Baclofen Group Research Articles

Comparative Efficacy of Baclofen and Diazepam in Treating Spasticity Following Acquired Spinal Cord Injuries: A Randomized Controlled Trial

Abstract Introduction: Spasticity is a pervasive and debilitating condition. Anti-spastic medications like Baclofen and Diazepam are most commonly used for spasticity management. Objectives: The study aimed to evaluate and compare the efficacy of Baclofen with that of Diazepam in the management of spasticity following acquired spinal cord injuries. Methods: In this randomised open-label study involving 60 patients, 30 patients received 5 mg of oral Baclofen thrice daily and 30 patients received 5 mg of oral Diazepam thrice daily for the management of spasticity. The extent of spasticity was measured by Modified Ashworth Scale (MAS). The efficacy of these drugs was measured with the mean improvement in the above parameters on days 7, 14, 28, 56 and 90 from the start of pharmacotherapy. Results: Baseline muscle spasticity scores were comparable. At the endpoint, mean improvement in tone of right and left hip flexors (1.43 vs. 0.87), hip adductors (1.30 vs. 0.87), knee flexors (0.80 vs. 0.37), ankle plantar flexors (0.80 vs. 0.37) and ankle dorsiflexors (1.23 vs. 0.93) were significantly higher in Baclofen group (p<0.05), while the tone of right and left hip abductors, hip and knee extensors showed no significant difference among the groups. Conclusion: Baclofen was found to be superior to Diazepam in terms of efficacy, especially for flexor spasticity of lower limbs in acquired spinal cord injuries.

ADVERSE DRUG REACTIONS OF BACLOFEN, NALTREXONE, AND ACAMPROSATE IN PATIENTS HAVING ALCOHOL DEPENDENCE: A CROSS-SECTIONAL PHARMACOVIGILANCE STUDY

Objectives: The research aims to investigate the prevalence and patterns of adverse drug reactions (ADRs), gauge the severity of these reactions, establish causality in ADR cases, and assess the preventability of such adverse reactions. Methods: ADR information was gathered through personal interviews with patients or their relatives. Causality was assessed using the Naranjo algorithm, and a modified Hartwig and Siegel Severity Assessment Scale was used for estimating the severity of ADR. ADRs were grouped into various preventability categories based on the modified Schumock and Thornton criteria. Results: The total number of patients evaluated in the baclofen, naltrexone, and acamprosate groups was 65, 28, and 42, respectively. The most commonly reported adverse events with baclofen were nausea (31.25%), followed by fatigue (18.75%) and headache (12.50%). The majority of patients receiving acamprosate reported nausea (57.14%), followed by diarrhea (28.57%). Patients receiving naltrexone most commonly reported nausea (35.71%), followed by abdominal pain (21.43%) and headache (14.28%). Conclusion: This study shed light on the prevalence, severity, causality, and preventability of ADRs associated with anti-craving agents used to treat patients with alcohol withdrawal syndrome, providing valuable insights into the safety profiles of these medications.

Effects of Governor Vessel electroacupuncture on chloridion homeostasis in the cortex of rats with limb spasm after cerebral ischemia-reperfusion

To observe the effect of electroacupuncture (EA) stimulation of Governor Vessel on chloridion (Cl-) homeostasis and the expression of γ-aminobutyric acid (GABA) and Na+-K+-Cl- cotransporter 1 (NKCC1) in the cerebral cortex of cerebral ischemia-reperfusion injury (CIRI) model rats, so as to explore its mechanism underl-ying alleviating limb spasm after stroke. Forty-five male SD rats were randomly divided into normal, sham-operation, model, EA and baclofen groups, with 9 rats in each group. The CIRI model was established by occlusion of the middle cerebral artery and reperfusion. EA(100 Hz) was applied to "Dazhui" (GV14), "Jizhong"(GV6) and "Houhui" for 30 min. Rats of the baclofen group received gavage of baclofen solution (0.4 mg/kg, 1 mL/100 g), once daily for 7 consecutive days. Neurological deficit score was assessed according to Zea Longa's method. The muscular tone of quadriceps femoris of the limb was evaluated by modified Ashworth scale and electrophysiological recor-ding methods, separately. TTC staining was used to detect cerebral infarction volume, and the brain water content of rats in each group was determined by wet and dry weight method. The contents of Cl- and GABA in the cerebral cortex were detected by colorimetric method, and the expression levels of NKCC1 mRNA and protein in the cerebral cortex were detected by quantitative real-time PCR and Western blot, separately. No significant differences were found between the normal and sham-operation groups in all the indexes. Compared with the normal and sham-operation groups, the neurological deficit score, modified Ashworth muscle tone score, brain water content, cerebral infarct volu-me percent, Cl- content and expression levels of NKCC1 mRNA and protein were all evidently increased (P<0.01), and muscle tone of electrophyiological electromyogram (EMG) signal and GABA content were strikingly decreased (P<0.01) in the model group. Compared with the model group, both EA and baclofen groups had an obvious increase in EMG signal displayed muscle tone, and GABA content (P<0.05, P<0.01), and a marked decrease in the neurological deficit score, modified Ashworth score, brain water content, cerebral infarct percent, Cl- content and expression levels of NKCC1 mRNA and protein (P<0.05, P<0.01). EA stimulation of acupoints of the Governor Vessel can improve the degree of limb spasm and reduce the degree of cerebral edema and infarction in rats with stroke, which may be related to its functions in protecting Cl- homeostasis, up-regulating GABA concentration, and down-regulating the expression of NKCC1 protein and mRNA in the cerebral cortex.

