Baclofen Treatment Research Articles

Sex differences in the interrelations between stress, craving and alcohol consumption across individuals and time during baclofen treatment for alcohol dependence

AimsRecent studies have suggested that females respond more favourably to baclofen treatment for alcohol use disorder. Females are generally more likely to drink to regulate stress reactivity and negative affect. This study thus aimed to evaluate the role of sex on the effect of baclofen on the relationship between daily alcohol consumption, stress and craving. MethodsA network analysis of fluctuations using vectorized autoregressive modelling was used to explore the relationship between daily surveys of alcohol consumption, stress and craving from daily diary data over 84 days from a randomised controlled trial of baclofen (30 mg or 75 mg per day) versus placebo in 104 participants with alcohol dependence (1, 2).Symptom interrelations across patients and across time were examined including temporal networks (time lagged), contemporaneous and between-subjects networks, and were examined for placebo and baclofen stratified by sex. ResultsOverall, between persons, there was a significant relationship between stress and drinking in placebo treated individuals in females (r = −0.70, p < 0.001) but not males (r = 0.32, p = 0.054) that was not observed in baclofen treated individuals. No relationship was observed between stress and drinking in the baclofen group for either sex (p’s < 0.45). DiscussionThere appears to be some sex-specific differences whereby baclofen abolishes an overall association between stress and drinking in females, but this is not observed in males. Network analyses may assist in elucidating the mechanism of action of alcohol pharmacotherapies such as baclofen and understanding which symptoms and mechanisms are key for effective interventions.

Results of Intrathecal Baclofen Treatment in Sixteen Spasticity Patients According to Four Different Measurement Scales:A Retrospective Analysis.

IntroductionSpasticity is a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes. It occurs as a result of overstimulation of the stretch reflex and is a component of the upper motor neuron syndrome. Intrathecal Baclofen (ITB) pump administration in patients with a diagnosis of spasticity may be a suitable option for reducing the complaints of the patients and increasing their quality of life. The aim of this study is to analyze clinically and statistically the diagnosis, treatment criteria, and post-treatment results of patients with spasticity who were treated in our clinic.Materials and MethodSixteen patients who were diagnosed with spasticity and placed on an intrathecal Baclofen pump between January 2015 and December 2020 were included in this study. An intrathecal Baclofen trial was first applied to patients who were candidates for the Baclofen pump. The spasticity levels of the patients who decided to have an intrathecal Baclofen pump were scored according to the modified Ashworth scale (MAS) and Penn spasm frequency scale (PSFS). In addition, the scaling of the patients' own conditions according to the visual analogue scale (VAS) and ambulation status according to the modified functional ambulation classification (MFAC) were recorded. All these evaluations were repeated in the preoperative, early postoperative, and follow-up periods.ResultsThe sex distribution of the patients included in the study was equal to eight women and eight men. The age distribution was between 18 and 76. The average age was 40.62 (standard deviation ±17.79). The average preoperative modified Ashworth scale score was 3.73, and the average Penn spasm frequency scale score of the patients was 3.67. The average preoperative modified functional ambulation classification score was 1.87, and the average visual analogue scale score was 6.67. At the end of the second postoperative week, the average modified Ashworth scale score was 1.80 and the average Penn spasm frequency scale score was 1.67. The modified functional ambulation classification score was 2.60 and the visual analogue scale score was 4.58. The average follow-up period of the patients was 64 months. At the end of the follow-up periods, the average late-period modified Ashworth scale score was 1.87, and the Penn spasm frequency scale score was 1.67. The average modified functional ambulation classification score was 3.00, and the average visual analogue scale score was 4.50. Statistically, there was a significant difference between preoperative and postoperative results in both modified Ashworth scale and Penn spasm frequency scale scores (P<0.05). Modified functional ambulation classification preoperative and postoperative comparison results (P<0.05) and visual analogue scale results (P<0.05) were also statistically significant. No significant difference was found between the early postoperative period and the late postoperative period in all measurements (P=1.00).ConclusionIntrathecal Baclofen administration is one of the many treatment options for spasticity. In this way, it has been shown that greater Baclofen efficacy is achieved and its side effects are reduced. It should always be remembered that the process of this treatment is teamwork that requires the participation of more than one specialty branch. Physical therapists, neurologists, pediatricians, and neurosurgeons should be included in this teamwork.

