The PSCP's efficacy was evaluated by comparing the results before application and after 28 days. A numerical rating scale was employed to estimate the degree of pain. The pathogeneses of WMSDs were confirmed with a special test performed by a physical therapist. Additionally, the levels of interleukin (IL)-6 and IL-10 were measured to determine the PSCP's effect on inflammatory molecules. The efficacy of the PSCP was analysed using a paired t-test. Results: The results showed that farmers experienced the greatest discomfort in the lower back, followed by the shoulders, legs, and neck. Therefore, this PSCP was designed to alleviate work-related musculoskeletal pain in these body regions. A reduction in pain by two degrees was observed after 28 days of the PSCP (x‾before = 5.26, SD = 1.96, x‾after = 2.40, SD = 1.64, p < 0.001). Special tests confirmed that the number of pain regions were also decreased (x‾before = 0.089, SD = 0.067, x‾after = 0.016, SD = 0.030, p < 0.001). In addition, IL-10 levels increased (p ≤ 0.001) following the PSCP, whereas IL-6 levels remained unaltered. Conclusions: After 28 days of use, the PSCP was effective at reducing pain levels, decreasing pain regions, and promoting the production of anti-inflammatory molecules. This finding demonstrates that the PSCP could help alleviate work-related musculoskeletal pain among rubber farmers. The PSCP may be an appropriate intervention for alleviating pain.

A solid lipid particle formulation of long pepper extract reduces pain and astrocyte activation in a rat model of neuropathic pain.

OBJECTIVES: To investigate the effects of solid lipid microparticle (SLM) creams containing a long pepper extract (LPE) or piperine on neuropathy-related pain and the expression of glial fibrillary acidic protein (GFAP) as a measure of astrogliosis. METHODS: Neuropathic pain in male Spraque Dawley rats was induced by sciatic nerve ligation (SNL) and followed by treatment with LPE-SLM, piperine-SLM, capsaicin or vehicle creams. The pain score was assessed by thermal hyperalgesia test. The GFAP expression in the spinal cord was determined by immunohistochemistry. RESULTS: Pain scores were significantly increased after SNL and decreased when treated by LPE-SLM. The number of GFAP immunopositive cells was significantly increased in the SNL rats. Treated by LPE-SLM and capsaicin creams resulted in a significant reduction of the number of GFAP immunopositive cells. The LPE-SLM treated rats showed greater effects than the piperine and capsaicin preparations. CONCLUSIONS: The LPE-SLM cream has a potential effect on pain attenuation via a decrease of spinal astrocyte activation-related mechanism. The LPE in SLM preparation could provide an alternative therapeutic strategy for treating neuropathic pain.

Predictors of Low Back Pain Risk among Rubber Harvesters.

Low back pain (LBP) is a significant work-related musculoskeletal disorder among rubber farmers. This major occupational health problem was highly reported in the agricultural sector. While rubber farming is a profession with high risk of LBP, predictors for LBP remain unclear. This study was designed to investigate the risk predictors of LBP among rubber farmers during the harvesting process. A cross-sectional study was conducted between January and March 2021, in which an interviewer administered a pretested structured questionnaire. Bivariate and multivariate binary logistic regression analyses were performed. A total of 317 rubber farmers were recruited with a 100% response rate. The prevalence of LBP was 71.2% with 95% confidence interval (CI) of (0.716-1.900). Significant risk predictors were working experience (adjusted odds ratio (AOR): 1.743, 95% CI (1.034-2.937)), agricultural registration (AOR: 2.022, 95% CI (1.078-3.792)), work without training (AOR: 2.037, 95% CI (1.083-3.832)), heavy workload (AOR: 2.120, 95% CI (1.242-3.621)), and prolonged standing (AOR: 2.944, 95% CI (1.586-5.465)). Intriguingly, those with sufficient income had a reduced risk of LBP than those with insufficient income. This study confirmed that LBP is a major work-related musculoskeletal disorder among rubber farmers. The result here suggests that the five predictors reported above should be prioritized for further disease prevention.

