PURPOSE: Levodopa is the most effective anti-Parkinsonian agent. It has also been known to exhibit analgesic properties in laboratory and clinical settings. However, studies evaluating its effects on neuropathic pain are limited. The aim of the present study was to examine the anti-allodynic effects of levodopa in neuropathic rats. MATERIALS AND METHODS: Sprague-Dawley male rats underwent the surgical procedure for L5 and L6 spinal nerves ligation. Sixty neuropathic rats were randomly divided into 6 groups for the oral administration of distilled water and levodopa at 10, 30, 50, 70, and 100 mg/kg, respectively. We co-administered carbidopa with levodopa to prevent peripheral synthesis of dopamine from levodopa, and observed tactile, cold, and heat allodynia pre-administration, and at 15, 30, 60, 90, 120, 150, 180, and 240 min after drug administration. We also measured locomotor function of neuropathic rats using rotarod test to examine whether levodopa caused side effects or not. RESULTS: Distilled water group didn't show any difference in all allodynia. For the levodopa groups (10-100 mg/kg), tactile and heat withdrawal thresholds were increased, and cold withdrawal frequency was decreased dose-dependently (p<0.01). In addition, levodopa induced biphasic analgesia. Different dosage of levodopa did not impact on the rotarod time (p>0.05). CONCLUSION: Levodopa reversed tactile, cold and heat allodynia in neuropathic rat without any side effects.
Animals ; Carbidopa/administration & dosage/adverse effects/therapeutic use ; Dopamine Agents/administration & dosage/adverse effects/*therapeutic use ; Hyperalgesia/*drug therapy ; Levodopa/administration & dosage/adverse effects/*therapeutic use ; Male ; Neuralgia/*drug therapy ; Rats ; Rats, Sprague-Dawley ; Rotarod Performance Test

Recently it was shown that single nucleotide polymorphisms (SNPs) can explain individual variation because of the small changes of the gene expression level and that the 50% decreased expression of an allele might even lead to predisposition to cancer. In this study, we found that a decreased expression of an allele might cause predisposition to genetic disease. Dopa responsive dystonia (DRD) is a dominant disease caused by mutations in GCH1 gene. The sequence analysis of the GCH1 in a patient with typical DRD symptoms revealed two novel missense mutations instead of a single dominant mutation. Family members with either of the mutations did not have any symptoms of DRD. The expression level of a R198W mutant allele decreased to about 50%, suggesting that modestly decreased expression caused by an SNP should lead to predisposition of a genetic disease in susceptible individuals.
Child ; Clubfoot/genetics ; Dopamine/deficiency ; Dystonic Disorders/drug therapy/enzymology/*genetics/physiopathology ; GTP Cyclohydrolase/*genetics/metabolism ; Genes, Recessive ; *Genetic Predisposition to Disease ; Humans ; Levodopa/administration & dosage ; Male ; Mutation, Missense ; Pedigree ; Polymorphism, Genetic

PURPOSE: To evaluate the effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on levodopa-induced peakdose dyskinesia in patients with Parkinson's disease (PD). MATERIALS AND METHODS: A retrospective review was conducted on patients who underwent STN DBS for PD from May 2000 to July 2012. Only patients with levodopa-induced dyskinesia prior to surgery and more than 1 year of available follow-up data after DBS were included. The outcome measures included the dyskinesia subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV (items 32 to 34 of UPDRS part IV) and the levodopa equivalent daily dose (LEDD). The patients were divided into two groups based on preoperative to postoperative LEDD change at 12 months after the surgery: Group 1, LEDD decrease >15%; Group 2, all other patients. Group 2 was further divided by the location of DBS leads. RESULTS: Of the 100 patients enrolled, 67 were in Group 1, while those remaining were in Group 2. Twelve months after STN DBS, Groups 1 and 2 showed improvements of 61.90% and 57.14%, respectively, in the dyskinesia subscore. Group 1 was more likely to experience dyskinesia suppression; however, the association between the groups and dyskinesia suppression was not statistically significant (p=0.619). In Group 2, dyskinesia was significantly decreased by stimulation of the area above the STN in 18 patients compared to stimulation of the STN in 15 patients (p=0.048). CONCLUSION: Levodopa-induced dyskinesia is attenuated by STN DBS without reducing the levodopa dosage.
Aged ; Aged, 80 and over ; Antiparkinson Agents/administration & dosage/*adverse effects ; *Deep Brain Stimulation ; Dyskinesia, Drug-Induced/*therapy ; Female ; Humans ; Levodopa/administration & dosage/*adverse effects ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Parkinson Disease/*drug therapy ; Postoperative Period ; Retrospective Studies ; Subthalamic Nucleus ; Treatment Outcome