Baclofen-Induced Coma Reversible by Dialysis in a Patient Affected by Acute Kidney Injury

Baclofen is commonly used to treat muscular spasticity and other conditions such as pain, alcohol withdrawal, and myoclonus. It is contraindicated in chronic kidney disease. As it is eliminated predominantly by the kidneys, acute kidney injury can lead to acute baclofen overdose with central nervous system affection due to drug accumulation. Currently, there is no consensus about the treatment of baclofen intoxication.A 67-year-old woman was admitted with altered mental status and vomiting. Initially, she was unresponsive/lethargic and kept the intermittent ability of nonverbal communication gradually sliding into a comatose state with apneas. Initial neurologic and radiologic examinations ruled out a structural lesion of the central nervous system. Laboratory data showed acute kidney injury and suspected urinary tract infection with extremely high inflammation parameters. The patient had a history of multiple sclerosis and received daily oral baclofen. Baclofen-induced coma secondary to baclofen overdose caused by renal insufficiency was suspected and renal dialysis started within 24 hours. Cystoscopy and implantation of a ureteric stent were necessary because of obstructive nephropathy. During hemodialysis, the patient’s mental status steadily improved. The patient woke up and was oriented and cooperative. Both clinical and laboratory data were widely normalized within days.Diagnosis of baclofen overdose can be challenging, but adequate supportive therapy, including hemodialysis, should be considered to reduce the length of comatose state and the risk of aspiration pneumonia.

Prenatal GABAB Receptor Agonist Administration Corrects the Inheritance of Autism-Like Core Behaviors in Offspring of Mice Prenatally Exposed to Valproic Acid.

This study was performed to evaluate the effects of prenatal baclofen (a GABAB receptor agonist) treatment on the inheritance of autism-like behaviors in valproic acid (VPA)-exposed mice. VPA model mice (first generation, F1) that were prenatally exposed to VPA exhibited robust core autism-like behaviors, and we found that oral administration of baclofen to F1 mice corrected their autism-like behavioral phenotypes at an early age. Based on a previous epigenetics study, we mated the F1 male offspring with litter females to produce the second generation (F2). The F2 male mice showed obvious inheritance of autism-like phenotypes from F1 mice, implying the heritability of autism symptoms in patients with prenatal VPA exposure. Furthermore, we found prenatal baclofen administration was associated with beneficial effects on the autism-like phenotype in F2 male mice. This may have involved corrections in the density of total/mature dendritic spines in the hippocampus (HC) and medial prefrontal cortex (mPFC), normalizing synaptic plasticity. In this research, GABAB receptor agonist administration corrected the core autism-like behaviors of F1 mice and protected against the inheritance of neurodevelopmental disorders in the offspring of F1 mice, suggesting the potential of early intervention with GABAB receptor agonists in the treatment of neurodevelopmental disorders.

Attainment of personal goals in the first year of intrathecal baclofen treatment in dyskinetic cerebral palsy: a prospective cohort study

Purpose To assess attainment of individual treatment goals one year after intrathecal baclofen (ITB) pump implantation in individuals with dyskinetic cerebral palsy (CP). Materials and methods A multi-center prospective cohort study was conducted including 34 non-walking individuals with severe dyskinetic CP, classified as Gross Motor Function Classification System (GMFCS) IV/V, aged 4–24 years, 12 months after pump implantation. The main outcome measure was Goal Attainment Scaling (GAS). Predictors of GAS results were analyzed. Complications were registered systematically. Results Seventy-one percent of individuals with dyskinetic CP fully achieved one or more treatment goals. One or more treatment goals were partially achieved in 97% of individuals. Two factors were found to be associated with attainment of goals: Dyskinesia Impairment Scale (DIS) score at baseline and the difference in pain score between baseline and follow-up. These two variables explain 30% of the variance in the outcome. Conclusions Intrathecal baclofen is effective in achieving individual treatment goals in children and young adults with dyskinetic CP after nine to 12 months of ITB treatment. A positive outcome on treatment goals is, for a small part, associated with higher severity of dystonia at baseline and with improvement of pain during treatment. Clinical trial registration number Dutch Trial Register, number NTR3642. Implications for rehabilitation Intrathecal baclofen treatment is effective in attainment of personal treatment goals, one year after pump implantation in patients with dyskinetic cerebral palsy. A positive outcome on treatment goals is, for a small part, related to higher severity of dystonia at the start and on improvement of pain during treatment.

Surgical complications of intrathecal baclofen in children: A single centre, 20-year retrospective cohort study.

Complications of intrathecal baclofen treatment (ITB) with an implanted pump can be severe and require surgery. Surgical implantation techniques and catheter materials for continuous ITB treatment have improved over the past years with the aim to reduce complications. To assess: 1) the type and rate of complications of ITB that require surgical intervention, 2) which risk factors influence the occurrence of complications, and, specifically, 3) whether complication rate is influenced by type of catheter used. A retrospective cohort study was conducted including all children (<18 years old) in one university medical center with pump implantation between 2001 and 2017. All complications requiring surgery were recorded. Risk factors for surgical intervention were determined using multiple logistic regression analysis. Catheter related complications between two types of catheters (silicone vs coated) were compared. In total, 88 complications of ITB treatment requiring surgery were found in 47 (36.2%) out of 130 children. These included catheter-related complications (55.7% of all complications), infections (21.6%), cerebrospinal fluid leakage (14.8%), and pump-related complications (7.9%). The silicone catheter type, used until 2012, was found to be a significant risk factor for complications (Odds Ratio 3.75; 95% CI: 1.30-10.83). Since the introduction of the coated catheter type, in 2012, the rate of catheter-related complications decreased, from 0.15 to 0.10 complications per pump year. The rate of surgical complications of intrathecal baclofen in children is high, and most frequently catheter-related. The number of complications decreased since the introduction of a new, coated, catheter in 2012. This study helps to inform children and their caregivers about the risk of possible complications of ITB, and to identify directions for future improvement of ITB care.

Efficacy and Safety of Baclofen for Treatment of Alcohol Dependence: An Updated Meta-Analysis and Meta-Regression Study

Baclofen is increasingly used for alcohol dependence treatment but its use remains controversial. Therefore, this study aimed to assess the efficacy and safety of baclofen use on alcohol dependence. This is systematic review and meta-analysis of randomized controlled trials. PubMed, Science Direct, Scopus and Thai databases were systematically searched. Randomized controlled trials investigating efficacy and safety of baclofen on alcohol dependence were included. Study selection, data extraction and quality assessment were performed independently by two reviewers. The clinical therapeutic efficacy and adverse events of baclofen were assessed and were pooled using a random-effects model. Heterogeneity was assessed by I2 and chi-squared test. Sixteen studies with 1539 alcohol dependence patients were included. Baclofen increased risk of abstinence (risk ratio=1.32; 95 % confidence interval: 1.12, 1.55; p=0.0006) and abstinence duration (standard mean difference=1.07 d (95 % confidence interval: 0.13, 2.01; p=0.04) significantly. Moreover, baclofen significantly decreased heavy drinking days (standard mean difference=-1.14 d; 95 % confidence interval:-1.95, -0.34; p=0.007). However, there were no significant effects on times to relapse, craving and number of alcohol drinks. No serious adverse event associated with baclofen was reported during treatments. The meta-regression found baclofen dose was significantly associated with craving. This meta-analysis indicated that baclofen treatment in alcohol dependence patients is associated with better outcomes in risk of abstinence, abstinence duration and heavy drinking days. However, larger welldesigned studies are required to confirm these conclusions.

Presynaptic mechanisms underlying GABAB-receptor-mediated inhibition of spontaneous neurotransmitter release.

SUMMARYInhibition of neurotransmitter release by neurotransmitter substances constitutes a fundamental means of neuromodulation. In contrast to well-delineated mechanisms that underlie inhibition of evoked release via suppression of voltage-gated Ca2+ channels, processes that underlie neuromodulatory inhibition of spontaneous release remain unclear. Here, we interrogated inhibition of spontaneous glutamate and GABA release by presynaptic metabotropic GABAB receptors. Our findings show that this inhibition relies on Gβγ subunit action at the membrane, and it is largely independent of presynaptic Ca2+ signaling for both forms of release. In the case of spontaneous glutamate release, inhibition requires Gβγ interaction with the C terminus of the key fusion machinery component SNAP25, and it is modulated by synaptotagmin-1. Inhibition of spontaneous GABA release, on the other hand, is independent of these pathways and likely requires alternative Gβγ targets at the presynaptic terminal.

Novel Opipramol-Baclofen Combination Alleviates Depression and Craving and Facilitates Recovery From Substance Use Disorder-An Animal Model and a Human Study.

Substance use disorders (SUDs) are associated with depression and anxiety, with the latter being one of the major factors in substance-seeking and relapse. Due to dose-dependent sedative side effects there is limited efficacy of baclofen treatment for SUDs. Here we suggest the use of a novel combination of opipramol and baclofen (O/B) which is known to attenuate anxiety and depression, for the facilitation of recovery from SUDs. Since both opipramol and baclofen have a common downstream signal transduction, their individual doses could be reduced while still maintaining the benefits of the combination. We tested the O/B combination in both animals and patients. Rats treated with O/B showed significant attenuation in craving behavior and in relapse rate during withdrawal from cocaine. In a double-blind, placebo-controlled pilot study, conducted in a residential detoxification center, 14 males and 3 females, aged 28–60 years were assigned to a study (n = 6) and a placebo (n = 11) group (placebo group: 40 ± 10.5 years; O/B group 40 ± 10.8 years). The participants completed scales measuring depression, anxiety and craving symptoms and provided saliva samples for stress hormone examination [cortisol and dehydroepiandrosterone-sulfate (DHEA-S)]. Participants with polysubstance use disorder (PsUD) treated with O/B showed a reduction in cravings and depression and an increase in DHEA-S and in the DHEA-S/cortisol ratio. Our findings indicate a beneficial effect of O/B treatment. This study suggests a novel candidate for pharmacological treatment of patients with SUD and comorbid mood/anxiety disorders that may facilitate their rehabilitation.

Intractable singultus: a case report

Background: Intractable singultus is a rare disorder, and there are no guidelines for its management. More than 100 etiologies are described in the literature, but the etiology cannot be defined in as much as 20% of patients. Acute singultus needs no further treatment, but intractable singultus warrants thorough evaluation and treatment because it has high morbidity and mortality.Case Presentation: We present a 29-year-old male with intractable singultus accompanied by a sliding hiatal hernia, refractory to chlorpromazine and baclofen treatment, and hiatal hernia repair. The patient underwent hiatal hernia repair and Nissen fundoplication, which provided 3 days free of singultus. On the fourth postoperative day, the singultus begins 3 times a day, with episodes lasting up to 5 minutes, with a rate of 10-25 singultus per minute. The patient was discharged on postoperative day-5, hemodynamic was stable and no signs of infection were reported.Conclusion: Symptomatic treatment for intractable singultusis often unsuccessful, with serious side effects that may impair the patient's quality of life. The cornerstone of the management of intractable singultus is finding the etiology.

Carcinogenicity Evaluation of Baclofen in TgrasH2 Mice.

Baclofen is a γ-aminobutyric acid-B receptor agonist used for control of spastic muscle activity and as a treatment for alcohol abuse. The review of the nonclinical database suggested a data gap for potential carcinogenicity following long-term use. Regulatory requirements for pharmaceutical safety testing of cancer-causing potential have historically included 2-year rodent studies in rats and mice. The availability of transgenic models with greater specificity and sensitivity to carcinogens provides safety testing alternatives that align with the 3Rs. The carcinogenicity of baclofen was evaluated in CB6F1-TgrasH2 transgenic mice following daily oral administration at 45, 90, and 180 mg/kg/d for 26 weeks, preceded by a 2-week drug-conditioning period. There were no treatment-related palpable masses or neoplastic findings, and survival rates were not affected by the baclofen treatment. In conclusion, baclofen was considered as noncarcinogenic in CB6F1-TgrasH2 mice, which is consistent with results previously obtained in a 2-year rat study.

Отлучение от искусственной вентиляции легких у пациента с постгипоксической энцефалопатией и центральной гипертермией

Актуальность. Постгипоксическое повреждение центральной нервной системы часто сопровождается полиорганной дисфункцией, персистирующим неврологическим дефицитом и может осложниться центральной гипертермией. Целью данного исследования было проанализировать литературные данные о методах лечения гипертермии центрального генеза и предложить стратегию отлучения от респираторной терапии у такого пациента. Материалы и методы. Поиск литературных источников проводился в базах данных PubMed и MedLine за последние 13 лет. Поисковыми словами были «гипертермия центрального генеза» и «отлучение от искусственной вентиляции легких у детей с постгипоксической энцефалопатией». Наблюдение и лечение пациента осуществлялись на клинической базе кафедры анестезиологии и интенсивной терапии Львовского национального медицинского университета имени Данила Галицкого в отделении анестезиологии с койками интенсивной терапии КНП «Львовская областная клиническая больница «ОХМАТДЕТ» в сентябре — октябре 2018 года. Результаты. У ребенка в возрасте 7 мес. после перенесенной клинической смерти и успешного восстановления спонтанного кровообращения развились постгипоксическая энцефалопатия, синдром полиорганной дисфункции и гипертермия центрального генеза. Это привело к росту минутной вентиляции легких, тахикардии и, соответственно, проблеме с отлучением от респираторной поддержки. Кроме того, у пациента был клинически значимый гипертонус мышц нижних конечностей с постоянным спонтанным разведением в тазобедренных суставах более 180°. В лечение был добавлен баклофен в дозе 0,3 мг/кг/сут per os, которая через 7 дней была увеличена до 0,6 мг/кг/сут. На 3-и сутки с момента назначения баклофена температура тела стала стабильно ниже 38 °C, на 5-е сутки не превышала 37,5 °C. Отлучение от искусственной вентиляции легких проводилось поэтапно — от принудительно-вспомогательного режима искусственной вентиляции легких с постепенным снижением параметров поддержки до вспомогательного режима с ежедневным увеличением интервала спонтанного дыхания пациента без респираторной поддержки, начиная от 2–4 ч в дневной период времени в течение 2–3 дней и перехода к плановой вспомогательной вентиляции только в ночное время и полному отлучению от вспомогательной вентиляции. Полное отлучение от искусственной вентиляции легких произошло на 7-е сутки с момента назначения баклофена. Выводы. Контроль над лихорадкой у пациентов, перенесших повреждения центральной нервной системы, может улучшить результаты лечения, особенно если будут разработаны более эффективные стратегии мониторинга и лечения гипертермии.

Evaluation of the Effect of Intranasal Lidocaine in the Treatment of Spasticity in Patients with Traumatic Brain Injury.

