Preclinical studies suggest that the GABA receptor is a potential target for treatment of substance use disorders. Baclofen (BLF), a prototypical GABA receptor agonist, is the only specific GABA receptor agonist available for application in clinical addiction treatment. The nucleus accumbens shell (AcbSh) is a key node in the circuit that controls reward-directed behavior. However, the relationship between GABA receptors in the AcbSh and memory reconsolidation was unclear. The aim of this study was to investigate the effect of intra-AcbSh injection of BLF on the reconsolidation of morphine reward memory. Male C57BL/6J mice were used to establish morphine conditioned place preference (CPP) model and carry out morphine reward memory retrieval and activation experiment. The effects of intra-AcbSh injection of BLF on morphine-induced CPP, reinstatement of CPP and locomotor activity were observed after environmental cues activating morphine reward memory. The results showed that intra-AcbSh injection of BLF (0.06 nmol/0.2 μL/side or 0.12 nmol/0.2 μL/side), rather than vehicle or BLF (0.01 nmol/0.2 μL/side), following morphine reward memory retrieval abolished morphine-induced CPP by disrupting its reconsolidation in mice. Moreover, this effect persisted for more than 14 days, which was not reversed by a morphine priming injection. Furthermore, intra-AcbSh injection of BLF without morphine reward memory retrieval had no effect on morphine-associated reward memory. Interestingly, administration of BLF into the AcbSh had no effect on the locomotor activity of mice during testing phase. Based on these results, we concluded that intra-AcbSh injection of BLF following morphine reward memory could erase morphine-induced CPP by disrupting its reconsolidation. Activating GABA receptor in AcbSh during drug memory reconsolidation may be a potential approach to prevent drug relapse.
Animals ; Baclofen ; administration & dosage ; Conditioning, Classical ; GABA-B Receptor Agonists ; administration & dosage ; Locomotion ; Male ; Memory ; Mice ; Mice, Inbred C57BL ; Morphine ; Nucleus Accumbens ; drug effects ; Opioid-Related Disorders ; Reward

Deep brain stimulation (DBS) in internal globus pallidus is considered to be a good option for controlling generalized dystonia in patients with this condition. In this relation, it is known that DBS has already been shown to have significant effects on primary dystonia, but is seen as controversial in secondary dystonia including cerebral palsy (CP). On the other hand, intrathecal baclofen (ITB) has been known to reduce spasticity and dystonia in patients who did not respond to oral medications or botulinum toxin treatment. Here, we report a patient with dystonic CP, who received the ITB pump implantation long after the DBS and who noted remarkable improvement in the 36-Item Short Form Health Survey, Dystonia Rating Scale, Modified Barthel Index, and visual analog scale scores for pain after an ITB pump implantation was used as compared with DBS. To our knowledge, the present case report is the first to demonstrate the effects of an ITB pump on reducing pain and dystonia and improving quality of life and satisfaction, compared with DBS in a patient with CP.
Baclofen ; Botulinum Toxins ; Cerebral Palsy ; Deep Brain Stimulation ; Dystonia ; Dystonic Disorders ; Globus Pallidus ; Hand ; Health Surveys ; Humans ; Muscle Spasticity ; Quality of Life ; Visual Analog Scale

OBJECTIVE: To investigate dosage changes in intrathecal baclofen during long-term treatment of patients with severe leg spasticity. METHODS: We performed a retrospective chart review of 49 patients treated with an intrathecal baclofen pump (ITB) because of severe leg spasticity, for a minimum of 7 years. Eight patients were excluded due to catheter/pump failure or factors aggravating spasticity. Of the remaining 41 patients, 19 had spinal cord injury (SCI) and 22 were diagnosed with multiple sclerosis (MS). Among the SCI patients, 15 had cervical and 4 thoracic SCI, with 7 patients showing the American Spinal Injury Association impairment scale (AIS) A and 12 patients with AIS B–D. The dose was regulated by discussion among the patients and their physicians, usually 4–10 times annually, to reduce leg spasticity and also avoid leg/trunk weakness. RESULTS: After 1 year patients on ITB needed a median dose of 168 mg/24 hr (range, 30–725 mg) for an optimal effect. After 7 to 10 years the dosage needed to reduce leg spasticity in the MS patients was significantly increased compared with the initial dose (mean 157%, n=22 and mean 194%, n=18). In contrast, the SCI patients needed only a modest increase (mean 113% and 121%). The difference between MS and SCI patients was significant (t-test p=0.006 and p=0.004). CONCLUSION: The increased dosage in MS patients compared with patients diagnosed with SCI probably reflects the progressive disease course. The need for a large dosage increase in patients with SCI suggests possible pump failure, triggering factors for spasticity or progressive spinal disease.
Baclofen ; Humans ; Infusions, Spinal ; Leg ; Multiple Sclerosis ; Muscle Spasticity ; Retrospective Studies ; Spinal Cord Injuries ; Spinal Cord ; Spinal Diseases ; Spinal Injuries

