Objective： To evaluate the analgesic efficacy of controlled-release （CR） oxycodone and gabapentin in malignant neuropathic pain （NP）. Methods： Patients with malignant NP were enrolled and baseline pain intensi...Objective： To evaluate the analgesic efficacy of controlled-release （CR） oxycodone and gabapentin in malignant neuropathic pain （NP）. Methods： Patients with malignant NP were enrolled and baseline pain intensity （PI） was recorded. They initially took one week CR oxycodone and were allocated to two different groups at day 8 by reevaluated PI. Patients with mild pain went to CR oxycodone mono-therapy group （OO group） and took another two weeks CR oxycodone. Others went to （CR oxycodone combined gabapentin group （OG group） and received additional gabapentin. Daily doses and side effects were recorded. Results： Fifty-eight （92.06%） of the 63 enrolled patients completed the initial week＇s therapy. Twenty-two （37.93%） went to OO group and PI significantly reduced at day 15 （2.00 vs. 2.62, P=0.004）, but not improved at day 22 （1.90 vs. 2.00, P=0.54）. Thirty-six （62.07%） patients went to OG group and PI was significantly reduced at day 15 （4,47 vs. 2.94, P〈0.001）, but not improved at day 22 （2.94 vs. 2.75, P=0.136）. Mean daily dose （MDD） of CR oxycodone at day 8 was 62.64 mg. It was significantly increased at days 15 and 22 （71.43 mg vs. 62.64 rag, P=0.021; 81.90 mg vs. 71.43 mg, P=0.004） in OO group. MDD of gabapentin was significantly increased at day 22 compared to day 15 （862.50 mg vs. 993.75 mg, P〈0.001）. Constipation was occurred in 13.64% of the patients in OO group and 14.26 % in OG group. Conclusion： Malignant NP may be well controlled by oxycodone mono-therapy. Early combination with gabapentin is sensible when pain is not satisfactory relieved by oxycodone alone. The side effects of them are manageable.展开更多
Adolescent alcohol abuse is a substantive public health problem that has been the subject of intensive study in recent years.Despite reports of a wide range of effects of adolescent intermittent ethanol(AIE)exposure o...Adolescent alcohol abuse is a substantive public health problem that has been the subject of intensive study in recent years.Despite reports of a wide range of effects of adolescent intermittent ethanol(AIE)exposure on brain and behavior,little is known about the mechanisms that may underlie those effects,and even less about treatments that might reverse them.Recent studies from our laboratory have indicated that AIE produced enduring changes in astrocyte function and synaptic activity in the hippocampal formation,suggesting the possibility of an alteration in astrocyte-neuronal connectivity and function.We utilized astrocyte-specific,membrane restricted viral labeling paired with immunohistochemistry to perform confocal single cell astrocyte imaging,three-dimensional reconstruction,and quantification of astrocyte morphology in hippocampal area CA1 from adult rats after AIE.Additionally,we assessed the colocalization of astrocyte plasma membrane labeling with immunoreactivity for AMPA-(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)glutamate receptor 1,an AMPA receptor subunit and established neuronal marker of excitatory synapses,as a metric of astrocyte-synapse proximity.AIE significantly reduced the colocalization of the astrocyte plasma membrane with synaptic marker puncta in adulthood.This is striking in that it suggests not only an alteration of the physical association of astrocytes with synapses by AIE,but one that lasts into adulthood-well after the termination of alcohol exposure.Perhaps even more notable,the AIE-induced reduction of astrocyte-synapse interaction was reversed by sub-chronic treatment with the clinically used agent,gabapentin(Neurontin),in adulthood.This suggests that a medication in common clinical use may have the potential to reverse some of the enduring effects of adolescent alcohol exposure on brain function.All animal experiments conducted were approved by the Duke University Institutional Animal Care and Use Committee(Protocol Registry Number A159-18-07)on July 27,2018.展开更多
Objective: This prospective randomized study aimed to evaluate the effect of IV lidocaine infusion or gabapentin and their combination in providing efficient analgesia after thyroid surgery. Methods: Eighty-eight pati...Objective: This prospective randomized study aimed to evaluate the effect of IV lidocaine infusion or gabapentin and their combination in providing efficient analgesia after thyroid surgery. Methods: Eighty-eight patients scheduled for thyroidectomy were randomized into four equal groups (n = 22). Group P (placebo) patients received placebo capsules 1 h preoperatively and intravenous (IV) saline infusion. Group L (Lidocaine): patients received placebo capsules 1 h preoperatively and IV bolus lidocaine 1.0 mg/kg followed by infusion 2 mg/kg/h. Group G (Gabapentin) patients received 600 mg gabapentin capsules 1 h preoperatively and IV saline infusion. Group LG (Lidocaine-Gabapentin) patients received 600 mg gabapentin capsules 1 h preoperatively and IV bolus of 1.0 mg/kg lidocaine followed by infusion 2 mg/kg/h. (lidocaine or saline infusion started before induction of anesthesia and continued until the end of surgery). Intraoperative fentanyl consumption and hemodynamic changes were recorded. Postoperative total tramadol consumption, time to first analgesic request, visual analog scale (VAS) of pain, sedation level, and side effects were assessed for 24 hours. Results: (LG) group had significant lower intraoperative fentanyl and lower postoperative tramadol consumption (p < 0.001) compared to (P), (L) and (G) groups, with prolonged time of first analgesic request (p < 0.001) compared to (P) and (L) groups, and lower VAS compared to other groups (p < 0.001 or p < 0.01). There was significantly lower postoperative nausea and vomiting (PONV) in G & LG groups compared to (P) group (p < 0.01). Conclusion: The combination of preoperative gabapentin and intraoperative lidocaine infusion provided more analgesic effect than either drug alone with lower and more delayed postoperative analgesic requirements and lower VAS. (PONV) was lower in groups received gabapentin.展开更多
Objective: To examine the efficacy of gabapentin for the treatment of behavioral and psychological symptoms of dementia (BPSD). Design: A retrospective chart review. Settings: Tertiary care geriatric psychiatry inpati...Objective: To examine the efficacy of gabapentin for the treatment of behavioral and psychological symptoms of dementia (BPSD). Design: A retrospective chart review. Settings: Tertiary care geriatric psychiatry inpatient unit. Participants: 230 patients with BPSD. Measurements: The socio-demographic information, type of behaviors, co-morbid psychiatric and medical diagnoses, daily doses of medications and side-effects were recorded. Results: Of the 230 patients, 22 were treated with gabapentin. Twenty of these patients were on a combination of gabapentin and an antipsychotic medication while two patients were treated with gabapentin monotherapy. Eighteen of the 20 patients in the combination group tolerated the treatments with little or no side effects as did the two patients in the monotherapy group. Conclusions: Gabapentin may be a safe option for the treatment of BPSD in combination with antipsychotic medications. Gabapentin may also be effective as monotherapy in certain patients with BPSD.展开更多
A highly simple, rapid, sensitive and selective method is developed for spectrophotometric determination of gabapentin in pure form as well as in pharmaceutical formulations. The method is based on the formation of a ...A highly simple, rapid, sensitive and selective method is developed for spectrophotometric determination of gabapentin in pure form as well as in pharmaceutical formulations. The method is based on the formation of a yellow Schiff base derived from the condensation of gabapentin drug (1-amino methyl) cyclo hexane acetic acid and 2,5-dihydroxybenzaldehyde (DHBA) exhibiting a maximum absorbance at 445 nm. The composition, molar absorptivity and effect of different excipient have been determined spectrophotometrically. Under optimized experimental conditions, Beer’s law is obeyed in the concentration range 2.57 - 37.25 μg/ml. The method is validated with respect to accuracy, precision, limit of detection and limit of quantification. The Sandell sensitivity, correlation coefficient and regression equation are calculated. The equilibrium constant and free energy change using Benesi-Hildebrand plot are also determined. The Schiff base derived from condensation of gabapentin with DHBA is also synthesized and characterized. The condensation reaction mechanism has been proposed.展开更多
<b>Background & Aims:</b> The multimodal analgesia provides superior pain relief and reduces opioid consumption and its side effects. Gabapentin has been used successfully in multi-modal analgesia in d...<b>Background & Aims:</b> The multimodal analgesia provides superior pain relief and reduces opioid consumption and its side effects. Gabapentin has been used successfully in multi-modal analgesia in different doses. We designed a double-blind randomized control trial to find the minimal effective dose of gabapentin in multimodal analgesia for postoperative pain following total abdominal hysterectomy. <b>Material & Methods:</b> After informed consent, total of 87 patients were randomly assigned to A, B & C groups to receive gabapentin orally 300 mg, 600 mg, and 900 mg respectively one to two hours before surgery. Postoperatively pain was managed by patient-controlled analgesia (PCA) using pethidine. Pain score, opioid consumption, and side effects of gabapentin were monitored. Rescue analgesia was given and monitored. <b>Results:</b> There was no statistically significant difference among the groups with respect to age, weight, height, pethidine consumption, and rescue analgesia. Mean pain scores were statistically insignificant at baseline, 8, 12, and 24 hours postoperatively. Only at 4 hours, the highest pain score (mean) was found in group A, which is statistically significant. The side effects of gabapentin like nausea, vomiting, somnolence, and dizziness were also statistically insignificant. <b>Conclusion:</b> A single preoperative oral gabapentin 300 mg was found to be minimal effective dose in multimodal analgesic regimen for reducing post-operative pain and analgesic requirement following total abdominal hysterectomy.展开更多
Gabapentin undergoes intramolecular cyclization by alkylamine nucleophilic attacking on carboxylate carbonyl. And the above self-dehydration condensation can produce gabapentin lactam which has some toxic effects. The...Gabapentin undergoes intramolecular cyclization by alkylamine nucleophilic attacking on carboxylate carbonyl. And the above self-dehydration condensation can produce gabapentin lactam which has some toxic effects. Therefore, in order to decrease the above subsidiary reaction, the effects of several metal ions on the reaction mechanism and the potential barriers of self-dehydration condensation of gabapentin are analyzed. Each molecular structure of gabapentin in the presence of several metal ions is optimized using the density functional theory(DFT) with B3LYP method at the 6-311+G(d,p) basis set level. And its geometric and thermodynamic parameters are also investigated. The calculated results showed that gabapentin can form stable complexes with divalent metal ions and exhibit the highest affinity for small and highly charged metal cations. The binding ability of these metal ions with gabapentin ranks in an order of Fe^2+>Zn^2+> Mg^2+> Ca^2+> Na^+> K^+. Besides, the potential barriers of subsidiary reaction of gabapentin increase obviously in the presence of several metal ions than that of free gabapentin. This means that the above metal ions can inhibit effectively the intramolecular cyclization of gabapentin.展开更多