Predictors of Musculoskeletal Pain among Primary School Students Using Smartphones in Nakhon Si Thammarat, Thailand.

School-age children increasingly use smartphones to conduct their learning activities; increasing reports of disorders related to smartphone use exist, including visual-related symptoms, stress, and musculoskeletal pain. This study aimed to examine risk factors for musculoskeletal pain among primary school students using smartphones. A cross-sectional study was conducted with 233 school-aged children in Nakhon Si Thammarat, Thailand. Data collection used a questionnaire for musculoskeletal symptoms using the Nordic Musculoskeletal Questionnaire with ISO 11,226:2000. Through Chi-square, t-test, and logistic regression analysis, factors independently associated with musculoskeletal pain were determined. An important factor in the development of musculoskeletal pain was the prolonged use of smartphones for longer than 60 min, particularly among children aged 6-9 years old. In regards to musculoskeletal pain, almost 53% of the students used their smartphones while lying down. Posing in a prone position while using a smartphone was 7.37 times more dangerous than sitting. The laying position tilts numerous organs at varying angles, especially the upper arm. The risk of musculoskeletal complaints must be reduced by educating parents, children, and the relevant government organizations about safe smartphone usage. The mentioned factors may be used to anticipate the onset of musculoskeletal pain caused by smartphone use in young children.

The effect of laying down posture while using smartphone among school children in Nakhon Si Thammarat, Thailand.

Background: Lots of children use the smartphone in lying down posture that is unappreciated posture. The postures of children while using a smartphone affect their musculoskeletal pain and can enhance Musculoskeletal Disorders (MSDs). Objective: To study the effect of lying down posture while using smartphone among school children in Nakhon Si Thammarat, Thailand. Materials and methods: This survey study employed a Descriptive Cross-Sectional Design. The population was Grade 1-6 students studying in a primary school in Nakhon Si Thammarat. There were 122 samples selected based on the Volunteer Sampling Technique under the written consent of the students' guardians. The research instruments employed in this study were: 1) Questionnaire adapted from Nordic Musculoskeletal Questionnaire asking musculoskeletal symptoms, 2) Posture Assessment using Kinovea Software to measure the angles of the muscle and postures during photo and video shooting of the smartphone users. The data were analyzed using descriptive statistics while Chi-square and Mann-Whitney U tests were used to test the mean differences. Results: There is a significant difference at p<0.05 level in mean angles of the neck, trunk, shoulder, and lower arms when using smartphones in supine and prone postures. The correlation between smartphone usage postures and musculoskeletal symptoms at the head/neck, trunk, and upper arm are found significantly different at p<0.05 level. The statistically significant difference at p<0.05 level is also found in the differences of age, length of smartphone ownership, position when using smartphone, and length of a smartphone usage in lying down positions. Conclusion: Smartphone usage in lying down positions of the participants can cause musculoskeletal pain especially in prone posture. It is recommended that guardians or relevant sectors have greater attention to smartphone usage among children to prevent their long-term musculoskeletal problems.

Pharmacogenetics of drug dependence: Polymorphisms of genes involved in GABA neurotransmission.

GABA plays a critical role in brain reward pathways via projecting signals from the ventral tegmental area to the nucleus accumbens. Activation of the reward circuitry by abused drugs induces abnormalities of GABA neurotransmission. Recent studies have indicated the involvement of GABAergic genes in the mechanism of drug dependence and its consequences. The aim of this paper is to provide a brief review of association studies of GABA-related genes with drug dependence. Single nucleotide polymorphisms (SNPs) in genes involved in GABA neurotransmission such as GABA receptor genes (GABR, GABBR), and glutamic acid decarboxylase genes (GAD) are the focus of this review as potential risk factors for drug dependence and its consequence psychosis.

Increased DNA methylation in the parvalbumin gene promoter is associated with methamphetamine dependence.