BackgroundSpasticity following traumatic brain injury (TBI) is one of the most significant barriers of returning patients to their normal life. Spasticity caused by TBI does not have a specific or definitive treatment, and the clinical effect of pharmacologic treatments has not been significant.MethodsIn this single-arm study, we evaluated 15 patients. For each patient with spasticity, treatment with oral baclofen 25 mg was started three times a day as a part of standard therapy. After 48 hours, if the spasticity did not decrease by at least one score in the Modified Tardieu or Ashworth scales, lidocaine 0.5% was administered as a continuous intranasal infusion. The initial dose of lidocaine was 1 mg/min, which was gradually increased to 2 mg/min. Spasticity and the frequency of spasms were assessed by Ashworth and modified tardieu scales (MTS) and Spasm Frequency Score (SFS), respectively. Heart rate (HR), respiratory rate (RR), mean arterial blood pressure (MAP), Richmond Agitation-Sedation Scale (RASS), Glasgow Coma Scale (GCS), and arterial oxygen saturation (SPo2) of patients were recorded during nine days of treatment. All data were analyzed by SPSS version 21. P-value less than 0.05 was considered as statistically significant.ResultsOut of 15 participants in this study, 13 (86.7%) were male, and 2 (13.3%) were female (mean age: 29.26 ± 12.5 years). There were no significant differences in Ashworth Scale, Modified Tradieu Scale, RASS Score, GCS Score, MAP, SPo2 percentage, HR, RR, and the number of spasms per day between the time of initiation of treatment and the second day of baclofen treatment (P > 0.05). Evaluation of spasticity using Ashworth scale on the first and last days of lidocaine treatment showed a significant decrease in the mean spasticity (3.46 ± 0.51 and 1.46 ± 0.91, respectively; P < 0.001). Spasticity assessment using the MTS showed a significant reduction in the mean of the last day of treatment compared to the mean of the first day of treatment (3.6 ± 0.5 and 1.26 ± 0.51, respectively; P < 0.001). This decrease was also seen in the mean of the last day of treatment compared to the first day in SFS (13.3 ± 3.88 and 3.8 ± 0.51, respectively; P < 0.001). Comparison of HR, RR, MAP, RASS, GCS, and SPo2 on the first and last days of treatment did not show any statistical differences.ConclusionsAlthough continuous intranasal treatment with lidocaine can be effective in spasm reduction of patients with TBI, further studies with larger sample sizes and longer follow-up periods are required.

Pressure and length of the lower esophageal sphincter as predictive indicators of therapeutic efficacy of baclofen for refractory gastroesophageal reflux-induced chronic cough

BackgroundTherapeutic efficacy of baclofen is suboptimal in the treatment of refractory gastroesophageal reflux-induced chronic cough (GERC). The purpose of the study is to identify its therapeutic predictors in a prospective clinical study. Methods138 patients with suspected refractory GERC were treated with baclofen. Before the therapy, all the patients underwent esophageal manometry and multichannel intraluminal impedance-pH monitoring to establish the diagnosis. After the efficacy of baclofen was evaluated, a stepwise logistic regression analysis was performed to identify the therapeutic predictors of baclofen and to establish a regression prediction model. ResultsThe overall response rate of baclofen treatment was 52.2% (72/138). The lower esophageal sphincter pressure (LESP) (odds ratio (OR) = 0.592, P = 0.000) and lower esophageal sphincter length (LESL) (OR = 0.144, P = 0.008) were independent predictors of baclofen efficacy. The optimal cut-off point to predict baclofen efficacy for LESP was 11.00 mmHg, with a sensitivity of 83.7% and specificity of 79.1% while that for LESL was 2.35 cm, with a sensitivity of 81.6% and specificity of 72.1%. The highest predictive specificity (90.7%) was achieved when both LESP and LESL were jointly used. ConclusionsLESP and LESL may be used to screen the patients with refractory GERC suitable for baclofen therapy and help improve the therapeutic precision. Clinical trial registrationChiCTR- ONC-13003123.

Effectiveness and safety of cervical catheter tip placement in intrathecal baclofen treatment of spasticity: A systematic review.

ObjectiveTo evaluate the effectiveness and safety of intrathecal baclofen treatment of spasticity, administered via a cervical catheter tip.DesignA review of PubMed and the Cochrane Library up to September 2020. No restriction in study design. Two reviewers independently evaluated eligibility, extracted data and evaluated risk of bias. Studies were included in which patients were treated with intrathecal baclofen for spasticity, with the catheter tip at or above the first thoracic level, independent of diagnosis and age.ResultsThirteen studies were eligible, with a moderate to critical risk of bias. Improvement in spasticity was seen only in the upper extremity in 6% of subjects, only in the lower extremity in 2%, in both upper and lower extremities in 50% and without specification of location in 41%. Upper extremity function improved in 88% of cases. Neither drug-related (1%) nor technical (21%) complications occurred more often than in lower placement of the tip. Effects on respiratory function and sleep apnoea were not investigated.ConclusionCervically administered intrathecal baclofen seems to improve upper extremity spasticity and function, without causing more complications than thoracolumbar intrathecal baclofen. However, the mainly drug-related complications have not been thoroughly investigated and the available literature is of poor methodological quality. Further research is needed to confirm the efficacy and safety of this procedure.LAY ABSTRACTSpasticity is a common complication in central neurological disorders. It can lead to discomfort and functional limitations. To reduce spasticity, administration of baclofen via a catheter into the spinal canal has been used successfully for several years. However, this treatment often has limited effects on the upper limbs. The catheter tip is often situated in the thoracolumbar region. This review suggests that baclofen treatment via a cervically located catheter tip reduces spasticity of both arms and legs. Also, arm function improved in patients with a cervical catheter tip. Neither drug-related nor technical complications occurred more often than in lower placement of the cervical catheter tip. Few studies were found on this subject, and the available literature is of poor quality. Therefore, more research is needed to confirm the positive effect of this procedure on spasticity of the arms and to monitor for complications.