Objective:To assess the efficacy of gabapentin in the treatment of low back pain patients.Methods:This prospective observational study was conducted over 6 months to assess the efficacy of gabapentin in patients suffe...Objective:To assess the efficacy of gabapentin in the treatment of low back pain patients.Methods:This prospective observational study was conducted over 6 months to assess the efficacy of gabapentin in patients suffering from low back pain.Past medical history,pain severity by Visual Analogue scale(VAS)and sleep quality by Pittsburgh Sleep Quality Index(PQSI)were collected.VAS scores and PQSI scores before and after gabapentin treatment were compared,and gabapentin satisfaction post treatment were recorded.Results:This study included 100 low back pain patients with 65 males and 35 females,and the mean age was(39.0±10.5)years.The commonest presentation was non-radiating low back pain(40%).The mean VAS score and the mean PQSI score in the study before treatment were 7.70±1.91 and 10.95±5.02,respectively.After treatment with gabapentin,the mean VAS score and the mean PQSI score decreased to 2.75±1.79 and 4.90±2.20,respectively,and the differences before and after the treatment were significantly different(both P=0.001).Overall,62%of the patients were extremely satisfied with gabapentin because they reported no adverse drug reaction.Besides,31%of the patients were satisfied and 7%were strongly dissatisfied with the therapy.Conclusion:Gabapentin can improve sleep quality and reduce lower back pain as measured by the VAS and PQSI.The efficacy of this drug is relatively good,but further improvement is required.展开更多
The objective of the present study was to examine the influence of cosolvent system and micro-emulsion formulation on in-vitro skin permeation of gabapentin, furthermore, to characterize the physicochemical properties...The objective of the present study was to examine the influence of cosolvent system and micro-emulsion formulation on in-vitro skin permeation of gabapentin, furthermore, to characterize the physicochemical properties of drug-loaded oil-in-water (o/w) and water-in-oil (w/o) cremophor 40-based microemulsions in comparison to the blank counterparts. The cosolvent system prepared by homogenous mixing is composed of ethanol-water and propylene glycol-water mixture (90:10, 80:20, 70:30 v/v) respectively. The microemulsion consisted of coconut oil, water and mixture of cremophor 40 (surfactant) and ethanol (cosurfactant) and was prepared by aqueous phase titration method. Physicochemical properties of microemulsions were determined using reported procedures. Transdermal flux for gabapentin was studied in-vitro using modified Franz diffusion cells. The physicochemical properties of drug-loaded microemulsions and their blank counterparts were generally alike, however, slight variation in pH and viscosity was observed probably due to the intrinsic properties of the drug. The ethanol-water system (70:30 v/v) gave higher flux for gabapentin when compared to propylene glycol-water system (70:30 v/v). The w/o microemulsion formulations resulted in, higher flux for gabapentin when compared to o/w formulations. FTIR spectra of the untreated stratum corneum, when compared to cosolvent system and microemulsion treated stratum corneum, suggest the mechanism of permeation to be disruption of lipid bilayers and keratin denaturation of the stratum corneum. The results show that incorporation of gabapentin into microemulsions did not change the microemulsion type. The in vitro permeation data obtained from experimental work suggest that the cosolvent system (ethanol-water 70:30 v/v) and w/o microemulsion formulations respectively, can be successfully used as potential vehicles in developing transdermal therapeutic systems for gabapentin.展开更多
Gabapentin, and pregabalin had been used in analgesic field some studies. This double blind randomized clinical trial was conducted to evaluate the pre-emptive use of gabapentin 900 mg and pregabalin 300 mg in reducin...Gabapentin, and pregabalin had been used in analgesic field some studies. This double blind randomized clinical trial was conducted to evaluate the pre-emptive use of gabapentin 900 mg and pregabalin 300 mg in reducing postoperative pain. Methods: A total number of 75 patients undergoing lower gynecological procedures were prospectively randomized, into three groups (group A, B and C), each group including 25 patients with total 75 patients. Pregabalin, gabapentin or placebo, the pain was assessed on a visual analogue scale (VAS) at 0, 6, 12, 18 & 24 hours postoperatively. Duration of effective analgesia was documented, and administration of extra analgesic doses of meperedine required in the first 24 hours. Results: Patients in the gabapentin or pregabalin had significantly lower VAS scores at 6, 12, 18 and 24 hours, than those in the placebo group. As for rescue analgesia with mepredine consumed in the gabapentin, and pregabalin were significantly less than in the placebo. As for the complications, both drugs had increased incidence of nausea, vomiting and dizziness postoperatively, while no significance was found between all groups as regard hypotension, bradycardia and shivering. Conclusion: Preoperative use of pregabalin or gabapentin provides comparable but significant prolonged postoperative analgesia, less nausea and vomiting compared to placebo after gynecological surgeries. However, it was associated with increased incidence of postoperative dizziness.展开更多
