Field MJ, Holloman EF, McCleary S, Hughes J, Singh L: Evaluation of gabapentin and S-(+)-isobutylgaba in a rat model of postoperative pain. J Pharmacol Exp Ther 282: 1242-6
Gabapentin and S-(+)-3-isobutylgaba are anticonvulsant agents that selectively interact with the alpha2delta subunit of voltage-dependent calcium channels. This report describes the activities of these two compounds in a rat model of postoperative pain. An incision of the plantaris muscle of a hind paw induced thermal hyperalgesia and tactile allodynia lasting at least 3 days. Postoperative testing was carried out using the plantar test for thermal hyperalgesia and von Frey hairs for tactile allodynia. A single s.c. dose of gabapentin, 1 h before surgery, dose-dependently (3-30 mg/kg) blocked the development of allodynia and hyperalgesia with a minimum effective dose (MED) of 10 and 30 mg/kg, respectively. The highest dose of gabapentin prevented development of hyperalgesia and allodynia for 24 and 49 h, respectively. Similar administration of S-(+)-3-isobutylgaba also dose-dependently (3-30 mg/kg, s.c.) prevented development of hyperalgesia and allodynia with MED of 3 and 10 mg/kg, respectively. The highest dose of S-(+)-3-isobutylgaba completely blocked development of both nociceptive responses for 3 days. The administration of S-(+)-3-isobutylgaba (30 mg/kg s.c.) 1 h after surgery also completely blocked the maintenance of hyperalgesia and allodynia, but its duration of action was much shorter (3 h). The administration of morphine (1-6 mg/kg s.c.) 0.5 h before surgery prevented the development of thermal hyperalgesia with a MED of 1 mg/kg. However, unlike gabapentin and S-(+)-3-isobutylgaba, it had little effect on the development of tactile allodynia. It is suggested that gabapentin and S-(+)-3-isobutylgaba may be effective in the treatment of postoperative pain.
Available from: Dong Tang
- "Within neurons of the DRG the activity of calcium channels has been shown to play an important role in nociceptive processing [2,3] and regulation of calcium channel activity has been shown to modulate pain in clinical and experimental settings [2,4,5]. More recently, agents which modulate the activity of the calcium channel α2δ subunit have also been shown to exhibit experimentally and clinically important pain relief . However, a link between changes in voltage-gated calcium channel of DRG and the occurrence of postinflammatory hypersensitivity symptoms still has to be established. "
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Visceral pain is common symptom involved in many gastrointestinal disorders such as inflammatory bowel disease. The underlying molecular mechanisms remain elusive. We investigated the molecular mechanisms and the role for voltage gated calcium channel (VGCC) in the pathogenesis in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory hypersensitivity.
Using Agilent cDNA arrays, we found 172 genes changed significantly in dorsal root ganglia (DRG) of TNBS treated rats. Among these changed genes, Cav1.2 and Cav2.3 were significantly up-regulated. Then the RT-PCR and Western blot further confirmed the up-regulation of Cav1.2 and Cav2.3. The whole cell patch clamp recording of acutely dissociated colonic specific DRG neurons showed that the peak IBa density was significantly increased in colonic neurons of TNBS treated rats compared with control rats (−127.82 ± 20.82 pA/pF Vs −91.67 ± 19.02 pA/pF, n = 9, *P < 0.05). To distinguish the different type of calcium currents with the corresponding selective channel blockers, we found that L-type (−38.56 ± 3.97 pA/pF Vs −25.75 ± 3.35 pA/pF, n = 9, * P < 0.05) and R-type (−13.31 ± 1.36 pA/pF Vs −8.60 ± 1.25 pA/pF, n = 9, * P < 0.05) calcium current density were significantly increased in colonic DRG neurons of TNBS treated rats compared with control rats. In addition, pharmacological blockade with L-type antagonist (nimodipine) and R-type antagonist (SNX-482) with intrathecal injection attenuates visceral pain in TNBS induced inflammatory visceral hypersensitivity.
Cav1.2 and Cav2.3 in colonic primary sensory neurons play an important role in visceral inflammatory hyperalgesia, which maybe the potential therapeutic targets.
