OBJECTIVETo study the changes in plasma substance P (SP) and calcitonin gene-related peptide (CGRP) levels in children with acute asthma before and after gamma-aminobutyric acid (GABA) treatment.

METHODSSeventy-five children with asthma were randomly assigned to GABA treatment (n=36) and control groups (n=39). Both groups were given conventional treatment for asthma. Besides the conventional treatment, the treatment group was administered with oral GABA (25-30 mg/kg•d). Plasma content of SP and CGRP was measured using ELISA before treatment and after remission.

RESULTSThere were no significant differences in plasma content of SP and CGRP between the GABA treatment and control groups (P＞0.05) before treatment. Plasma content of SP and CGRP in the GABA treatment group was significantly lower than the control group (SP: 57±15 pg/mL vs 127±12 pg/mL; CGRP: 23±10 pg/mL vs 42±8 pg/mL) after remission (P<0.01). Plasma content of SP and CGRP after remission was significantly lower than before treatment (P<0.01) in both groups. There was a significantly positive correlation between plasma SP and CGRP content in asthmatic children (r=0.792, P<0.01).

CONCLUSIONSGABA can significantly decrease plasma levels of SP and CGRP in children suffering from acute asthma.

Asthma ; blood ; drug therapy ; Calcitonin Gene-Related Peptide ; blood ; Child ; Child, Preschool ; Female ; Humans ; Male ; Substance P ; blood ; gamma-Aminobutyric Acid ; pharmacology ; therapeutic use

Conditioned fear and its abnormal extinction are involved in the psychopathology of anxiety disorders, such as posttraumatic stress disorder (PTSD). Cognitive enhancing agents have been demonstrated to alter fear extinction in many animal research literatures. The present review has examined the pharmacological role of gamma-aminobutyric acid (GABA), glutamatergic, cholinergic, adrenergic, dopaminergic, and cannabinoid as well as compounds able to alter the epigenetic and neurotrophic mechanism in fear extinction, highlighting great hope for the future treatment of anxiety disorders with new agents based on the fear extinction.
Animals ; Anxiety Disorders ; drug therapy ; psychology ; Cannabinoids ; pharmacology ; therapeutic use ; Conditioning, Psychological ; drug effects ; Extinction, Psychological ; drug effects ; Fear ; drug effects ; psychology ; Humans ; Nootropic Agents ; pharmacology ; Stress Disorders, Post-Traumatic ; drug therapy ; psychology ; gamma-Aminobutyric Acid ; pharmacology ; therapeutic use

OBJECTIVETo explore the analgesia of oxymatrine (OMT) affecting high voltage-dependent calcium channels (HVDCCs) and GABA release under neuropathic pain condition.

METHODSTotally 66 C57BL/6 mice were randomly divided into the sham-operation group, the model group, and the OMT group, 22 in each group. Neuropathic pain models were established by partial sciatic nerve ligation (PSNL). Hind paw plantar mechanical response threshold (MWT) was measured by up-and-down method with Von-Frey filament. mRNA expression of HVDCCs in brains and spinal cords was detected with Real-time PCR and concentration of GABA was determined using ELISA kit.

RESULTSCompared with day 0, the left hind paw MWTwas decreased on day 7, 10, and 14 in the model group (P < 0.05). Compared with the sham-operation group, the left hind paw MWT was significantly reduced in the model group on day 7 (P < 0.05). The MWT of PSNL ipsilateral hind paw was decreased on day 7 before OMT administration, when compared with day 0 (P < 0.05), and increased after OMT administration (P < 0.05). Compared with the sham-operation group, mRNA levels of Cav1.2, Cav1.3, Cav2.1, and Cav2.3 in brain tissues were increased and those of Cav2.2 were decreased significantly in the model group (P < 0.05). In spinal cord tissues, mRNA levels of Cav1.2 and Cav1.3 were increased, but those of Cav2.1, Cav2.2, and Cav2. 3 were decreased significantly in the model group, when compared with those of the sham-operation group (P < 0.05). Compared with the model group, mRNA levels of Cavl.2, Cavl.3, Cav2.1, and Cav2. 3 in brain tissues were decreased, and those of Cav2.2 were increased significantly in the OMT group (P < 0.05). In spinal cord tissues of the OMT group, mRNA levels of Cav1.3 decreased and those of Cav2.1, Cav2.2, and Cav2.3 increased significantly with statistical difference, when compared with those of the model group (P < 0.05). Compared with the sham-operation group, GABA levels in brain tissues decreased in the model group (P < 0.05). Compared with the model group, GABA levels in brain tissues increased in the OMT group (P < 0.05). There was no statistical difference in GABA levels of spinal cord tissues among these groups (P > 0.05).

CONCLUSIONSOMT had analgesic effect on neuropathic pain, which might be probably related to HVDDCs. Cav2.2 might directly affect GABA release.

Alkaloids ; pharmacology ; therapeutic use ; Analgesia ; methods ; Animals ; Calcium ; Calcium Channels ; drug effects ; metabolism ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Neuralgia ; drug therapy ; Pain Management ; Quinolizines ; pharmacology ; therapeutic use ; Spinal Cord ; metabolism ; gamma-Aminobutyric Acid

We examined the possible anti-inflammatory mechanisms of gabapentin in the attenuation of neuropathic pain and the interaction between the anti-allodynic effects of gabapentin and interleukin-10 (IL-10) expression in a rat model of neuropathic pain. The anti-allodynic effect of intrathecal gabapentin was examined over a 7-day period. The anti-allodynic effects of IL-10 was measured, and the effects of anti-IL-10 antibody on the gabapentin were assessed. On day 7, the concentrations of pro-inflammatory cytokines and IL-10 were measured. Gabapentin produced an anti-allodynic effect over the 7-day period, reducing the expression of pro-inflammatory cytokines but increasing the expression of IL-10 (TNF-alpha, 316.0 +/- 69.7 pg/mL vs 88.8 +/- 24.4 pg/mL; IL-1beta, 1,212.9 +/- 104.5 vs 577.4 +/- 97.1 pg/mL; IL-6, 254.0 +/- 64.8 pg/mL vs 125.5 +/- 44.1 pg/mL; IL-10, 532.1 +/- 78.7 pg/mL vs 918.9 +/- 63.1 pg/mL). The suppressive effect of gabapentin on pro-inflammatory cytokine expression was partially blocked by the anti-IL-10 antibody. Expression of pro-inflammatory cytokines was significantly attenuated by daily injections of IL-10. The anti-allodynic effects of gabapentin may be caused by upregulation of IL-10 expression in the spinal cord, which leads to inhibition of the expression of pro-inflammatory cytokines in the spinal cords.
Amines/pharmacology/*therapeutic use ; Analgesics/pharmacology/*therapeutic use ; Animals ; Antibodies/immunology/pharmacology ; Behavior, Animal/drug effects ; Cyclohexanecarboxylic Acids/pharmacology/*therapeutic use ; Cytokines/*metabolism ; Disease Models, Animal ; Injections, Spinal ; Interleukin-10/genetics/immunology/*metabolism ; Male ; Neuralgia/*drug therapy/metabolism/pathology ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/biosynthesis/genetics/pharmacology ; Spinal Cord/metabolism ; Up-Regulation ; gamma-Aminobutyric Acid/pharmacology/*therapeutic use

INTRODUCTIONGabapentin has demonstrated efficacy in clinical trials as a pre-emptive analgesic and in acute postoperative pain management. However, our experience with the drug is still limited. The present study was conducted in order to evaluate the effect of gabapentin on reduction of postoperative pain in the first 24 hours after internal fixation of the tibia under spinal anaesthesia.

METHODSIn a double-blind, randomised controlled clinical trial, 64 American Society of Anesthesiologists Class I or II patients, who underwent internal fixation of the tibia, were administered 300 mg of gabapentin or a placebo two hours before surgery. The postoperative pain was assessed using Visual Analogue Scale two, 12 and 24 hours after surgery. The time from the end of surgery until the first bolus dose of morphine on demand (pain score > 4) and the total morphine requirement were recorded. Patients were also asked about the possible side effects of gabapentin.

RESULTSThe pain score was significantly lower in the gabapentin group at two hours post surgery (p-value is 0.004), while the scores at 12 and 24 hours post surgery were not significantly different between the two groups. No side effect of gabapentin was observed.

CONCLUSIONPre-emptive use of gabapentin 300 mg orally significantly decreases postoperative pain two hours after surgery.

Adult ; Amines ; pharmacology ; therapeutic use ; Anesthesia, Spinal ; methods ; Anesthesiology ; methods ; Cyclohexanecarboxylic Acids ; pharmacology ; therapeutic use ; Double-Blind Method ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Morphine ; therapeutic use ; Orthopedics ; methods ; Pain ; drug therapy ; Pain, Postoperative ; Placebos ; Tibia ; surgery ; Time Factors ; Treatment Outcome ; gamma-Aminobutyric Acid ; pharmacology ; therapeutic use