Protective Effect of Baclofen on Ovarian Cystogenesis and Morphine-Induced Lipid Profile Change in Female Rats.

Morphine induces ovarian cysts that cause obesity and disrupt sex hormone secretion. Baclofen, a gamma-aminobutyric acid receptor agonist, can help regulate sex hormones and reduce harmful blood lipids by protecting against morphine-induced gamma-aminobutyric acid inhibition. We investigated the prophylactic effect of baclofen in rats receiving morphine by comparing with the untreated groups. Forty eight female Wistar rats were randomly divided into several groups, including control (saline 1 mL/kg, i.p.), morphine (5 mg/kg, i.p.), baclofen (10, 20, and 30 mg/kg, i.p.), and baclofen (10, 20, and 30 mg/kg) before morphine (5 mg/kg). Twenty four hours after the treatment, blood and serum samples were taken to check the levels of gonadotropins (LH & FSH) and lipid profile. The ovaries and uterus were also studied, and a proinflammatory nitric oxide (NO) diagnostic test was completed. The results were analyzed using analysis of variance (α = 0.05). In comparison with the control group, the levels of LH and not FSH decreased in the morphine group and the number of ovarian cysts was more in the morphine group. These problems were not observed in the group of baclofen alone and baclofen + morphine. However, the triglyceride level increased slightly in the baclofen 30 mg/kg + morphine group. But the LDL level somewhat decreased. The proinflammatory NO system did not show significant activation in the ovary and uterus, except for the baclofen 10 mg/kg + baclofen group. Morphine can cause ovarian cysts by lowering LH but baclofen prophylaxis can protect reproductive properties by adapting major metabolic changes.

Safety of baclofen versus tizanidine for older adults with musculoskeletal pain.

Baclofen and tizanidine are both muscle relaxants that carry the risk for neuropsychiatric events in older adults but there is a lack of data directly comparing their safety. This study aimed to investigate the relative risk between these two medications in causing injury and delirium in older adults. This was a retrospective cohort study that was completed in an integrated healthcare system in the United States and included patients aged 65 years or older who started baclofen or tizanidine for the treatment of musculoskeletal pain from January 2016 through December 2018. Outcomes included new incidence of injury (concussion, contusion, dislocation, fall, fracture, or other injuries) and delirium. The cohort was followed from the initiation of therapy until the first occurrence of any of the following events: end of the index drug exposure, end of health plan membership, death, or the study end date of December 31st, 2019. Descriptive statistics were used to compare baseline patient characteristics between baclofen and tizanidine treatment groups. Cox proportional hazards model was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals. The final study cohort included 12,101 and 6,027 older adults in the baclofen and tizanidine group respectively (mean age 72.2 ± 6.2 years old, 59% female). Older adults newly started on baclofen had a greater risk of injury (HR=1.54, 95% CI=1.21-1.96, P=< 0.001) and delirium (HR=3.33, 95% CI=2.11-5.26, p=<0.001) compared to those started on tizanidine. The results of this study suggest that baclofen is associated with higher incidences of injury and delirium compared to tizanidine when used for the treatment of musculoskeletal pain. Future studies should investigate if these risks are dose-related and include a comparison group not exposed to either drug.

Effects of baclofen on insular gain anticipation in alcohol-dependent patients — a randomized, placebo-controlled, pharmaco-fMRI pilot trial

RationaleOne hallmark of addiction is an altered neuronal reward processing. In healthy individuals (HC), reduced activity in fronto-striatal regions including the insula has been observed when a reward anticipation task was performed repeatedly. This effect could indicate a desensitization of the neural reward system due to repetition. Here, we investigated this hypothesis in a cohort of patients with alcohol use disorder (AUD), who have been treated with baclofen or a placebo. The efficacy of baclofen in AUD patients has been shown to have positive clinical effects, possibly via indirectly affecting structures within the neuronal reward system.ObjectivesTwenty-eight recently detoxified patients (13 receiving baclofen (BAC), 15 receiving placebo (PLA)) were investigated within a longitudinal, double-blind, and randomized pharmaco-fMRI design with an individually adjusted daily dosage of 30–270 mg.MethodsBrain responses were captured by functional magnetic resonance imaging (fMRI) during reward anticipation while participating in a slot machine paradigm before (t1) and after 2 weeks of individual high-dose medication (t2).ResultsAbstinence rates were significantly higher in the BAC compared to the PLA group during the 12-week high-dose medication phase. At t1, all patients showed significant bilateral striatal activation. At t2, the BAC group showed a significant decrease in insular activation compared to the PLA group.ConclusionsBy affecting insular information processing, baclofen might enable a more flexible neuronal adaptation during recurrent reward anticipation, which could resemble a desensitization as previously observed in HC. This result strengthens the modulation of the reward system as a potential mechanism of action of baclofen.Trial registrationIdentifier of the main trial (the BACLAD study) at clinical.gov: NCT0126665.

The effect of oral baclofen and botulinum toxin treatments in hemiplegic spasticity on the nociceptive flexor reflex: A randomized clinical trial.

This study aimed to analyze the effect of oral baclofen treatment and botulinum toxin type A (BT-A) injection treatment in hemiplegic patients with spasticity on the electromyographic nociceptive flexor reflex (NFR) threshold. A total of 29 spastic hemiplegic patients (20 males, 9 females; mean age: 52.9±10.1; range, 27 to 64) with Modified Ashworth Scale (MAS) grades 2-4 were included in the prospective, randomized study between May 2018 and March 2019. The patients were divided into two groups: the BT-A group consisted of 15 patients that underwent a BT-A injection and the baclofen group consisted of 14 patients treated with baclofen. Modified Ashworth Scale, Visual Analog Scale (VAS), Barthel daily life activity index, and NFR threshold values were used in the evaluation of the patients before and after the treatment at the sixth week. The motor evaluation of the patients was performed using Brunnstrom motor staging. In both groups, MAS and VAS values decreased significantly compared to pretreatment (p<0.05). There was a significant decrease in ankle MAS score (p<0.001) and a significant increase in Brunnstrom hand recovery stages in the BT-A group compared to pretreatment (p=0.020). While the NFR threshold statistically significantly increased in the baclofen group compared to pretreatment (p=0.007), there was no significant change in the BT-A group (p=0.669). These results suggest that BT-A injections do not cause a significant change in the NFR threshold in the treatment of spasticity.

Role of anti-craving drugs baclofen and topiramate in the maintenance of abstinence in alcohol dependence syndrome

Background: Alcohol craving is psychological condition related to motivation. Craving is risk factor for relapse in alcohol dependence syndrome. No gold standard therapy is available; many therapeutic agents are under various evaluation stages. Objectives: To evaluate role of anti-craving drugs baclofen and topiramate in maintenance of abstinence in alcohol dependence syndrome Methods: From March to October 2018, an open-label interventional study with 70 sample size was conducted at Nobel Medical College, following ethical clearance. Age range for inclusion was 20-60, with no history of psychotropic use, whereas history of psychiatric illness and use of substance, excluding nicotine were excluded. After written informed consent patients were admitted for detoxification, and after detoxification, anti-craving therapy was started with topiramate and baclofen and asked for follow-up at two, four, and six weeks. Clinical withdrawal assessment scale was used for withdrawal symptoms and obsessive-compulsive drinking scale (OCDS) for progress in craving. Baclofen at 20 mgs/day, topiramate at 50 mgs/day, were prescribed and increased as required at follow-up. Results: Maximum daily dose of baclofen was 24.29 ± 2.19 mg and topiramate 120 ± 33.21 mg. Baclofen group patients had significant improvement in second week (OCDS T score 16.41± 9.52) while topiramate group showed significant improvement (OCDS T score 17.70 ± 7.57) after four weeks. Major side effects were tremors 8.10% in topiramate group, headache was 5.40% in both groups. Conclusion: Baclofen and topiramate were equally effective at six weeks for controlling cravings. Baclofen started to show significant improvements after two weeks of trial.