Molecular Pain 03/2013; 9(1):15. DOI:10.1186/1744-8069-9-15 · 3.65 Impact Factor
Available from: ncbi.nlm.nih.gov
- "Gabapentin is widely used for the treatment of chronic pain, and its effects have been proven in large numbers of animal pain models. In a study conducted by Field et al. , the systemic administration of gabapentin was shown to inhibit the thermal hyperalgesia and tactile allodynia induced by the incision of the plantaris muscle of a rat's hind paw. In other studies, with intrathecal injectins, formalin-induced pain responses were reduced only in the late phase [8-10], and synergistic effects were observed when gabapentin was administered intrathecally with other drugs such as N-methyl-D-aspartate (NMDA) receptor antagonists or non-NMDA receptor antagonists [10,11]. "
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ABSTRACT: Gabapentin is thought to exert an effect through the voltage-dependent calcium channel. Vitamin E is a widely known antioxidant which neutralizes the harmful effect of ROS which is considered to play a prominent role in various painful conditions. This study was therefore conducted to assess the antinociceptive effects of gabapentin and vitamin E and the interaction of these drugs in the modulation of pain in rats subjected to a formalin test.
Sprague-Dawley rats with a lumbar intrathecal catheter were tested for their paw flinches by 5% formalin injection after intrathecal injection of gabapentin or vitamin E. After obtaining dose-response curves for each drug, the effect of the combination was tested by the total dose fraction value and isobolographic analysis.
When a single drug was injected intrathecally, significant dose-dependent decreases in flinches were shown only in the late phase. ED(50) values of intrathecal gabapentin and vitamin E in the late phase were 75.3 ± 9.58 µg, and 17.56 ± 1.65 mg/kg respectively. The combination of gabapentin and vitamin E produced dose-dependent decreases in the number of flinches in both phases induced by the formalin test. The ED(50) value of the combination was lower than the theoretical additive values in the late phase, but did not show a significant difference with the theoretical additive value.
Gabapentin and vitamin E (by itself) have no antinociceptive effect in the early phase; however their combination has shown an antinociceptive effect. In addition, they show additive effects in the late phase of the formalin test.
Korean journal of anesthesiology 11/2012; 63(5):447-53. DOI:10.4097/kjae.2012.63.5.447
Available from: sciencedirect.com
- "In animal models of nociception, gabapentin reduced mechanical or thermal hyperalgesia  and incisional injury . Pretreatment with gabapentin also blocked the development of hyperalgesia, suggesting a preventive effect of gabapentin , and had a selective effect on the nociceptive process involving central sensitization . "
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Functional Endoscopic sinus surgery (FESS) is a delicate and time consuming procedure; it is performed routinely under general anesthesia. Hypotensive techniques should be employed for best visualization of operative field. Gabapentin is a structural analog of gamma amino butyric acid. The aim of this study was to determine the analgesic efficacy of gabapentin and its role in deliberate hypotension during and after FESS.Methods
Eighty patients ASA physical status I–II patients were scheduled to undergo elective FESS under general anesthesia. Patients were randomly assigned to one of two groups using a computer-generated table. Patients in the control group (40 patients) received oral placebo capsules and the study group (40 patients) patients received oral gabapentin (Conventin 400 mg; Evapharma Egypt) 1.2 g 1 h before surgery. Intraoperative, mean arterial blood pressure, infusion rates of the hypotensive agent (sodium nitroprusside) were recorded at 15 min interval. Assessments of pain, opioid usage, and side effects were performed at 1 h interval after arrival in the PACU.ResultsGabapentin group patients required significantly lower (p value <0.05) infusion rates and total doses of hypotensive agent (sodium nitroprusside) than the placebo group patients at all measured intervals. Postoperative assessment of pain scores revealed that gabapentin group recorded significantly lower mean values of VAS than the control group (p value <0.05).Conclusion
Oral gabapentin, 1200 mg decreased dose requirements of intraoperative hypotensive agent (sodium nitroprusside) and postoperative morphine. In addition, patients receiving gabapentin had suffered less from opioid side effects (nausea, vomiting and urinary retention) than those receiving placebo.
Egyptian Journal of Anaesthesia 07/2012; 28(3):189–192. DOI:10.1016/j.egja.2012.02.008
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