Aged ; Baclofen ; administration & dosage ; pharmacology ; therapeutic use ; Hiccup ; drug therapy ; Humans ; Male ; Muscle Relaxants, Central ; administration & dosage ; pharmacology ; therapeutic use ; Neoplasms ; surgery ; Young Adult

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

BACKGROUND: Baclofen is a gamma-aminobutyric acid B-receptor agonist, which is usually used for patients with spasticity or patients with nerve injury inducing both spasticity and neuropathic pain. Both oral administration and intrathecal injection via a continuous infusion pump are common treatment methods. The aim of this study was to evaluate the effectiveness of a series of three individual injections of intrathecal baclofen for neuropathic pain without spasticity. METHODS: Thirty-one patients with neuropathic pain were treated with a series of three monthly individual injections of intrathecal baclofen without pump implantation A dose of 50 µg of baclofen was used. 10-cm visual analog scale (VAS) scores of spontaneous pain, allodynia, and hyperalgesia were recorded a week after each injection. Vital signs were monitored to detect any hemodynamic changes, and a myelogram was performed to detect any undesirable cerebrospinal fluid leakage. All patients were hospitalized for at least one day following each injection for close observation and to control any adverse effects. RESULTS: VAS scores of spontaneous pain, allodynia, and hyperalgesia decreased significantly (P < 0.001). The major complications were general weakness, sleepiness, and urinary retention; most of these resolved within one day without any further serious symptoms. CONCLUSIONS: A series of three individual intrathecal baclofen injections was effective for those patients who suffered from neuropathic pain without spasticity or dystonia; no serious complications were observed. However, the average satisfaction score recorded for spontaneous pain was lower than those for allodynia and hyperalgesia.
Administration, Oral ; Baclofen* ; Cerebrospinal Fluid Leak ; Dystonia ; gamma-Aminobutyric Acid ; Hemodynamics ; Humans ; Hyperalgesia ; Infusion Pumps ; Injections, Spinal ; Muscle Spasticity ; Neuralgia* ; Urinary Retention ; Visual Analog Scale ; Vital Signs

Glycine and gamma-aminobutyric acid (GABA) are localized and released by the same interneurons in the spinal cord. Although the effects of glycine and GABA on analgesia are well known, little is known about the effect of GABA in strychnine-induced hyperalgesia. To investigate the effect of GABA and the role of the glycine receptor in thermal hyperalgesia, we designed an experiment involving the injection of muscimol (a GABAA receptor agonist), baclofen (a GABAB receptor agonist) or glycine with strychnine (strychnine sensitive glycine receptor antagonist). Glycine, muscimol, or baclofen with strychnine was injected into the cisterna magna or lumbar subarachnoidal spaces of mice. The effects of treatment on strychnine-induced heat hyperalgesia were observed using the pain threshold index via the hot plate test. The dosages of experimental drugs and strychnine we chose had no effects on motor behavior in conscious mice. Intracisternal or intrathecal administration of strychnine produced thermal hyperalgesia in mice. Glycine antagonize the effects of strychnine, whereas, muscimol or baclofen does not. Our results indicate that glycine has anti-thermal hyperalgesic properties in vivo; and GABA receptor agonists may lack the binding abilities of glycine receptor antagonists with their sites in the central nervous system.
Animals ; Baclofen/*administration & dosage/pharmacology ; Drug Delivery Systems ; GABA Agonists/administration & dosage/pharmacology ; GABA Antagonists/administration & dosage/pharmacology ; Glycine/*administration & dosage/pharmacology ; Hot Temperature ; Hyperalgesia/chemically induced/*drug therapy ; Injections, Spinal ; Male ; Mice ; Mice, Inbred ICR ; Muscimol/*administration & dosage/pharmacology ; Pain Threshold ; Random Allocation ; Strychnine ; gamma-Aminobutyric Acid/metabolism

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