Repeated Administration of Baclofen Modulates TRPV-1 Channel Expression by PKC Pathway in Dorsal Root Ganglia of Spinal Cord in Morphine Tolerance Model of Rats

Background:Tolerance and dependence to anti-nociceptive effect of morphine restricted its use. Nowadays co-administration of morphine and other drugs suggests diminishing this tolerance. Baclofen is one of the drugs that may be beneficial in the attenuation of tolerance to morphine. Studies have shown that changes in TRPV-1 expression during administration of morphine have a pivotal role in developing morphine tolerance. Therefore, the effect of baclofen on TRPV-1 expression during chronic administration of morphine was investigated in this study. Methods:A total of 48 rats were divided into four groups of control, morphine single injection, morphine tolerance, and morphine tolerance + baclofen. To induce morphine tolerance in rats, animals received 10 mg/kg of i.p. morphine sulfate once a day for 10 days. In the treatment group, baclofen (0.5 mg/kg) was injected for 10 days, before morphine injection. Finally, to evaluate baclofen treatment on morphine analgesia and hyperalgesia, thermal hyperalgesia and formalin test were used. TRPV-1 and PKC expression and protein production in DRG of spinal cord were then evaluated by real-time PCR and Western blot. Results:In baclofen treatment group, thermal hyperalgesia and formalin test improved in comparison with morphine tolerance group. In morphine tolerance group, both TRPV-1/PKC gene expression and protein levels increased in comparison with the control group. However, following the baclofen treatment, the TRPV-1 and PKC levels decreased. Conclusion:Baclofen can enhance anti-nociceptive effect of morphine by modulating TRPV-1 channel and PKC activity.

Non-genetic factors that influence methamphetamine intake in a genetic model of differential methamphetamine consumption.

Genetic and non-genetic factors influence substance use disorders. Our previous work in genetic mouse models focused on genetic factors that influence methamphetamine (MA) intake. The current research examined several non-genetic factors for their potential influence on this trait. We examined the impact on MA intake of several non-genetic factors, including MA access schedule, prior forced MA exposure, concomitant ethanol (EtOH) access, and gamma-aminobutyric acid type B (GABAB) receptor activation. Selectively bred MA high drinking(MAHDR) and low drinking (MALDR) mice participated in this research. MAHDR, but not MALDR, mice increased MA intake when given intermittent access, compared with continuous access, with a water choice under both schedules. MA intake was not altered by previous exposure to forced MA consumption. Male MAHDR mice given simultaneous access to MA, EtOH, and an EtOH+MA mixture exhibited a strong preference for MA over EtOH and EtOH+MA; MA intake was not affected by EtOH in female MAHDR mice. When independent MAHDR groups were given access to MA, EtOH, or EtOH+MA vs. water in each case, MA intake was reduced in the water vs. EtOH+MA group, compared with the water vs. MA group. The GABAB receptor agonist R(+)-baclofen (BAC) not only reduced MA intake but also reduced water intake and locomotor activity in MAHDR mice. There was a residual effect of BAC, such that MA intake was increased after termination of BAC treatment. These findings demonstrate that voluntary MA intakein MAHDR mice is influenced by non-genetic factors related to MA access schedule and co-morbid EtOH exposure.

Non-acid Reflux: When It Matters and Approach to Management.