AIM: The parvalbumin (PV)-containing subgroup of GABAergic neurons is particularly affected in schizophrenia and animal models of psychosis, including after methamphetamine (METH) administration. We investigated whether METH dependence and METH-induced psychosis may involve an effect on DNA methylation of the PVALB promoter. MATERIALS & METHODS: The methylation of a PVALB promoter sequence was determined in 100 METH-dependent and 102 control subjects using pyrosequencing. RESULTS: A significant increase in PVALB methylation was observed in METH dependence and METH-induced psychosis. No significant effect on long interspersed nucleotide element-1 methylation, a measure of global DNA methylation, was observed. CONCLUSION: These results demonstrate a specific association between elevated PVALB methylation and METH-induced psychosis. This finding may contribute to the GABAergic deficits associated with METH dependence.

Association of polymorphisms in GAD1 and GAD2 genes with methamphetamine dependence.

AIM: Association between polymorphisms in GAD genes and methamphetamine (METH) dependence was investigated in the Thai population. MATERIALS & METHODS: Genotypes of rs769404 and rs701492 in GAD1 and rs2236418 in GAD2 polymorphisms were determined in 100 METH-dependent male subjects and 102 matched controls. RESULTS: The genotype and allele frequencies of rs2236418 (GAD2) were associated with METH dependence and METH with psychosis, in which the G allele was related to increased risk. The presence of the rs769404-rs701492 (GAD1) C-C haplotype was associated with METH psychosis. CONCLUSION: This study indicates that genetic variability in GAD1 and GAD2 contributes to risk of METH dependence and METH psychosis in the Thai population and indicates the role of the GABAergic system in these disorders.

Effect of Methamphetamine Exposure on Expression of Calcium Binding Proteins in Rat Frontal Cortex and Hippocampus.

Methamphetamine (METH) is a psychostimulant drug with potent effects on the central nervous system that can cause psychotic symptoms similar to those of schizophrenia. Specific alterations in GABAergic neuronal markers have been reported in schizophrenia and animal models of psychotic illness. The aim of this study was to determine whether there are changes in subpopulations of GABAergic neurons, defined by the presence of calcium binding proteins (CBPs), in animal models of METH abuse. Rats received acute (Binge) doses of 4 × 6 mg/kg, a chronic escalating dose regime (0.1-4 mg/kg over 14 days) or a combination of the two and were compared with a vehicle-administered control group. Brains were taken and sections of frontal cortex (Cg1) and hippocampus (dentate gyrus and CA1-3 regions) underwent immunostaining for three CBPs [parvalbumin (PV), calbindin (CB), and calretinin (CR)]. Significant decreases in PV-immunoreactive (IR) neurons in each METH group and all regions were observed. Smaller METH-induced deficits in CB-IR cells were observed, reaching significance primarily following chronic METH regimes, while CR-IR was significantly reduced only in frontal cortex following chronic administration. These results suggest that METH regimes in rats can induce selective deficits in GABAergic neuronal subtypes similar to those seen in schizophrenia and may underlie the psychosis and/or cognitive impairment that can occur in METH abuse and dependence.

Does elevated peripheral benzodiazepine receptor gene expression relate to cognitive deficits in methamphetamine dependence?

BACKGROUND: Methamphetamine (METH) is a neurotoxin and psychostimulant drug with potent effects on the central nervous system. With chronic METH administration, an inflammatory glial response is observed as a result of METH-induced neurotoxicity. One inflammatory marker is the peripheral benzodiazepine receptor (PBR). OBJECTIVE: The purpose of the present study was to determine whether PBR expression is changed in METH dependence and whether the changes relate to cognitive deficits. METHODS: Reverse transcriptase-polymerase chain reaction was used to investigate PBR gene expression in blood samples taken from 14 male subjects with METH dependence and 14 controls. RESULTS: The results showed a significant increase in PBR gene expression in METH dependence, suggestive of a systemic inflammatory response. The increase remained elevated for more than 1 year following abstinence from METH use, but eventually returned to normal. Subjects with elevated PBR also exhibited a deficit in one domain of the Wisconsin Card Sorting Test. CONCLUSION: The results suggest that systemic inflammatory effects can be associated with chronic METH abuse, and this may relate to the cognitive deficits seen in METH dependence. Copyright © 2016 John Wiley & Sons, Ltd.