Pain is defined as an unpleasant sensory and emotional experience, associated with actual or potential tissue damage. According to its neurobiological mechanism, pain is classified into nociceptive, inflammatory, dysf...Pain is defined as an unpleasant sensory and emotional experience, associated with actual or potential tissue damage. According to its neurobiological mechanism, pain is classified into nociceptive, inflammatory, dysfunctional, and neuropathic. Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory nervous system. Both pregabalin and gabapentin are pharmaceuticals used as validation drugs in experimental models of NP. Pregabalin was shown to produce significant antihyperalgesic and antiallodynic effects. Gabapentin is used as a reference compound for new analgesics and reduces tactile allodynia in rats. The aim of this work is to evaluate pregabalin and gabapentin effects on nociceptive behaviors induced by spinal nerve ligation (SNL). Female Wistar rats of 140 - 160 g were used, divided into five groups: Naive, SHAM, SNL rats treated with saline solution, SNL rats treated with pregabalin 30 mg/kg p.o., SNL rats treated with gabapentin 300 mg/kg p.o. Nociceptive behaviors were determined by the up and down method. In the establishment of SNL-induced allodynic behavior, a reduction in paw withdrawal threshold was observed in the time course, which was present from day 1 and it was maintained for 28 days post-ligation. With the administration of pregabalin and gabapentin, anti-allodynic behavior was observed in the time course and in the areas under the curve (AUC) of the time course of anti-allodynic behavior, significant difference was observed between pregabalin, and gabapentin groups compared to vehicle with a value of p < 0.0001. The results showed pregabalin and gabapentin induce an antinociceptive effect in rats subjected to SNL.展开更多
<strong>Background:</strong><span style="font-family:;" "=""><span style="font-family:Verdana;"> Gabapentin is routinely prescribed preoperatively to decrease...<strong>Background:</strong><span style="font-family:;" "=""><span style="font-family:Verdana;"> Gabapentin is routinely prescribed preoperatively to decrease postoperative pain intensity. It is included in the enhanced recovery after surgery (ERAS) recommendations. </span><b><span style="font-family:Verdana;">Objective:</span></b><span style="font-family:Verdana;"> To analyze correlation of gabapentin dosage and post anesthesia care unit (PACU) length of stay (LOS) and cost. </span><b><span style="font-family:Verdana;">Study Design:</span></b><span style="font-family:Verdana;"> A retrospective chart review of patients who underwent general anesthesia and received preoperative oral gabapentin from June 2017 </span></span><span style="font-family:Verdana;">to</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> August 2017 for pelvic and breast procedures. The main outcome was correlation between PACU LOS and gabapentin dosage in the outpatients. Financial analysis was performed to assess the cost to the hospital associated with increased LOS. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> Of the 636 patients, 405 patients received 300 </span><span style="font-family:Verdana;">mg and 231 patients received 100 mg gabapentin. Mean dosage per kg (mg/k</span><span style="font-family:Verdana;">g ±</span></span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">SD) was 3.12</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">±</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">1.51 (range: </span><span style="font-family:Verdana;">0</span><span style="font-family:Verdana;">.86 to 6.12). PACU LOS was 96</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">±</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">77 (minutes ±</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">SD) in patients receiving 100 mg and 120</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">±</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">96 in patients receiving 300 mg capsule (p</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">=</span><span style="font-family:;" "=""> </span><span style="font-family:;" "=""><span style="font-family:Verdana;">0.001). Linear regression analysis, failed to show a </span><span style="font-family:Verdana;">statistically significant correlation between per kg dosage and PACU LOS (</span><span style="font-family:Verdana;">p</span></span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">=</span><span style="font-family:Verdana;"> 0</span><span style="font-family:Verdana;">.13). Using multiple regression analysis, we calculated the correlation coefficient to be +1.71 minutes per 1mg/kg gabapentin (95% CI: -</span><span style="font-family:Verdana;">3.75 to +7.10, p</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">=</span><span style="font-family:Verdana;"> 0</span><span style="font-family:Verdana;">.54) after adjusting for confounders. Adding 3</span><span style="font-family:;" "=""> </span><span style="font-family:;" "=""><span style="font-family:Verdana;">mg/kg to pre-op g</span><span style="font-family:Verdana;">abapentin dosage of all outpatients cost on average</span></span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> an extra $9794 per mo</span><span style="font-family:;" "=""><span style="font-family:Verdana;">nth in this cohort. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Every 1mg/kg increase in gabapentin dosage adds an estimated 7.1 minutes to PACU LOS. A 3</span></span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">mg/kg increase in gabapentin adds estimated 22 additional minutes in PACU LOS. Unfortunately, increase LOS is associated with increased hospital costs.</span>展开更多
The aim of this study was to investigate the role of endogenous enkephalin in the cerebral antihyperalgesic action of gabapentin.Neuropathic pain models and antihyperalgesic effect of gabapentin were confirmed by the ...The aim of this study was to investigate the role of endogenous enkephalin in the cerebral antihyperalgesic action of gabapentin.Neuropathic pain models and antihyperalgesic effect of gabapentin were confirmed by the presentation and changes of mechanical allodynia and thermal hyperalgesia of operated mouse hind paws.The results suggested that endogenous enkephalin may not be involved in the antihyperalgesic effect of gabapentin.展开更多
Background Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether...Background Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca^2＋/calmodulin-dependent protein kinase Ⅱ （CaMKⅡ） contributes to the analgesic effect of gabapentin on a chronic constriction injury （CCI） model. Methods Gabapentin （2%, 100 mg/kg） or saline （0.5 ml/100 g） was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0-4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKⅡ were quantified by reverse-transcriptional polymerase chain reaction and Western blotting. Results The analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKⅡ and phosphorylated CaMKⅡ in CCI rats. Conclusion The analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKⅡ in the spinal cord.展开更多
文摘Objective： To evaluate the analgesic efficacy of controlled-release （CR） oxycodone and gabapentin in malignant neuropathic pain （NP）. Methods： Patients with malignant NP were enrolled and baseline pain intensity （PI） was recorded. They initially took one week CR oxycodone and were allocated to two different groups at day 8 by reevaluated PI. Patients with mild pain went to CR oxycodone mono-therapy group （OO group） and took another two weeks CR oxycodone. Others went to （CR oxycodone combined gabapentin group （OG group） and received additional gabapentin. Daily doses and side effects were recorded. Results： Fifty-eight （92.06%） of the 63 enrolled patients completed the initial week＇s therapy. Twenty-two （37.93%） went to OO group and PI significantly reduced at day 15 （2.00 vs. 2.62, P=0.004）, but not improved at day 22 （1.90 vs. 2.00, P=0.54）. Thirty-six （62.07%） patients went to OG group and PI was significantly reduced at day 15 （4,47 vs. 2.94, P〈0.001）, but not improved at day 22 （2.94 vs. 2.75, P=0.136）. Mean daily dose （MDD） of CR oxycodone at day 8 was 62.64 mg. It was significantly increased at days 15 and 22 （71.43 mg vs. 62.64 rag, P=0.021; 81.90 mg vs. 71.43 mg, P=0.004） in OO group. MDD of gabapentin was significantly increased at day 22 compared to day 15 （862.50 mg vs. 993.75 mg, P〈0.001）. Constipation was occurred in 13.64% of the patients in OO group and 14.26 % in OG group. Conclusion： Malignant NP may be well controlled by oxycodone mono-therapy. Early combination with gabapentin is sensible when pain is not satisfactory relieved by oxycodone alone. The side effects of them are manageable.
基金supported by the National Institute on Alcohol Abuse and Alcoholism(NIAAA)Neurobiology of Adolescent Drinking In Adulthood(NADIA)Grant#2U01AA019925(to HSS)the National Institute on Alcohol Abuse and Alcoholism(NIAAA)R00AA022651(to TAW)the National Institute on Drug Abuse(NIDA)R01DA041455(to KJR)
文摘Adolescent alcohol abuse is a substantive public health problem that has been the subject of intensive study in recent years.Despite reports of a wide range of effects of adolescent intermittent ethanol(AIE)exposure on brain and behavior,little is known about the mechanisms that may underlie those effects,and even less about treatments that might reverse them.Recent studies from our laboratory have indicated that AIE produced enduring changes in astrocyte function and synaptic activity in the hippocampal formation,suggesting the possibility of an alteration in astrocyte-neuronal connectivity and function.We utilized astrocyte-specific,membrane restricted viral labeling paired with immunohistochemistry to perform confocal single cell astrocyte imaging,three-dimensional reconstruction,and quantification of astrocyte morphology in hippocampal area CA1 from adult rats after AIE.Additionally,we assessed the colocalization of astrocyte plasma membrane labeling with immunoreactivity for AMPA-(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)glutamate receptor 1,an AMPA receptor subunit and established neuronal marker of excitatory synapses,as a metric of astrocyte-synapse proximity.AIE significantly reduced the colocalization of the astrocyte plasma membrane with synaptic marker puncta in adulthood.This is striking in that it suggests not only an alteration of the physical association of astrocytes with synapses by AIE,but one that lasts into adulthood-well after the termination of alcohol exposure.Perhaps even more notable,the AIE-induced reduction of astrocyte-synapse interaction was reversed by sub-chronic treatment with the clinically used agent,gabapentin(Neurontin),in adulthood.This suggests that a medication in common clinical use may have the potential to reverse some of the enduring effects of adolescent alcohol exposure on brain function.All animal experiments conducted were approved by the Duke University Institutional Animal Care and Use Committee(Protocol Registry Number A159-18-07)on July 27,2018.
文摘Objective: This prospective randomized study aimed to evaluate the effect of IV lidocaine infusion or gabapentin and their combination in providing efficient analgesia after thyroid surgery. Methods: Eighty-eight patients scheduled for thyroidectomy were randomized into four equal groups (n = 22). Group P (placebo) patients received placebo capsules 1 h preoperatively and intravenous (IV) saline infusion. Group L (Lidocaine): patients received placebo capsules 1 h preoperatively and IV bolus lidocaine 1.0 mg/kg followed by infusion 2 mg/kg/h. Group G (Gabapentin) patients received 600 mg gabapentin capsules 1 h preoperatively and IV saline infusion. Group LG (Lidocaine-Gabapentin) patients received 600 mg gabapentin capsules 1 h preoperatively and IV bolus of 1.0 mg/kg lidocaine followed by infusion 2 mg/kg/h. (lidocaine or saline infusion started before induction of anesthesia and continued until the end of surgery). Intraoperative fentanyl consumption and hemodynamic changes were recorded. Postoperative total tramadol consumption, time to first analgesic request, visual analog scale (VAS) of pain, sedation level, and side effects were assessed for 24 hours. Results: (LG) group had significant lower intraoperative fentanyl and lower postoperative tramadol consumption (p < 0.001) compared to (P), (L) and (G) groups, with prolonged time of first analgesic request (p < 0.001) compared to (P) and (L) groups, and lower VAS compared to other groups (p < 0.001 or p < 0.01). There was significantly lower postoperative nausea and vomiting (PONV) in G & LG groups compared to (P) group (p < 0.01). Conclusion: The combination of preoperative gabapentin and intraoperative lidocaine infusion provided more analgesic effect than either drug alone with lower and more delayed postoperative analgesic requirements and lower VAS. (PONV) was lower in groups received gabapentin.
文摘Objective: To examine the efficacy of gabapentin for the treatment of behavioral and psychological symptoms of dementia (BPSD). Design: A retrospective chart review. Settings: Tertiary care geriatric psychiatry inpatient unit. Participants: 230 patients with BPSD. Measurements: The socio-demographic information, type of behaviors, co-morbid psychiatric and medical diagnoses, daily doses of medications and side-effects were recorded. Results: Of the 230 patients, 22 were treated with gabapentin. Twenty of these patients were on a combination of gabapentin and an antipsychotic medication while two patients were treated with gabapentin monotherapy. Eighteen of the 20 patients in the combination group tolerated the treatments with little or no side effects as did the two patients in the monotherapy group. Conclusions: Gabapentin may be a safe option for the treatment of BPSD in combination with antipsychotic medications. Gabapentin may also be effective as monotherapy in certain patients with BPSD.
文摘A highly simple, rapid, sensitive and selective method is developed for spectrophotometric determination of gabapentin in pure form as well as in pharmaceutical formulations. The method is based on the formation of a yellow Schiff base derived from the condensation of gabapentin drug (1-amino methyl) cyclo hexane acetic acid and 2,5-dihydroxybenzaldehyde (DHBA) exhibiting a maximum absorbance at 445 nm. The composition, molar absorptivity and effect of different excipient have been determined spectrophotometrically. Under optimized experimental conditions, Beer’s law is obeyed in the concentration range 2.57 - 37.25 μg/ml. The method is validated with respect to accuracy, precision, limit of detection and limit of quantification. The Sandell sensitivity, correlation coefficient and regression equation are calculated. The equilibrium constant and free energy change using Benesi-Hildebrand plot are also determined. The Schiff base derived from condensation of gabapentin with DHBA is also synthesized and characterized. The condensation reaction mechanism has been proposed.
文摘<b>Background & Aims:</b> The multimodal analgesia provides superior pain relief and reduces opioid consumption and its side effects. Gabapentin has been used successfully in multi-modal analgesia in different doses. We designed a double-blind randomized control trial to find the minimal effective dose of gabapentin in multimodal analgesia for postoperative pain following total abdominal hysterectomy. <b>Material & Methods:</b> After informed consent, total of 87 patients were randomly assigned to A, B & C groups to receive gabapentin orally 300 mg, 600 mg, and 900 mg respectively one to two hours before surgery. Postoperatively pain was managed by patient-controlled analgesia (PCA) using pethidine. Pain score, opioid consumption, and side effects of gabapentin were monitored. Rescue analgesia was given and monitored. <b>Results:</b> There was no statistically significant difference among the groups with respect to age, weight, height, pethidine consumption, and rescue analgesia. Mean pain scores were statistically insignificant at baseline, 8, 12, and 24 hours postoperatively. Only at 4 hours, the highest pain score (mean) was found in group A, which is statistically significant. The side effects of gabapentin like nausea, vomiting, somnolence, and dizziness were also statistically insignificant. <b>Conclusion:</b> A single preoperative oral gabapentin 300 mg was found to be minimal effective dose in multimodal analgesic regimen for reducing post-operative pain and analgesic requirement following total abdominal hysterectomy.
基金supported by the National Natural Science Fundation of China(No.51776130)the Natural Science Foundation of Shanghai(No.12ZR1420400)Innovation Foundation from the Education Commission of Shanghai City(No.14YZ092)
文摘Gabapentin undergoes intramolecular cyclization by alkylamine nucleophilic attacking on carboxylate carbonyl. And the above self-dehydration condensation can produce gabapentin lactam which has some toxic effects. Therefore, in order to decrease the above subsidiary reaction, the effects of several metal ions on the reaction mechanism and the potential barriers of self-dehydration condensation of gabapentin are analyzed. Each molecular structure of gabapentin in the presence of several metal ions is optimized using the density functional theory(DFT) with B3LYP method at the 6-311+G(d,p) basis set level. And its geometric and thermodynamic parameters are also investigated. The calculated results showed that gabapentin can form stable complexes with divalent metal ions and exhibit the highest affinity for small and highly charged metal cations. The binding ability of these metal ions with gabapentin ranks in an order of Fe^2+>Zn^2+> Mg^2+> Ca^2+> Na^+> K^+. Besides, the potential barriers of subsidiary reaction of gabapentin increase obviously in the presence of several metal ions than that of free gabapentin. This means that the above metal ions can inhibit effectively the intramolecular cyclization of gabapentin.
文摘Objective:To assess the efficacy of gabapentin in the treatment of low back pain patients.Methods:This prospective observational study was conducted over 6 months to assess the efficacy of gabapentin in patients suffering from low back pain.Past medical history,pain severity by Visual Analogue scale(VAS)and sleep quality by Pittsburgh Sleep Quality Index(PQSI)were collected.VAS scores and PQSI scores before and after gabapentin treatment were compared,and gabapentin satisfaction post treatment were recorded.Results:This study included 100 low back pain patients with 65 males and 35 females,and the mean age was(39.0±10.5)years.The commonest presentation was non-radiating low back pain(40%).The mean VAS score and the mean PQSI score in the study before treatment were 7.70±1.91 and 10.95±5.02,respectively.After treatment with gabapentin,the mean VAS score and the mean PQSI score decreased to 2.75±1.79 and 4.90±2.20,respectively,and the differences before and after the treatment were significantly different(both P=0.001).Overall,62%of the patients were extremely satisfied with gabapentin because they reported no adverse drug reaction.Besides,31%of the patients were satisfied and 7%were strongly dissatisfied with the therapy.Conclusion:Gabapentin can improve sleep quality and reduce lower back pain as measured by the VAS and PQSI.The efficacy of this drug is relatively good,but further improvement is required.
文摘The objective of the present study was to examine the influence of cosolvent system and micro-emulsion formulation on in-vitro skin permeation of gabapentin, furthermore, to characterize the physicochemical properties of drug-loaded oil-in-water (o/w) and water-in-oil (w/o) cremophor 40-based microemulsions in comparison to the blank counterparts. The cosolvent system prepared by homogenous mixing is composed of ethanol-water and propylene glycol-water mixture (90:10, 80:20, 70:30 v/v) respectively. The microemulsion consisted of coconut oil, water and mixture of cremophor 40 (surfactant) and ethanol (cosurfactant) and was prepared by aqueous phase titration method. Physicochemical properties of microemulsions were determined using reported procedures. Transdermal flux for gabapentin was studied in-vitro using modified Franz diffusion cells. The physicochemical properties of drug-loaded microemulsions and their blank counterparts were generally alike, however, slight variation in pH and viscosity was observed probably due to the intrinsic properties of the drug. The ethanol-water system (70:30 v/v) gave higher flux for gabapentin when compared to propylene glycol-water system (70:30 v/v). The w/o microemulsion formulations resulted in, higher flux for gabapentin when compared to o/w formulations. FTIR spectra of the untreated stratum corneum, when compared to cosolvent system and microemulsion treated stratum corneum, suggest the mechanism of permeation to be disruption of lipid bilayers and keratin denaturation of the stratum corneum. The results show that incorporation of gabapentin into microemulsions did not change the microemulsion type. The in vitro permeation data obtained from experimental work suggest that the cosolvent system (ethanol-water 70:30 v/v) and w/o microemulsion formulations respectively, can be successfully used as potential vehicles in developing transdermal therapeutic systems for gabapentin.
文摘Gabapentin, and pregabalin had been used in analgesic field some studies. This double blind randomized clinical trial was conducted to evaluate the pre-emptive use of gabapentin 900 mg and pregabalin 300 mg in reducing postoperative pain. Methods: A total number of 75 patients undergoing lower gynecological procedures were prospectively randomized, into three groups (group A, B and C), each group including 25 patients with total 75 patients. Pregabalin, gabapentin or placebo, the pain was assessed on a visual analogue scale (VAS) at 0, 6, 12, 18 & 24 hours postoperatively. Duration of effective analgesia was documented, and administration of extra analgesic doses of meperedine required in the first 24 hours. Results: Patients in the gabapentin or pregabalin had significantly lower VAS scores at 6, 12, 18 and 24 hours, than those in the placebo group. As for rescue analgesia with mepredine consumed in the gabapentin, and pregabalin were significantly less than in the placebo. As for the complications, both drugs had increased incidence of nausea, vomiting and dizziness postoperatively, while no significance was found between all groups as regard hypotension, bradycardia and shivering. Conclusion: Preoperative use of pregabalin or gabapentin provides comparable but significant prolonged postoperative analgesia, less nausea and vomiting compared to placebo after gynecological surgeries. However, it was associated with increased incidence of postoperative dizziness.