This narrative review focuses on the presentation, contributing factors, diagnosis, and treatment of non-acid reflux. We also propose algorithms for diagnosis and treatment. There is a paucity of recent data regarding non-acid reflux. The recent Porto and Lyon consensus statements do not fully address non-acid reflux or give guidance on classification. However, recent developments in the lung transplantation field, as well as older data in the general population, argue for the importance of non-acid reflux. Extrapolating from the Porto and Lyon consensus, we generally classify pathologic non-acid reflux as impedance events > 80, acid exposure time < 4%, and positive symptom correlation on a standard 24-h pH/impedance test. Other groups not meeting this criteria also deserve consideration depending on the clinical situation. Potential treatments include lifestyle modification, increased acid suppression, alginates, treatment of esophageal hypersensitivity, baclofen, buspirone, prokinetics, and anti-reflux surgery in highly selected individuals. More research is needed to clarify appropriate classification, with subsequent focus on targeted treatments.

The Efficacy of Baclofen to Treat Gastroesophageal Reflux disease in Children Aged 6 Months to 12 Years: A Clinical Trial Study

Background Gastroesophageal Reflux is a physiological phenomenon, which occurs in infants, children, and normal adults. Various studies have shown that Baclofen is a potent inhibitor of lower esophageal sphincter and has beneficial effects in adult reflux disease. We aimed to evaluate the Baclofen effect in pediatric Gastroesophageal disease. Materials and Methods: Children 6 months to 12 years old, with Gastroesophageal reflux disease were enrolled in this Clinical trial study. Patients referred to Taleghani Children’s Center in Gorgan, Golestan province, Iran from May to August 2019. Patients were randomly divided into two intervention group and control group. The controls received only proton pump inhibitor 1 mg per kg treatment, and intervention group received proton pump inhibitor (PPI) plus baclofen 0.25 mg per kg two times per day. Patient data including age, gender, family history, growth status, reflux symptoms, previous drug treatment history, and symptoms in two groups, were compared. Results: Fifty-four patients in the baclofen treatment group and 58 patients in the non-baclofen treatment group were included. The mean age of the patients was 6.61+ 3.55 years. The most common symptoms of all patients were abdominal pain (73.2%), nausea (73.2%), regurgitation (64.3%), and dental erosion (55.4%). The rate of recovery was significantly related to gender, with 69.9% of patients having moderate to full recovery (p = 0.017). Weight gain in baclofen treated group was significantly higher. Conclusion: The results suggest that baclofen along with routine Gastroesophageal reflux treatments in children can help reduce or improve symptoms of the disease. Due to limited studies, further studies are needed to confirm the positive effect of this drug with higher sample size.

Access to Intrathecal Baclofen Treatment for Children with Cerebral Palsy in European Countries: An SCPE Survey Reveals Important Differences.

The aim is to study access to intrathecal baclofen (ITB) for children with cerebral palsy (CP) in Europe, as an indicator of access to advanced care. Surveys were sent to CP registers, clinical networks, and pump manufacturers. Enquiries were made about ITB treatment in children born in 1990 to 2005 by sex, CP type, level of gross motor function classification system (GMFCS) and age at the start of treatment. Access to ITB was related to the country's gross domestic product (GDP) and % GDP spent on health. In 2011 population-based data from Sweden, Norway, England, Portugal, Slovenia, and Denmark showed that 114 (3.4%) of 3,398 children with CP were treated with ITB, varying from 0.4 to 4.7% between centers. The majority of the children were at GMFCS levels IV-V and had bilateral spastic CP. In Sweden, dyskinetic CP was the most commonly treated subtype. Boys were more often treated with ITB than girls (p = 0.014). ITB was reported to be available for children with CP in 25 of 43 countries. Access to ITB was associated with a higher GDP and %GDP spent on health (p < 0.01). Updated information from 2019 showed remaining differences between countries in ITB treatment and sex difference in treated children was maintained. There is a significant difference in access to ITB for children with CP across Europe. More boys than girls are treated. Access to ITB for children with CP is associated with GDP and percent of GDP spent on health in the country.