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.

Clinical trial: a controlled trial of baclofen add-on therapy in PPI-refractory gastro-oesophageal reflux symptoms.

Proton pump inhibitors (PPI) have no effect on non-acid reflux events which can continue to provoke gastro-oesophageal reflux disease (GERD) symptoms. Baclofen, a γ-aminobutyric acid agonist, can decrease non-acid reflux but its symptomatic benefit in refractory GERD symptoms is understudied. To assess the efficacy of baclofen 10mg t.i.d. vs placebo as add-on therapy in PPI-refractory GERD symptoms, in a randomised, double-blind, placebo-controlled study. Patients with persisting typical GERD symptoms on b.i.d. PPI therapy were randomised to 4 weeks of baclofen 10mg or placebo t.i.d. Before and after treatment, patients underwent 24 h impedance-pH monitoring on-PPI. Throughout the study, patients filled out ReQuest diaries. Data were analysed using mixed models. About 60 patients were included (age 47.5 years [range 19-73], 41f/19 m), 31 patients were randomised to baclofen. One patient withdrew consent and five in the baclofen group stopped treatment due to side effects. There was a trend towards a better response for general wellbeing in the baclofen-treated group compared to placebo (p= 0.06). When subdividing patients according to symptom association probability (SAP), only the SAP+ (n= 25) group improved significantly with baclofen (pcorr = 0.02), and worsened with placebo (pcorr = 0.008). The total number of reflux events decreased over time (p= 0.01), mainly due to the baclofen condition (pcorr = 0.1). The number of reflux events with a high proximal extent dropped significantly after baclofen (pcorr = 0.009), but not placebo. Baclofen decreases several reflux parameters in PPI refractory GERD symptoms, but pH-impedance monitoring is necessary before treatment as only SAP+ patients experience clinical benefit after 4 weeks.

BPSS Award

Background:Alcohol dependence syndrome is a global illness and anticraving medications are one of its management approaches. Understanding of mechanism of action of anticraving agents in alcohol dependence syndrome (ADS) is limited.Aim:The authors investigated early changes of central glutamate and GABA with Acamprosate and Baclofen among patients with ADS.Methods:Forty patients with ADS were recruited with purposive sampling. At the end of detoxification (CIWA-Ar<10) central glutamate and GABA were measured with magnetic resonance spectroscopy. SADQ, PACS were administered. Either Acamprosate or Baclofen was started with double blind random allocation. After 25 days of starting Baclofen or Acamprosate measures were repeated.Results:Both groups had shown comparable changes in craving, glutamate, and GABA levels. SAD-Q, PACS baseline and CIWA-Ar baseline were negatively corelated with GABA change in Baclofen group raising a speculation that whether Baclofen would be more effective in less severe dependence or vice-versa. In Acamprosate group CIWA-Ar baseline was positively corelated with glutamate change. Baseline glutamate was negatively corelated with glutamate change in both groups but was positively correlated with GABA change in Acamprosate group only speculating that Acamprosate could be more effective than Baclofen in more severe alcohol dependence.Conclusions:Our study has shown comparable changes in Glutamate and GABA at anterior cingulate cortex during early post-detoxification period both for Baclofen and Acamprosate.