Hiccup is an intermittent, involuntary and erratic contraction of the diaphragm, immediately followed by a laryngeal closure. Persistent and intractable hiccups are rare but severe, keeping a person from doing daily activities; these can result in depression, fatigue, impaired sleep, dehydration, weight loss, malnutrition, and aspiration. Therefore, proper treatments are necessary. We present a case with intractable hiccup treated with an unusual treatment. A 61-year-old man presented with intractable hiccups, which started 6 years ago after subarachnoid and intraventricular hemorrhage. Conventional pharmacologic treatments including metoclopramide, gabapentin, and baclofen were unsuccessful. Cooperating with cardiothoracic surgeons, phrenic nerve clipping operation was done under intraoperative electrophysiologic monitoring. This method was successful that the symptoms were relieved. Reversible clipping done under intraoperative electrophysiologic monitoring can be a promising therapeutic method for persistent and intractable hiccups in patients with stroke.
Baclofen ; Dehydration ; Depression ; Diaphragm ; Electromyography ; Fatigue ; Hemorrhage ; Hiccup* ; Humans ; Malnutrition ; Methods ; Metoclopramide ; Middle Aged ; Phrenic Nerve* ; Stroke* ; Surgeons ; Weight Loss

Intrathecal baclofen (ITB) pump implantation can be used to control dystonia and severe pain associated with complex regional pain syndrome (CRPS) with or without a spinal cord stimulator (SCS). A 45-year-old female patient had gotten an SCS to control the pain of CRPS. However, she suffered from chronic intractable pain in her left ankle and foot despite paresthesia in the entire painful area because the effectiveness of the SCS gradually diminished over time. In a trial of intrathecal drug administration, baclofen was superior to morphine for pain relief, had fewer side effects, and was superior in terms of patient satisfaction. To achieve the greatest degree of pain relief from the ITB pump, the tip of the intrathecal catheter was carefully placed in relation to the SCS. Over a one-year follow-up period, the patient experienced mild pain without any adverse effects.
Ankle ; Baclofen* ; Catheters* ; Dystonia ; Female ; Follow-Up Studies ; Foot ; Humans ; Middle Aged ; Morphine ; Pain, Intractable ; Paresthesia ; Patient Satisfaction ; Spinal Cord Stimulation ; Spinal Cord*

OBJECTIVE: Baclofen is a promising treatment for alcohol use disorders (AUD), although its clinical response in humans is mixed. The present study aimed at investigating the impact of baclofen treatment on cue-induced brain activation pattern and its relationship with relapse outcomes. METHODS: Twenty-three inpatients with AUD underwent a functional magnetic resonance imaging cue-reactivity task before beginning medication with baclofen and 2 weeks later. Twelve additional inpatients with AUD, who did not receive any anticraving medications, formed the control group. All subjects were prospectively followed up for 90 days post-discharge or until lapse to first alcohol use. RESULTS: Whole-brain linear mixed effects analysis revealed a significant group-by-time interaction with greater activation of the bilateral dorsolateral pre-frontal cortex and right anterior cingulate cortex (ACC) following baclofen treatment in comparison with the control group. Further, cox regression analysis revealed that increased activation of ACC and deactivation of insular cortex (IC) was associated with longer time to first alcohol use only in the baclofen treatment group but not in the control group. CONCLUSION: This study provides preliminary evidence for the neural predictors of baclofen treatment response in AUD. Baclofen treatment in AUD was associated with changes in cue-reactivity at critical brain regions within the incentive-salience network. Importantly, baclofen treatment-related specific activation of regions involved in cognitive control (ACC) and deactivation of regions involved in reward anticipation (IC) prolonged the time to first alcohol drink.
Baclofen* ; Brain* ; Cerebral Cortex ; Gyrus Cinguli ; Humans ; Inpatients ; Magnetic Resonance Imaging* ; Prospective Studies ; Recurrence ; Reward