文摘Pain is defined as an unpleasant sensory and emotional experience, associated with actual or potential tissue damage. According to its neurobiological mechanism, pain is classified into nociceptive, inflammatory, dysfunctional, and neuropathic. Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory nervous system. Both pregabalin and gabapentin are pharmaceuticals used as validation drugs in experimental models of NP. Pregabalin was shown to produce significant antihyperalgesic and antiallodynic effects. Gabapentin is used as a reference compound for new analgesics and reduces tactile allodynia in rats. The aim of this work is to evaluate pregabalin and gabapentin effects on nociceptive behaviors induced by spinal nerve ligation (SNL). Female Wistar rats of 140 - 160 g were used, divided into five groups: Naive, SHAM, SNL rats treated with saline solution, SNL rats treated with pregabalin 30 mg/kg p.o., SNL rats treated with gabapentin 300 mg/kg p.o. Nociceptive behaviors were determined by the up and down method. In the establishment of SNL-induced allodynic behavior, a reduction in paw withdrawal threshold was observed in the time course, which was present from day 1 and it was maintained for 28 days post-ligation. With the administration of pregabalin and gabapentin, anti-allodynic behavior was observed in the time course and in the areas under the curve (AUC) of the time course of anti-allodynic behavior, significant difference was observed between pregabalin, and gabapentin groups compared to vehicle with a value of p < 0.0001. The results showed pregabalin and gabapentin induce an antinociceptive effect in rats subjected to SNL.
文摘<strong>Background:</strong><span style="font-family:;" "=""><span style="font-family:Verdana;"> Gabapentin is routinely prescribed preoperatively to decrease postoperative pain intensity. It is included in the enhanced recovery after surgery (ERAS) recommendations. </span><b><span style="font-family:Verdana;">Objective:</span></b><span style="font-family:Verdana;"> To analyze correlation of gabapentin dosage and post anesthesia care unit (PACU) length of stay (LOS) and cost. </span><b><span style="font-family:Verdana;">Study Design:</span></b><span style="font-family:Verdana;"> A retrospective chart review of patients who underwent general anesthesia and received preoperative oral gabapentin from June 2017 </span></span><span style="font-family:Verdana;">to</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> August 2017 for pelvic and breast procedures. The main outcome was correlation between PACU LOS and gabapentin dosage in the outpatients. Financial analysis was performed to assess the cost to the hospital associated with increased LOS. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> Of the 636 patients, 405 patients received 300 </span><span style="font-family:Verdana;">mg and 231 patients received 100 mg gabapentin. Mean dosage per kg (mg/k</span><span style="font-family:Verdana;">g ±</span></span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">SD) was 3.12</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">±</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">1.51 (range: </span><span style="font-family:Verdana;">0</span><span style="font-family:Verdana;">.86 to 6.12). PACU LOS was 96</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">±</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">77 (minutes ±</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">SD) in patients receiving 100 mg and 120</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">±</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">96 in patients receiving 300 mg capsule (p</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">=</span><span style="font-family:;" "=""> </span><span style="font-family:;" "=""><span style="font-family:Verdana;">0.001). Linear regression analysis, failed to show a </span><span style="font-family:Verdana;">statistically significant correlation between per kg dosage and PACU LOS (</span><span style="font-family:Verdana;">p</span></span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">=</span><span style="font-family:Verdana;"> 0</span><span style="font-family:Verdana;">.13). Using multiple regression analysis, we calculated the correlation coefficient to be +1.71 minutes per 1mg/kg gabapentin (95% CI: -</span><span style="font-family:Verdana;">3.75 to +7.10, p</span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">=</span><span style="font-family:Verdana;"> 0</span><span style="font-family:Verdana;">.54) after adjusting for confounders. Adding 3</span><span style="font-family:;" "=""> </span><span style="font-family:;" "=""><span style="font-family:Verdana;">mg/kg to pre-op g</span><span style="font-family:Verdana;">abapentin dosage of all outpatients cost on average</span></span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> an extra $9794 per mo</span><span style="font-family:;" "=""><span style="font-family:Verdana;">nth in this cohort. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Every 1mg/kg increase in gabapentin dosage adds an estimated 7.1 minutes to PACU LOS. A 3</span></span><span style="font-family:;" "=""> </span><span style="font-family:Verdana;">mg/kg increase in gabapentin adds estimated 22 additional minutes in PACU LOS. Unfortunately, increase LOS is associated with increased hospital costs.</span>
文摘The aim of this study was to investigate the role of endogenous enkephalin in the cerebral antihyperalgesic action of gabapentin.Neuropathic pain models and antihyperalgesic effect of gabapentin were confirmed by the presentation and changes of mechanical allodynia and thermal hyperalgesia of operated mouse hind paws.The results suggested that endogenous enkephalin may not be involved in the antihyperalgesic effect of gabapentin.
基金This research is supported by a grant from the National Natural Science Foundation of China （No. 30672029）.
文摘Background Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca^2＋/calmodulin-dependent protein kinase Ⅱ （CaMKⅡ） contributes to the analgesic effect of gabapentin on a chronic constriction injury （CCI） model. Methods Gabapentin （2%, 100 mg/kg） or saline （0.5 ml/100 g） was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0-4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKⅡ were quantified by reverse-transcriptional polymerase chain reaction and Western blotting. Results The analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKⅡ and phosphorylated CaMKⅡ in CCI rats. Conclusion The analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKⅡ in the spinal cord.