Evaluating the use of baclofen as adjunct treatment for muscle tension dysphonia

ObjectiveTo explore whether use of baclofen as adjunct treatment to voice therapy (VT) led to improvement in subjective throat symptoms in patients with primary muscle tension dysphonia (MTD). MTD is associated with excessive paralaryngeal muscle contraction, and baclofen is a muscle relaxant. Study designCross-sectional, questionnaire-based study. MethodsAn initial pool of patients, who were diagnosed with primary MTD and received 1+ VT session(s) at a single tertiary-care center from 2015 to 2019, were placed into either a baclofen group (prescribed 10 mg baclofen t.i.d. PRN along with VT) based on symptomatology or non-baclofen group (VT alone). They were administered questionnaires via postage mail or phone that included the Voice Handicap Index-10 (VHI-10), Reflux Symptom Index (RSI), and other survey elements. A retrospective chart review collected demographic and other clinical data from recruited participants. ResultsA total of 314 non-baclofen and 63 baclofen patients met the inclusion criteria of this study, with 37 non-baclofen patients (mean age = 47.5 years, 62.2% female) and 15 baclofen patients (mean age = 45.5 years, 73.3% female) recruited. There was no significant difference in mean [SD] VHI-10 scores (11.30 [8.20] vs. 12.60 [10.75]; p = 0.638) and RSI scores (13.46 [10.44] vs. 16.20 [10.65]; p = 0.398) between non-baclofen and baclofen groups, respectively. ConclusionThere was no significant difference in voice psychometric outcomes between non-baclofen and baclofen groups, measured primarily by the VHI-10 and RSI questionnaire components. Further studies are warranted to assess the efficacy and safety of baclofen as a therapeutic option for MTD.

Effect of electro-acupuncture therapy on limb spasm and excitability of motor neurons in stroke rats.

To investigate the effect of electro-acupuncture therapy on limb spasm and excitability of motor neurons in stroke rats. Ischemic stroke model was induced with middle cerebral artery embolization in SD rats. Thirty-three modeled rats were randomly divided into model group, electro-acupuncture group, and baclofen group with 11 rats in each group, and another 10 rats were taken as sham operation group. The electro-acupuncture group and the baclofen group were treated with electro-acupuncture and baclofen tablets respectively. The model group and the sham operation group had no intervention. The neural function was evaluated with Bederson's scale and balance beam test; the muscle tension was measured with electrophysiography; the pathological changes of brain tissue was examined with HE staining; the content of glutamic acid (Glu) and γ-aminobutyric acid (GABA) in rat cerebral cortex was analyze with enzyme linked immunosorbent assay (ELISA) method, the expression of metabotropic glutamate receptor 1a () and γ-aminobutyric acid type B receptor subunit 1 () mRNA were detected with RT-qPCR. Compared with the model group, the neurological function scores of the electro-acupuncture group and the baclofen group showed a downward trend at d7 after operation (all >0.05), and the neurological function scores of the electro-acupuncture group and the baclofen group were significantly decreased at d12 after the operation (all <0.05). Compared with sham operation group, the electrophysiological results of model group, electro-acupuncture group and baclofen group were significantly lower (all <0.05), and there was no statistical difference in the electrophysiological results of the model group, electro-acupuncture group and baclofen group at d7 after operation (all >0.05). Compared with the model group, the electrophysiological results of the electro-acupuncture group and baclofen group were significantly increased after operation (all <0.05). The results of HE staining showed that there was no cell edema and degeneration in the sham operation group, no pyknosis of the nucleus, and no bleeding in the interstitium. Cell edema and degeneration and mesenchymal congestion appeared in the model group. Compared with the model group, the cytoplasmic edema and degeneration and the interstitial bleeding in the electroacupuncture group and the baclofen group were reduced. Compared with sham operation group, the Glu content and the relative expression of mRNA was increased in the model group, electro-acupuncture group and baclofen group, while the GABA content and the relative expression of mRNA decreased (all <0.05). Compared with model group, the Glu content and the relative expression of mRNA in the electro-acupuncture group and baclofen group decreased, and the GABA content and relative expression of mRNA increased (all <0.05). Electro-acupuncture may improve limb spasm after stroke through regulating the expression of Glu and GABA in the cerebral cortex and the excitability of motor neurons in rats.

Effect of High-Dose Baclofen on Agitation-Related Events Among Patients With Unhealthy Alcohol Use Receiving Mechanical Ventilation

Unhealthy alcohol use can lead to agitation in the intensive care unit (ICU). To assess whether high-dose baclofen reduces agitation-related events compared with placebo in patients with unhealthy alcohol use receiving mechanical ventilation. This phase 3, double-blind, placebo-controlled, randomized clinical trial conducted in 18 ICUs in France recruited adults receiving mechanical ventilation who met criteria for unhealthy alcohol use. Patients were enrolled from June 2016 to February 2018; the last follow-up was in May 2019. Baclofen (n = 159), adjusted from 50 to 150 mg per day based on estimated glomerular filtration rate, or placebo (n = 155) during mechanical ventilation up to a maximum of 15 days before gradual dose reduction over 3 to 6 days. The primary end point was the percentage of patients with at least 1 agitation-related event over the treatment period. Secondary outcomes included duration of mechanical ventilation, length of ICU stay, and 28-day mortality. Among 314 patients who were randomized (mean age, 57 years; 60 [17.2%] women), 313 (99.7%) completed the trial. There was a statistically significant decrease in the percentage of patients who experienced at least 1 agitation-related event in the baclofen group vs the placebo group (31 [19.7%] vs 46 [29.7%]; difference, -9.93% [95% CI, -19.45% to -0.42%]; adjusted odds ratio, 0.59 [95% CI, 0.35-0.99]). Of 18 prespecified secondary end points, 14 were not significantly different. Compared with the placebo group, the baclofen group had a significantly longer median length of mechanical ventilation (9 vs 8 days; difference, 2.00 [95% CI, 0.00-3.00]; hazard ratio [HR] for extubation, 0.76 [95% CI, 0.60-0.97]) and stay in the ICU (14 vs 11 days; difference, 2.00 [95% CI, 0.00-4.00]; HR for discharge, 0.70 [95% CI, 0.54-0.90]). At 28 days, there was no significant difference in mortality in the baclofen vs placebo group (25.3% vs 21.6%; adjusted odds ratio, 1.24 [95% CI, 0.72-2.13]). Delayed awakening (no eye opening at 72 hours after cessation of sedatives and analgesics) occurred in 14 patients (8.9%) in the baclofen group vs 3 (1.9%) in the placebo group. Among patients with unhealthy alcohol use receiving mechanical ventilation, treatment with high-dose baclofen, compared with placebo, resulted in a statistically significant reduction in agitation-related events. However, considering the modest effect and the totality of findings for the secondary end points and adverse events, further research is needed to determine the possible role of baclofen in this setting and to potentially optimize dosing. ClinicalTrials.gov Identifier: NCT02723383.

Does Baclofen induce changes in testicular histology and seminal fluid analysis in rat?

Baclofen has a central acting effect, so clinicians have been utilized it chiefly for treating the spasticity of spinal origin. Nowadays, off-labeling use of baclofen with high doses is frequently increased. Despite of the extensive research studies on the effectiveness of baclofen, the reports on its histological effects on testes and on sperm parameters we insufficient. This work aims to assess the histological influences of baclofen on rats' testes and on several sperm characteristics after administration for 8 weeks. Twenty-two male rats at age of peripuberty (8weks) that were categorized into two groups. Group I (control group) includes 10 rats which were gavaged with 1 ml/day of distilled water daily. Group II (baclofen's group) includes 12 rats which were received baclofen 14.5 mg/kg for 8 weeks via gavage. At the end of the designed work, euthenization was done and the testes were excised from each rat, the epididymis samples were obtained and prepared for examination under light microscope. This study revealed that rats that were administered with 14.5mg/kg/day of baclofen for 8 weeks showed changes in the sperms parameters with several testicular histological alterations in their sections in comparison with those of controls. The percentage of the live sperms of rats (baclofen's group was lower than that of control group). Features of sloughing inside seminiferous tubules' lumen are frequently seen among these sections with mild decrease in the diameter of seminiferous tubules. Evidence of decreased Johnsen's scores (spermatogenic index -SI) was noticed in some sections, and decreasing of the frequency of seminiferous tubules that possess spermatozoa was obviously noticed. Moreover, disorganization of seminiferous tubules is shown in these sections. In addition, sections of rats of baclofen group revealed features of necrosis of seminiferous tubules, presence of degenerated spermatogenic layer, features of apoptosis, and presence of gaps in the seminiferous epithelium of degenerated tubules. Different alterations of sertoli cells as vacuolation, and detachment sertoli cells are noticed in sections of rats that were administered with baclofen. The chronic administration of rats with 14.5 mg/kg with baclofen induced effects on sperm parameters and testicular histology. however, the testicular histological alterations were more obvious. Further works are needed to clarify mechanism that stands behind these effects.

