Only Early Intervention with Gamma-Aminobutyric Acid Cell Therapy Is Able to Reverse Neuropathic Pain After Partial Nerve Injury

2001 ◽  
Vol 18 (4) ◽  
pp. 471-477 ◽  
Author(s):  
Leigh Ann Stubley ◽  
Miguel A. Martinez ◽  
Shaffiat Karmally ◽  
Tomas Lopez ◽  
Pedro Cejas ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Early Intervention ◽  
Cell Therapy ◽  
Nerve Injury ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid

scholarly journals The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain

1999 ◽  
Vol 57 (3B) ◽  
pp. 753-760 ◽  
Author(s):  
TEREZINHA DE JESUS T. SANTOS ◽  
CARLOS M. DE CASTRO-COSTA ◽  
SÍLVIO D. A. GIFFONI ◽  
FRANKLIN J. C. SANTOS ◽  
RODRIGO S. N. RAMOS ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Aminobutyric Acid ◽  
Thermal Stimulus ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Analgesic Effects ◽  
Nociceptive Stimulus ◽  
Dose Dependent

Baclofen (beta-p-chlorophenyl-GABA) has been used in humans to treat spasticity, as well as trigeminal neuralgia. Since GABA (gamma-aminobutyric acid) has been implicated in inhibitory and analgesic effects in the nervous system, it was of interest to study the effect of baclofen in experimental neuropathic pain. With this purpose, experiments were carried out in 17 neuropathic rats with constrictive sciatic injury, as described by Bennet and Xie (1988), taking as pain parameters scratching behaviour and the latency to the thermal nociceptive stimulus. The results showed that baclofen induces, in a dose-dependent manner, significant decrease (p < 0.05) of scratching behaviour and significant increase (p < 0.05) of the latency to the nociceptive thermal stimulus. The absence of antagonism of naloxone suggested a non-participation of an opioid-mediated mechanism in this analgesic effect of baclofen on experimental neuropathic pain.

Neurosteroid Allopregnanolone Suppresses Median Nerve Injury–induced Mechanical Hypersensitivity and Glial Extracellular Signal–regulated Kinase Activation through γ-Aminobutyric Acid Type A Receptor Modulation in the Rat Cuneate Nucleus

2016 ◽  
Vol 125 (6) ◽  
pp. 1202-1218 ◽  
Author(s):  
Chun-Ta Huang ◽  
Seu-Hwa Chen ◽  
June-Horng Lue ◽  
Chi-Fen Chang ◽  
Wen-Hsin Wen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Median Nerve ◽  
Nerve Injury ◽  
Type A ◽  
Aminobutyric Acid ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Acid Type ◽  
Extracellular Signal ◽  
Median Nerve Injury

Abstract Background Mechanisms underlying neuropathic pain relief by the neurosteroid allopregnanolone remain uncertain. We investigated if allopregnanolone attenuates glial extracellular signal-regulated kinase (ERK) activation in the cuneate nucleus (CN) concomitant with neuropathic pain relief in median nerve chronic constriction injury (CCI) model rats. Methods We examined the time course and cellular localization of phosphorylated ERK (p-ERK) in CN after CCI. We subsequently employed microinjection of a mitogen-activated protein kinase kinase (ERK kinase) inhibitor, PD98059, to clarify the role of ERK phosphorylation in neuropathic pain development. Furthermore, we explored the effects of allopregnanolone (by mouth), intra-CN microinjection of γ-aminobutyric acid type A receptor antagonist (bicuculline) or γ-aminobutyric acid type B receptor antagonist (phaclofen) plus allopregnanolone, and allopregnanolone synthesis inhibitor (medroxyprogesterone; subcutaneous) on ERK activation and CCI-induced behavioral hypersensitivity. Results At 7 days post-CCI, p-ERK levels in ipsilateral CN were significantly increased and reached a peak. PD98059 microinjection into the CN 1 day after CCI dose-dependently attenuated injury-induced behavioral hypersensitivity (withdrawal threshold [mean ± SD], 7.4 ± 1.1, 8.7 ± 1.0, and 10.3 ± 0.8 g for 2.0, 2.5, and 3.0 mM PD98059, respectively, at 7 days post-CCI; n = 6 for each dose). Double immunofluorescence showed that p-ERK was localized to both astrocytes and microglia. Allopregnanolone significantly diminished CN p-ERK levels, glial activation, proinflammatory cytokines, and behavioral hypersensitivity after CCI. Bicuculline, but not phaclofen, blocked all effects of allopregnanolone. Medroxyprogesterone treatment reduced endogenous CN allopregnanolone and exacerbated nerve injury-induced neuropathic pain. Conclusions Median nerve injury-induced CN glial ERK activation modulated the development of behavioral hypersensitivity. Allopregnanolone attenuated glial ERK activation and neuropathic pain via γ-aminobutyric acid type A receptors. Reduced endogenous CN allopregnanolone after medroxyprogesterone administration rendered rats more susceptible to CCI-induced neuropathy.

Drug Repositioning: Antimalarial Activities of GABA Analogs in Mice Infected with Plasmodium berghei

2020 ◽  
Vol 20 (2) ◽  
pp. 110-121
Author(s):  
Akeem A. Ayankunle ◽  
Olayemi K. Wakeel ◽  
Oyetunji T. Kolawole ◽  
Adesola O. Oyekale ◽  
Olusola Ojurongbe ◽  
...  
Keyword(s):  
Thin Films ◽  
Neuropathic Pain ◽  
Plasmodium Berghei ◽  
Post Infection ◽  
Drug Repositioning ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Treatment Of Epilepsy ◽  
Development Of Resistance ◽  
Almost All

Background: Drug repositioning is becoming popular due to the development of resistance to almost all the recommended antimalarials. Pregabalin and gabapentin are chemical analogs of gamma- aminobutyric acid (GABA) approved for the treatment of epilepsy and neuropathic pain. Objective: This study investigates acute toxicities and antimalarial activities of pregabalin and gabapentin in the murine malarial model. Methods: Acute toxicities were assessed using the method of Lorke, while curative activities were assessed by the administration of serial doses of pregabalin and gabapentin to Plasmodium berghei infected mice. Pregabalin was further investigated for its prophylactic activity, and curative potential when combined with either artesunate or amodiaquine. All drugs were freshly prepared and administered orally. Thin films were collected, stained, and observed under the microscope for the estimation of parasitemia and calculation of percentage chemoinhibition or chemoprevention. In pregabalin –artesunate or -amodiaquine combination aspect of this study, survival day post-infection (SDPI) was recorded, while parasitemia was re-estimated for animals that survived till day 28. Results: The oral LD50 of gabapentin, as well as pregabalin, was >5,000 mg/kg. Gabapentin at 100 and 200 mg/Kg demonstrated 35.64% and -12.78% chemoinhibition, respectively, while pregabalin demonstrated 75.60% and 100.00% chemoinhibition at doses of 12.5 and 25 mg/Kg, respectively. Moreover, pregabalin at individual doses of 25, 50 mg/Kg, and in combination with either artesunate or amodiaquine demonstrated 100.00% chemoinhibition. In its prophylactic study, pregabalin was found to be 100% chemopreventive at individual doses of 12.5 and 25 mg/Kg. Conclusion: Both GABA analogs have antimalarial properties, but pregabalin proved to be more efficacious.

scholarly journals Pregabalin abuse and toxicity and related factors

2021 ◽  
Vol 9 (1) ◽  
pp. 34-42
Author(s):  
Walla Alelwani ◽  
◽  
Abrar Alkhazindar ◽  
Basmah Alqumaysh ◽  
Dina Kutbi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Liver Enzymes ◽  
Liver Toxicity ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Structural Analogue ◽  
Related Factors ◽  
Abrupt Discontinuation ◽  
History Of

Pregabalin is one of a group of gabapentinoids approved by the Food and Drug Administration (FDA) in 2004. It is a capsule medication taken by mouth that is used for the treatment of neuropathic pain. It is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA), and it appears to have a spectrum of benefits and harms similar to those of other adjuvant analgesics used to treat neuropathic pain. The most common side effects mentioned in peripheral neuropathy studies are dizziness and somnolence. Pregabalin could cause liver toxicity by increasing the levels of liver enzymes. It can potentially cause vasodilatation and fluid retention in the heart and blood vessels. It may also lead to addiction. The use of Pregabalin is common among patients with a history of substance abuse and psychoactive drug dependence, as euphoria is one of its main side effects. However, abrupt discontinuation from using Pregabalin may cause nausea, insomnia, or headache. The present review evaluates the significant impact of Pregabalin toxicity on liver and heart in patients and misusers. Keywords: Pregabalin, liver toxicity, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), heart failure, addiction.

The Role of Ventral Tegmental Area Gamma-Aminobutyric Acid in Chronic Neuropathic Pain after Spinal Cord Injury in Rats

2018 ◽  
Vol 35 (15) ◽  
pp. 1755-1764 ◽  
Author(s):  
Moon Yi Ko ◽  
Eun Young Jang ◽  
June Yeon Lee ◽  
Soo Phil Kim ◽  
Sung Hun Whang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Ventral Tegmental Area ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Chronic Neuropathic Pain ◽  
Cord Injury ◽  
Ventral Tegmental

The Spinal Antinociceptive Effect of Nocistatin in Neuropathic Rats Is Blocked by D-Serine

2004 ◽  
Vol 101 (3) ◽  
pp. 753-758 ◽  
Author(s):  
Uta Muth-Selbach ◽  
Eva Dybek ◽  
Katrin Kollosche ◽  
Jens-Ulrich Stegmann ◽  
Holger Holthusen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Antinociceptive Effect ◽  
Receptor Activation ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Antinociceptive Action ◽  
Glycine Release ◽  
Aspartate Receptor ◽  
Nociceptive Responses ◽  
High Doses

Background The neuropeptide nocistatin (NST) has been implicated in the modulation of nociceptive responses in the spinal cord. Depending on the dose, both pronociceptive and antinociceptive effects have repeatedly been reported. The pronociceptive effect is most likely attributable to inhibition of synaptic glycine and gamma-aminobutyric acid release and a subsequent reduction in the activation of inhibitory glycine and gamma-aminobutyric acid receptors, but the mechanisms of its antinociceptive action have hitherto remained elusive. It has recently been demonstrated that synaptically released glycine contributes to N-methyl-D-aspartate receptor activation. The authors therefore investigated whether a reduction in glycine release might also account for the antinociceptive action of NST in neuropathic rats. Methods The authors analyzed the effects of spinally applied NST in the chronic constriction injury model of neuropathic pain. NST was injected intrathecally from nanomolar to picomolar doses and its effects on thermal paw withdrawal latencies were monitored. Furthermore, we tested whether D-serine (100 microg per rat), a full agonist at the glycine binding site of the N-methyl-D-aspartate receptor, would interfere with the effects of NST. Results At high doses (10 nmol/rat), intrathecally injected NST was pronociceptive, whereas lower doses (1 pmol/rat) elicited antinociception. The antinociceptive, but not the pronociceptive, action was occluded by intrathecal pretreatment with D-serine. L-serine, which does not bind to N-methyl-D-aspartate receptors, affected neither the pronociceptive nor the antinociceptive effect. Conclusions These results demonstrate that NST produces a biphasic dose-dependent effect on neuropathic pain. The spinal antinociception by NST is most likely attributable to inhibition of glycine-dependent N-methyl-D-aspartate receptor activation.

Purification of Antihemophilic Factor (Factor VIII) by Amino Acid Precipitation*

1964 ◽  
Vol 11 (01) ◽  
pp. 064-074 ◽  
Author(s):  
Robert H Wagner ◽  
William D McLester ◽  
Marion Smith ◽  
K. M Brinkhous
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Factor Viii ◽  
Plasma Protein ◽  
Acid Precipitation ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Specific Procedure ◽  
Beta Alanine ◽  
Antihemophilic Factor

Summary1. The use of several amino acids, glycine, alpha-aminobutyric acid, alanine, beta-alanine, and gamma-aminobutyric acid, as plasma protein precipitants is described.2. A specific procedure is detailed for the preparation of canine antihemophilic factor (AHF, Factor VIII) in which glycine, beta-alanine, and gammaaminobutyric acid serve as the protein precipitants.3. Preliminary results are reported for the precipitation of bovine and human AHF with amino acids.

A Simple Method for Preparing Fibrinogen

1966 ◽  
Vol 16 (01/02) ◽  
pp. 198-206 ◽  
Author(s):  
W Straughn ◽  
R. H Wagner
Keyword(s):  
Barium Sulfate ◽  
Caproic Acid ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Human Fibrinogen ◽  
Simple Method ◽  
High Yields ◽  
Marked Stability

SummaryA simple new procedure is reported for the isolation of canine, bovine, porcine, and human fibrinogen. Two molar β-alanine is used to precipitate fibrinogen from barium sulfate adsorbed plasma. The procedure is characterized by dependability and high yields. The material is 95% to 98% clottable protein but still contains impurities such as plasminogen and fibrin-stabilizing factor. Plasminogen may be removed by adsorption with charcoal. The fibrinogen preparations exhibit marked stability to freezing, lyophilization, and dialysis. Epsilon-amino-n-caproic acid and gamma-aminobutyric acid which were also studied have the property of precipitating proteins from plasma but lack the specificity for fibrinogen found with β-alanine.

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