OBJECTIVE: Black sticky rice with giant embryo (BSRGE) contains high GABA content and affects alcohol-related indices among social drinkers, and alcohol intake and anxiety-related behavior of mice. However, it is unknown whether the intake of BSRGE affects GABAergic activity of brain directly. The purpose of this study is to elucidate the effect of oral administration of BSRGE on brain GABA concentrations compared with commercially available GABA compound and regular feeds. METHODS: Twenty-one male C57BL/6 mice were assigned to BSRGE, a regular feed (AIN-76) lacking GABA, and a regular feed containing GABA compound. After feeding freely for 48 h, the cortex and striatum were separated from the brain. An enzyme-linked immunosorbent assay was conducted to measure GABA and glutamate concentrations in mouse brain. RESULTS: The GABA concentration of the BSRGE group was higher than that of regular feed and GABA compound group (p<0.001). However, the GABA compound group showed no significant difference from the regular feed group (p=0.50). CONCLUSION: Intake of BSRGE containing high GABA content increased GABA concentrations in mouse brain compared with regular feed unlike GABA compound. The results of this study constitute an important basis for further investigations into the clinical applications of BSRGE.
Administration, Oral ; Animals ; Brain ; Embryonic Structures ; Enzyme-Linked Immunosorbent Assay ; gamma-Aminobutyric Acid ; Glutamic Acid ; Humans ; Male ; Mice

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

OBJECTIVETo study the clinical effects of gabapentin on the treatment of pruritus of scar resulting from deep partial-thickness burn.

METHODSA total of fifty-eight patients suffering from pruritus of scar after deep partial-thickness burn were hospitalized from January 2013 to January 2014. Patients were divided into placebo group (n =18, treated with oral vitamin C in the dose of 100 mg for 4 weeks, twice per day) , cetirizine group (n = 20, treated with oral cetirizine in the dose of 10 mg for 4 weeks, twice per day) , and gabapentin group (n = 20, treated with oral gabapentin in the dose of 300 mg for 4 weeks, twice per day) . Before treatment and on post treatment day (PTD) 3 and 28, the Visual Analog Scale (VAS) was used to assess the itching degree, and the mean scores were recorded. The remission rates of pruritus on PTD 3 and 28 were calculated. The adverse effects were observed during treatment. Data were processed with analysis of variance, q test, and chi-square test.

RESULTSCompared with that before treatment, the itching degree of patients with light, moderate, and severe itching in placebo group was not relieved after treatment; the itching degree of patients with moderate or severe itching in cetirizine group was alleviated after treatment, but not in patients with light itching; itching degree of all patients in gabapentin group was significantly relieved after treatment. There were no obvious differences in VAS scores among the 3 groups before treatment (F = 2.78, P > 0.05). On PTD 3 and 28, the VAS scores of patients in both gabapentin group [(2.3 ± 0.8) and (0.6 ± 0.3) points] and cetirizine group [(4.2 ± 1.7) and (2.8 ± 1.2) points] were lower than those in placebo group [(5.7 ± 2.0) and (5.7 ± 1.9) points, with q values from 6.70 to 7.75, P values below 0.05]. The VAS scores of patients in gabapentin group on PTD 3 and 28 were lower than those in cetirizine group (with q values respectively 6.30 and 6.90, P values below 0.05). The remission rates of pruritus of patients in gabapentin group on PTD 3 and 28 were respectively (66 ± 20)% and (91 ± 17)%, and they were higher than those in cetirizine group [(33 ± 8)% and (56 ± 14)%, with q values respectively 4.70 and 3.82, P values below 0.05]. The remission rate of pruritus of patients in placebo group on PTD 3 and 28 was 0, which was lower than that of the other 2 groups each (with q values from 3.94 to 6.76, P values below 0.05). During the course of treatment, 5 patients in gabapentin group suffered from adverse effects including mild-to-moderate drowsiness and dizziness, but they disappeared one week later. No adverse effects were observed in patients of the other two groups.

CONCLUSIONSFor patients with deep partial-thickness burn, gabapentin can effectively alleviate scar itching after wound healing with safety.

Amines ; administration & dosage ; therapeutic use ; Analgesics ; therapeutic use ; Ascorbic Acid ; administration & dosage ; Burns ; complications ; Cetirizine ; administration & dosage ; Cicatrix ; Cyclohexanecarboxylic Acids ; administration & dosage ; therapeutic use ; Humans ; Pruritus ; drug therapy ; Skin Transplantation ; Treatment Outcome ; Visual Analog Scale ; Wound Healing ; gamma-Aminobutyric Acid ; administration & dosage ; therapeutic use

This study was performed to investigate the sedative-hypnotic activity of gamma-aminobutyric acid (GABA)-enriched fermented marine organisms (FMO), including sea tangle (FST) and oyster (FO) by Lactobacillus brevis BJ20 (L. brevis BJ20). FST and FO were tested for their binding activity of the GABA(A)-benzodiazepine and 5-HT(2C) receptors, which are well-known molecular targets for sleep aids. We also measured the sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of FST and FO. In GABA(A) and 5-HT(2C) receptor binding assays, FST displayed an effective concentration-dependent binding affinity to GABA(A) receptor, similar to the binding affinity to 5-HT(2C) receptor. FO exhibited higher affinity to 5-HT(2C) receptor, compared with the GABA(A) receptor. The oral administration of FST and FO produced a dose-dependent decrease in sleep latency and increase in sleep duration in pentobarbital-induced hypnosis. The data demonstrate that FST and FO possess sedative-hypnotic activity possibly by modulating GABA(A) and 5-HT(2C) receptors. We propose that FST and FO might be effective agents for treatment of insomnia.
Administration, Oral ; Animals ; Aquatic Organisms* ; gamma-Aminobutyric Acid ; Hypnosis ; Lactobacillus brevis ; Mice ; Ostreidae ; Receptor, Serotonin, 5-HT2C ; Receptors, GABA-A ; Sleep Initiation and Maintenance Disorders

This study was investigated to know whether pachymic acid (PA), one of the predominant triterpenoids in Poria cocos (Hoelen) has the sedative-hypnotic effects, and underlying mechanisms are mediated via gamma-aminobutyric acid (GABA)-ergic systems. Oral administration of PA markedly suppressed locomotion activity in mice. This compound also prolonged sleeping time, and reduced sleep latency showing synergic effects with muscimol (0.2 mg/kg) in shortening sleep onset and enhancing sleep time induced by pentobarbital, both at the hypnotic (40 mg/kg) and sub-hypnotic (28 mg/kg) doses. Additionally, PA elevated intracellular chloride levels in hypothalamic primary cultured neuronal cells of rats. Moreover, Western blotting quantitative results showed that PA increased the amount of protein level expression of GAD65/67 over a broader range of doses. PA increased alpha- and beta-subunits protein levels, but decreased gamma-subunit protein levels in GABA(A) receptors. The present experiment provides evidence for the hypnotic effects as PA enhanced pentobarbital-induced sleeping behaviors via GABA(A)-ergic mechanisms in rodents. Taken together, it is proposed that PA may be useful for the treatment of sleep disturbed subjects with insomnia.
Administration, Oral ; Animals ; Blotting, Western ; Cocos ; gamma-Aminobutyric Acid ; Hypnotics and Sedatives ; Locomotion ; Mice* ; Muscimol ; Neurons ; Pentobarbital ; Poria ; Rats ; Receptors, GABA-A ; Rodentia ; Sleep Initiation and Maintenance Disorders

Fibromyalgia is a chronic pain syndrome of unknown etiology that is characterized by diffuse musculoskeletal pain, fatigue, sleep disturbance, memory disturbance, and exaggerated tenderness over particular paired locations. Fibromyalgia is found in 2% to 4% of the general population and more common in women, with symptoms usually appearing between 20 and 55 years of age. The diagnostic criteria for fibromyalgia syndrome established in 1990 by the American College of Rheumatology (ACR), includes widespread pain for at least 3 months and point tenderness upon the application of a 4 kg weight at 11 or more of the 18 characteristic tender points. The 2010 ACR preliminary diagnostic criteria have been developed, which are strongly correlated with the 1990 ACR criteria and provide an alternative approach to diagnosis. Patients with fibromyalgia syndrome have lower pain thresholds and experience an altered temporal summation to pain stimuli. The sensitization of pain perception occurs in the dorsal horn of patients with fibromyalgia. However, it is unknown whether sensitization is due to increased pain fiber facilitation, or decreased inhibition. Pregabalin is approved by the United States Food and Drug Administration for the management of fibromyalgia patients. Tricyclic antidepressants, cardiovascular exercise, cognitive behavioral therapy and patient education are also effective in reducing the pain experienced by fibromyalgia patients. This article provides an overview of fibromyalgia syndrome, which is currently thought to be partly responsible for chronic diffuse pain.
Animals ; Antidepressive Agents, Tricyclic ; Chronic Pain ; Cognitive Therapy ; Fatigue ; Female ; Fibromyalgia ; gamma-Aminobutyric Acid ; Horns ; Humans ; Memory ; Musculoskeletal Pain ; Pain Perception ; Pain Threshold ; Patient Education as Topic ; Rheumatology ; United States Food and Drug Administration ; Pregabalin

BACKGROUND: Gabapentin is a safe and well-tolerated anticonvulsant with a wide therapeutic index, and it is used for neuropathic pain. The aim of this study was to compare previous dosing methods with the administration of four different doses of gabapentin while maintaining the same maximum daily dose for the safe administration of high doses of the medication. METHODS: The subjects were outpatients with various neuropathic pain syndromes, with at least two of the following symptoms: allodynia, burning pain, shooting pain, or hyperalgesia. The TID group received equal doses of gabapentin 3 times per day, while the QID group received 4 different doses of gabapentin per day. The pain score, frequency of breakthrough pain (BTP), severity and the duration of pain, sleep disturbance due to nocturnal pain, and adverse effects were recorded each day. RESULTS: The average daily pain score and sleep disturbance were significantly reduced in the QID group between days 3 and 10 of the experiment. The adverse effects of the medication were also reduced in the QID group. However, the frequency of BTP and severity and duration of pain were not significantly different between two groups. CONCLUSIONS: Administration of 4 different doses of gabapentin during the initial titration in outpatients with neuropathic pain resulted in a significant reduction in awakening from breakthrough pain and a reduction in the adverse effects of the medication.
Ambulatory Care ; Amines ; Breakthrough Pain ; Burns ; Cyclohexanecarboxylic Acids ; Drug Administration Schedule ; gamma-Aminobutyric Acid ; Humans ; Hyperalgesia ; Neuralgia ; Outpatients

BACKGROUND: Pregabalin is an antiepileptic drug that is effective for treating postoperative pain, neuropathic pain, anxiety, and hemodynamic instability. The aim of this study was to investigate the effect of a single preoperative dose of pregabalin in patients with opioid-induced hyperalgesia (OIH). METHODS: Ninety ASA I-II patients undergoing laparoendoscopic single-site urologic surgery were randomly assigned to one of the following three groups that received either pregabalin or placebo 1 h before anesthesia and an intraoperative remifentanil infusion. Group plL received placebo and 0.05 microgram/kg/min remifentanil, group plH received placebo and 0.3 microgram/kg/min remifentanil, and group prH received 300 mg pregabalin plus 0.3 microgram/kg/min remifentanil. The primary endpoint was pain intensity upon movement 1, 6, 12, and 24 h after surgery. Secondary endpoints were the area of hyperalgesia and mechanical hyperalgesia threshold 24 h after surgery, time to first postoperative analgesic requirement, and cumulative postoperative volume of morphine administered via a patient-controlled analgesia (PCA) pump over 24 h. RESULTS: The time to first postoperative analgesic requirement in group plH was significantly shorter than that in group plL. The injected PCA volume was significantly greater in group plH than that in the other two groups. Postoperative pain intensity in group plH was significantly greater than that in the other two groups at 6, 12, and 24 h after surgery. The mechanical hyperalgesia threshold and the area of hyperalgesia around the surgical incision 24 h after surgery in group plH differed significantly from those in the other two groups, which were not significantly different. Adverse effects were comparable among groups. CONCLUSIONS: High-dose remifentanil induced hyperalgesia, including increased pain intensity, increased area of hyperalgesia, and decreased mechanical hyperalgesia threshold. These effects were attenuated by oral administration of a single preoperative dose of pregabalin (300 mg) in patients undergoing laparo-endoscopic single-site urologic surgery.
Administration, Oral ; Analgesia, Patient-Controlled ; Anesthesia ; Anxiety ; gamma-Aminobutyric Acid ; Hemodynamics ; Humans ; Hyperalgesia ; Morphine ; Neuralgia ; Pain, Postoperative ; Passive Cutaneous Anaphylaxis ; Piperidines ; Pregabalin

PURPOSE: Osteoarthritic pain is largely considered to be inflammatory pain. Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis (OA) in which the subchondral bone junction is destroyed, and this induces neuropathic pain (NP). Pregabalin was developed as a pain killer for NP; however, there are no reports on pregabalin use in OA patients. The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients. MATERIALS AND METHODS: Eighty-nine knee OA patients were evaluated in this randomized prospective study. Patients were divided into meloxicam, pregabalin, and meloxicam+pregabalin groups. Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain scales among groups were compared using a Kruskal-Wallis test. RESULTS: Before drug application, there was no significant difference in VAS and WOMAC scores among the three groups (p>0.05). Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1, 2, and 4 weeks, and WOMAC score at 4 weeks, compared with the other groups (p<0.05). No significant pain relief was seen in the meloxicam only group in VAS during 4 weeks and WOMAC score at 4 weeks compared with the pregabalin only group (p>0.05). CONCLUSION: Meloxicam+pregabalin was effective for pain in OA patients. This finding suggests that OA pain is a combination of inflammatory and NP.
Aged ; Aged, 80 and over ; Drug Therapy, Combination/adverse effects ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee/*drug therapy ; Pain Measurement ; Thiazines/administration & dosage/adverse effects/*therapeutic use ; Thiazoles/administration & dosage/adverse effects/*therapeutic use ; gamma-Aminobutyric Acid/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use

BACKGROUND: The primary site of action of pregabalin, i.e. the alpha-2-delta subunit of the voltage-dependent calcium channel, is located at the dorsal root ganglion and dorsal horn of the spinal cord. Therefore, the epidural administration of pregabalin could have advantages over oral administration. However, the possibility of its neurotoxicity should be excluded before any attempt at epidural administration. We evaluated the neuronal safety of epidurally-administered pregabalin by observing the sensory/motor changes and examining the histopathology of spinal cord in rats. METHODS: Sixty rats of 180-230 g were divided into three groups; 3 mg of pregabalin dissolved in 0.3 ml saline (group P, n = 20), 0.3 ml 40% alcohol (group A, n = 20), or 0.3 ml normal saline (group N, n = 20) was administered epidurally to the rats in each group. Pinch-toe test, motor function evaluation, and histopathologic examination of vacuolation, chromatolysis, meningeal inflammation, and neuritis were performed at the 1st, 3rd, 7th, and 21st day after each epidural administration. RESULTS: All rats enrolled in group P, like those in group N, showed neither sensory/motor dysfunction nor any histopathological abnormality over the 3-week observation period. In contrast, in group A, 80% of the rats showed abnormal response to the pinch-toe test and all rats showed decreased motor function during the entire evaluation period. In addition, all histopathologic findings of neurotoxicity were observed exclusively in group A. CONCLUSIONS: The epidurally administered pregabalin (about 15 mg/kg) did not cause any neurotoxic evidence, in terms of both sensory/motor function evaluation and histopathological examination in rats.
Administration, Oral ; Animals ; Calcium Channels ; gamma-Aminobutyric Acid ; Ganglia, Spinal ; Horns ; Inflammation ; Injections, Epidural ; Neuritis ; Neurons ; Rats ; Spinal Cord ; Pregabalin