The Histologic Effect of Baclofen in Rat’s brain: An Experimental Study

Background: Baclofen is the only clinically available metabotropic GABAB receptor agonist. Several reports has been discussed the efficacy of baclofen but the available data on its effect of the behavior and brains' histology are still limited.Objectives: This work aims to assess the effects of long term exposure to baclofen (8weeks) on behavior and brains' histology in ratsMethods: Analysis of data of Twenty five healthy male Albino rats were performed. Rats weighing about 200–210 g with mean age of 65 days were randomly selected and categorized into three groups: Group 1(LD50 group): included five rats that gavaged with single dose of baclofen to test the LD50 of drug (145mg per Kg) .Group 2. (control group):included eight rats were gavaged with distilled water for 2 months. Group 3.(baclofen group): included 12 rats gavaged with 15mg/kg of baclofen (1/10th LD50) for 2 month. Behavioral Tests were conducted on all animals in group 2 and 3 including: Open-field test ,Open -field habituation task ,and object recognition(Novel) to examine the influence of drug on the cognition of rats. All animals were euthanized with ether after 24hours of last day of treatment. Brains were excised and collected from rats of group 2 and 3.Fixation of tissues was done using buffered solution of ten percent of formalin for twenty four hours with paraffin wax embedding. Sectioning and staining by hematoxylin and eosin protocol (H&E) and prepared to be examine histologically. To differentiate between the data of group 2 and 3 ,statistical analysis was performed by 1- way analysis of variance (ANOVA) .Least significant difference test with Duncan test was used . Value of P of equal or less than 0.05 means the difference is significant .Results: This study revealed that the rats of baclofen group traveled a greater total distance(in both sessions) when compared with those of control indicating their hyperactivity. The zone specific analysis showed that the rats that were administered with baclofen consumed markedly greater time nearby the walls in the peripheral part in the arena throughout the first and 2nd 15- min session in comparison with those of control group indicating the generalized hyperactivity and exploration. Rats of control group preferred the novel object in comparison with those of baclofen group. However there is no marked difference in the index of discrimination among rats of group 2 and 3. Histological sections of rats’ brains in group that were administered with 15mg/kg of baclofen for 2 month( baclofen group) revealed a diminished thickness in the pyramidal cells’ layer, irregular faintly stained cells with shrinkage in the some pyramidal nerve cells, dark staining cytoplasm and losing the characteristics of their nuclei.Conclusions:Chronic administration with baclofen (15mg/kg/day/2months) induces changes in the brain histology in rats, however, baclofen has no adverse effect on the behavior. To the best of our information, our work is the 1st that focus on the influence of baclofen on both the behavior and brains' histology. Our data suggesting that baclofen may have clinical utility.

Baclofen-induced Changes in the Resting Brain Modulate Smoking Cue Reactivity: A Double-blind Placebo-controlled Functional Magnetic Resonance Imaging Study in Cigarette Smokers.

ObjectiveSmoking cue-(SC) elicited craving can lead to relapse in SC-vulnerable individuals. Thus, identifying treatments that target SC-elicited craving is a top research priority. Reduced drug cue neural activity is associated with recovery and is marked by a profile of greater tonic (resting) activation in executive control regions, and increased connectivity between executive and salience regions. Evidence suggests the GABA-B agonist baclofen can reduce drug cue-elicited neural activity, potentially through its actions on the resting brain. Based on the literature, we hypothesize that baclofen’s effects in the resting brain can predict its effects during SC exposure.MethodsIn this longitudinal, double blind, placebo-controlled neuropharmacological study 43 non-abstinent, sated treatment-seeking cigarette smokers (63% male) participated in an fMRI resting-state scan and a SC-reactivity task prior to (T1) and 3 weeks following randomization (T2; baclofen: 80 mg/day; n = 21). Subjective craving reports were acquired before and after SC exposure to explicitly examine SC-induced craving.ResultsWhole-brain full-factorial analysis revealed a group-by-time interaction with greater resting brain activation of the right dorsolateral prefrontal cortex (dlPFC) at T2 in the baclofen group (BAC) (p FWEcorr = 0.02), which was associated with reduced neural responses to SCs in key cue-reactive brain regions; the anterior ventral insula and ventromedial prefrontal cortex (p FWEcorr < 0.01). BAC, but not the placebo group reported decreased SC-elicited craving (p = 0.02).ConclusionResults suggest that baclofen mitigates the reward response to SCs through an increase in tonic activation of the dlPFC, an executive control region. Through these mechanisms, baclofen may offer SC-vulnerable smokers protection from SC-induced relapse.

Waggle needling wields preferable neuroprotective and anti-spastic effects on post-stroke spasticity rats by attenuating γ-aminobutyric acid transaminase and enhancing γ-aminobutyric acid.

Waggle needling, a classical anti-spastic needling technique characterized by combination of acupuncture with joint movement, has gained increasing popularity of spasticity treatment in China. This study was designed to compare the anti-spastic effect of waggle needling to the routine needling and to explore its underlying mechanism. We established post-stroke spasticity model based on ischemia stroke operation (middle cerebral artery occlusion). Rats were divided into six groups: normal control group, sham-operated control group, ischemia stroke model group, waggle needling group, routine needling group and baclofen group. Neurological function and muscle tone were assessed by the Zea Longa score and modified Ashworth scale, respectively. Indirect muscle tone was testified with electrophysiological recording. Cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride staining. The concentrations and expressions of γ-aminobutyric acid transaminase (GABAT) and γ-aminobutyric acid (GABA) were detected by enzyme-linked immunosorbent assay and western blot assay. Waggle needling markedly alleviated neurological deficits, decreased cerebral infarction and eased muscle tone; simultaneously, attenuated GABAT and enhanced GABA expression in the cortical infarct regions in comparison with the routine needling (P < 0.01), yet showed similar therapeutic effect to the baclofen group (P > 0.05). These results preliminary supported that waggle needling as a potential promising non-pharmacological intervention for the treatment of cerebral ischemia and spasticity.

Is R(+)-Baclofen the best option for the future of Baclofen in alcohol dependence pharmacotherapy? Insights from the preclinical side.

For several decades, studies conducted to evaluate the efficacy of RS(±)-Baclofen in the treatment of alcohol dependence yielded contrasting results. Human and animal studies recently questioned the use of the racemic drug in patients since a potential important role of the different enantiomers has been revealed with an efficacy thought to reside with the active R(+)-enantiomer. Here we conducted experiments in the postdependent rat model of alcohol dependence to compare the efficacy of R(+)-Baclofen or S(-)-Baclofen to that of RS(±)-Baclofen on ethanol intake, seeking, and relapse. R(+)-Baclofen was more effective than RS(±)-Baclofen in reducing ethanol intake and seeking during acute withdrawal and during relapse after abstinence. We also used an original population approach in order to identify drug responders. We found a significant proportion of responders to S(-)-Baclofen and RS(±)-Baclofen, displaying an increase in ethanol intake, and this increasing effect on alcohol intake was not seen in the R(+)-Baclofen group. At an intermediate dose of R(+)-Baclofen, devoid of any motor side effects, we identified a very large proportion of responders (75%) with a large decrease in ethanol intake (90% decrease). Finally, the response to RS(±)-Baclofen on ethanol intake was correlated to plasma level of Baclofen. R(+)-Baclofen and RS(±)-Baclofen were effective in reducing sucrose intake. Our study has important clinical implication since it suggests that the wide variability in the therapeutic responses of patients to RS(±)-Baclofen may come from the sensitivity to the R(+)-Baclofen but also to the one of the S(-)-Baclofen that can promote an increase in ethanol intake.

Comparison of Baclofen and Tizanidine in Reducing Spasticity in Cerebral Palsy: A Randomized Control Trial

Background: Cerebral palsy is the most common chronic motor disability that begins in childhood with the predominant motor abnormality that is spasticity. Objective: The purpose of the present study was to compare the efficacy of oral baclofen and oral tizanidine in reducing spasticity in cerebral palsy patients. Methodology: This randomized controlled trial was conducted from January 2010 to December 2011 and it was carried out in the Out Patient Department (OPD) of Pediatrics at Dhaka Medical College Hospital (DMCH), Dhaka, Bangladesh and Center for Neurodevelopment and Autism in Children (CNAC) of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Results: A total number of 70 cerebral palsy children were recruited for this study of which 35 patients were in Tizanidine group and 35 patients were in baclofen group. Furthermore, 70 cerebral palsy children were taken as control who were treated with placebo. Tizanidine had superior efficacy in reducing tone in spastic cerebral palsy over baclofen measured by using Modified Ashworth scale in different time periods from AS score-3 to score-2 (p physician rating scale from AS score-3 to score-2 (crouch p Adverse effect was more in baclofen group. Conclusion: For reducing generalized spasticity with regards to muscle tone, joint angle and improvement in gait in cerebral palsy patients, tizanidine has superior efficacy and less adverse effects than baclofen.