No abstract available.
Baclofen

BACKGROUND/AIMS: Neurologically impaired patients frequently suffer from gastrointestinal tract problems, such as gastroesophageal reflux disease (GERD). In this study, we aimed to define the risk factors for GERD in neurologically impaired children. METHODS: From May 2006 to March 2014, 101 neurologically impaired children who received 24-hour esophageal pH monitoring at Severance Children’s Hospital were enrolled in the study. The esophageal pH finding and the clinical characteristics of the patients were analyzed. RESULTS: The reflux index was higher in patients with abnormal electroencephalography (EEG) results than in those with normal EEG results (p=0.027). Mitochondrial disease was associated with a higher reflux index than were epileptic disorders or cerebral palsy (p=0.009). Patient gender, feeding method, scoliosis, tracheostomy, and baclofen use did not lead to statistical differences in reflux index. Age of onset of neurological impairment was inversely correlated with DeMeester score and reflux index. Age at the time of examination, the duration of the disease, and the number of antiepileptic drugs were not correlated with GER severity. CONCLUSIONS: Early-onset neurological impairment, abnormal EEG results, and mitochondrial disease are risk factors for severe GERD.
Age of Onset ; Anticonvulsants ; Baclofen ; Cerebral Palsy ; Child* ; Electroencephalography ; Esophageal pH Monitoring ; Feeding Methods ; Gastroesophageal Reflux* ; Gastrointestinal Tract ; Humans ; Hydrogen-Ion Concentration ; Mitochondrial Diseases ; Risk Factors* ; Scoliosis ; Tracheostomy

Baclofen is a gamma-aminobutyric acid type B receptor agonist used as an anti-craving agent for treatment of alcohol dependence. It has gained popularity in the recent times because it is well tolerated even in patients with hepatic impairments. Herein we are summarizing the latest literature about baclofen induced hypomania and are reporting a case of baclofen abuse because of its mood elevating property in a patient of alcohol dependence with comorbid major depressive disorder. Literature review and case study of a 36-year-old male with alcohol dependence with comorbid major depressive disorder was prescribed with tablet baclofen as an anti-craving agent along with antidepressant medicines. The patients who did not improve with conventional antidepressant therapy started feeling better in terms of his mood symptoms on taking tablet baclofen. Owing to the mood elevating property he started abusing baclofen. Despite its safety profile in hepatic impairment, one must be very cautious in prescribing baclofen because of its mood altering property which may account for its abuse potentiality.
Adult ; Alcoholism* ; Baclofen* ; Depressive Disorder, Major* ; Depressive Disorder, Treatment-Resistant ; gamma-Aminobutyric Acid ; Humans ; Male

INTRODUCTIONIntrathecal baclofen (ITB) therapy is a proven, effective treatment for disabling cortical spasticity. We describe the first local series of five patients with acquired brain injury (ABI) who received ITB and were followed up for 63.8 months.

METHODSA retrospective review of medical and rehabilitation records of patients who received ITB therapy was carried out. Data studied included baseline demographic and injury variables, implantation data, spasticity and function, ITB dosage over time and complications.

RESULTSFrom 2006 to 2010, a total of five patients received ITB therapy via implanted pumps about 39.4 months after ABI. Four out of five patients experienced significant reductions in their lower limb spasticity scores and improvements in global function and dependency. One patient had minor adverse events associated with baclofen-related sedation. The mean ITB dose at one year was 182.7 ± 65.6 mcg/day.

CONCLUSIONOur preliminary study showed encouraging long-term outcomes and safety for ITB therapy after ABI-related intractable spasticity. Individual ITB responses over time were variable, with gender differences. The outcomes experienced by our centre were comparable to those in the general ABI population, supporting the efficacy of ITB therapy for chronic disabling spasticity.

Baclofen ; administration & dosage ; Brain Injuries ; complications ; drug therapy ; Dose-Response Relationship, Drug ; Female ; Follow-Up Studies ; Humans ; Infusion Pumps, Implantable ; Injections, Spinal ; Male ; Muscle Relaxants, Central ; administration & dosage ; Muscle Spasticity ; diagnosis ; drug therapy ; etiology ; Retrospective Studies ; Severity of Illness Index ; Singapore ; epidemiology ; Tertiary Care Centers ; Treatment Outcome