OBJECTIVETo analyze the clinical characteristics of the patient with tyrosine hydroxylase deficiency, and investigate it's molecular mechanism.

METHODThe clinical characteristics of a patient with tyrosine hydroxylase deficiency were summarized and analyzed, his and his family's peripheral blood specimens were collected after informed consent was signed. All exons and the intron-exon boundaries of guanosine triphosphate hydroxylase I gene, tyrosine hydroxylase gene and sepiapterin reductase gene were examined by DNA-PCR, bi-directional sequencing.

RESULTThe patient was a 3-year-old boy, presented with unexplained dystonia for 3 years, without significant impairment of intelligence. Physical examination showed limb muscle strength grade V, rigidity of extremities, hypertonicity, brisk deep tendon reflexes in limbs, without obvious abnormalities in auxiliary examination, such as brain MRI, hepatic biochemical panel, creatine kinase, and ceruloplasmin. He dramatically responded to small doses of levodopa in the follow-up for half a year. A homozygous missense change in exon 5 of TH gene, c.605G > A (p.R202H), which was a known pathogenic mutation, was found in the patient. His parents were heterozygous for the R202H mutation.

CONCLUSIONThe age of onset in tyrosine hydroxylase deficiency patients is usually within the first year of life. Unexplained dystonia and hypokinesia were the main clinical features of tyrosine hydroxylase deficiency. The dopa-responsive effects for some patients are so obvious that we should strengthen awareness of the disease. TH gene c.605G > A (p.R202H) may be a common type of causative mutations for the mild form at home and abroad.

Brain ; metabolism ; pathology ; Catecholamines ; biosynthesis ; Child, Preschool ; DNA ; genetics ; DNA Mutational Analysis ; Dopamine Agents ; administration & dosage ; therapeutic use ; Dystonic Disorders ; drug therapy ; genetics ; metabolism ; Homozygote ; Humans ; Hypokinesia ; drug therapy ; genetics ; metabolism ; Levodopa ; administration & dosage ; therapeutic use ; Male ; Muscle Rigidity ; drug therapy ; genetics ; metabolism ; Mutation, Missense ; Polymerase Chain Reaction ; Tyrosine 3-Monooxygenase ; deficiency ; genetics ; metabolism

OBJECTIVETo observe the effects of tetramethylpyrazine (TMP) on brain oxidative damage induced by intracerebral perfusion of levodopa (L-DOPA) in rats with Parkinson's disease (PD).

METHODSPD model rats were induced by intracerebral injection of 6-hydroxyl dopamine (6-OHDA) and perfused in brain with L-DOPA using microdialysis technique. Changes in levels of 2,3-dihydroxy benzyl acid (2.3-DHBA) and 2,5-dihydroxy benzyl acid (2,5-DHBA) in striatum of rats, formed by extracellular hydroxyl radical from salicylic acid capturing, were dynamically observed at various time points by HPLC-ED.

RESULTSAfter treatment with L-DOPA, 2,3-DHBA and 2,5-DHBA in the model group showed significantly higher levels at 6 and 7 time points as compared with those in the sham-operated group at the corresponding time points (P <0.05 or P< 0.01), while these abnormal elevations were significantly inhibited in the TMP treated groups, either in large or small dose (P<0.05 or P<0.01).

CONCLUSIONTMP could reduce the L-DOPA induced brain oxidative damage in PD rats.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Catechols ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Corpus Striatum ; drug effects ; metabolism ; pathology ; Hydroxybenzoates ; Levodopa ; administration & dosage ; Male ; Microdialysis ; Oxidative Stress ; drug effects ; Oxidopamine ; Parkinson Disease, Secondary ; chemically induced ; drug therapy ; metabolism ; Pyrazines ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley