Among trials designed to assess PONV as the primary end point, preoperative gabapentin was associated with a significantly reduced incidence of PONV (Fig. 2; RR = 0.60; 99% confidence interval [CI], 0.47–0.76, P < 0.0001; I 2 = 0%), nausea (Fig. 3; RR = 0.34; 99% CI, 0.17–0.65; P < 0.0001; I 2 = 0%), vomiting (Fig. 4; RR = 0.34; 99% CI, 0.16–0.73; P = 0.0002; I 2 = 0%), and rescue antiemetic administration (Fig. 5; RR = 0.52; 99% CI, 0.34–0.78; P < 0.0001; I 2 = 0%) within 24 hours when compared with controls. According to these results, the number needed to treat (NNT) to prevent PONV is 4.1. The NNT to prevent nausea is 4.9, NNT to prevent vomiting is 6.1, and NNT to prevent rescue antiemetic administration is 4.8.
Table 2 further illustrates the pooled effect of trials involving preoperative gabapentin excluding trials with repeat dosing, thiopental induction, and nitrous oxide administration. As shown in Table 2, there was similar antinausea and antivomiting efficacy in all subgroup analyses. Analysis of the pooled effects of preoperative gabapentin in trials involving abdominal, hysterectomy, and high-risk procedures yielded similar results.
Escalating 1-time doses of preoperative gabapentin were all associated with significant reductions in PONV (Table 3) aside from 1-time 1200 mg gabapentin, which resulted in a nonsignificant reduction in nausea (P = 0.10) compared with control. One-time 300 mg gabapentin administration resulted in significant heterogeneity (P < 0.0001; I 2 = 85%), which resolved when the study by Pandey et al.32 was excluded based on sensitivity analysis (I 2 = 1%).
When individual dosing regimens were reviewed, whereas pooled analysis of studies involving gabapentin dosing of 300 mg (RR = 2.91; 95% CI, 0.19–43.70; P = 0.44; P for heterogeneity = 0.005; I 2 = 87%), 600 mg (RR = 1.30; 95% CI, 0.94–1.81; P = 0.11; P for heterogeneity = 0.55; I 2 = 0%), and 900 mg (RR = 3.85; 95% CI, 0.51–24.96; P = 0.20; P for heterogeneity = 0.13; I 2 = 56%) resulted in no statistically significant sedation, preoperative gabapentin dosing of 1200 mg resulted in significant postoperative sedation (RR = 1.42; 95% CI, 1.04–1.95; P = 0.03; P for heterogeneity = 0.99; I 2 = 0%) compared with controls.
Although others have reported on the potential postoperative antiemetic effect of preoperative gabapentin, findings have been limited to isolated surgical settings such as abdominal surgery and hysterectomy,18,19 and reviews have been associated with significant heterogeneity. This has likely been due in large part to evaluation of studies where nausea and vomiting were secondary end points of included trials. Our review was tailored to address these limitations by evaluating the pooled effects of preoperative gabapentin among studies designed to investigate PONV as the primary end point. On the basis of the findings of the pooled analysis of involved trials, preoperative administration of gabapentin is shown to reduce postoperative nausea, vomiting, and rescue antiemetic requirements. Further analysis of all included trials that reported on PONV end points (primary or secondary) also resulted in a significant reduction in the incidence of PONV, nausea, vomiting, and rescue antiemetic requirement. This represents pooled data from the largest cohort of trials to date and suggests a significant role for preoperative gabapentin not only for alleviating postoperative pain but also for preventing PONV.
Reservation over the wide-spread adoption of the use of preoperative gabapentin is related to its central nervous system effects, namely potential excessive sedation and dizziness in the immediate postoperative period.65 Although our study did not show an association between gabapentin and various side effects, including dizziness/lightheadedness, headache, and dry mouth, we do report significant incidences of excessive postoperative sedation and somnolence. It is worth noting that, although a further analysis of sedation based on dosing schedule suggested the greatest impact with doses ≥1200 mg, these data should be interpreted with caution. Given the wide ranges of the associated CIs at smaller doses, we cannot entirely exclude these doses from causing similar rates of postoperative sedation. Unfortunately, only 2 studies reported directly on postanesthesia care unit (PACU) length of stay,31,60 and although neither study showed an association between gabapentin administration and prolonged PACU duration, there simply are not enough data available to make this assertion. Therefore, we cannot reliably comment on the significance of the observed postoperative somnolence effect or its clinical implication.
The majority of the primary end points of interest in the included studies involved the ability of preoperative gabapentin to both reduce postoperative pain scores and minimize the need for opioid rescue medications. Although the true mechanism mediating this effect is unknown, it is believed to be through action on the alpha2/delta subunit of voltage-sensitive calcium channels, thereby further inhibiting the downstream voltage-activated sodium channels and ultimate nociceptive signaling pathways.9,10 Interestingly, although upward titration of dosing appears to maximize pain-related efficacy in chronic pain such as diabetic neuropathy and postherpetic neuralgia, similar findings have not been consistently shown in the acute postoperative setting. At least 2 previous studies have reported a ceiling effect associated with a 1-time preoperative dose of either 600 or 900 mg, respectively.37,54 Above these thresholds, patients did not report improved pain scores compared with smaller doses. This phenomenon may be attributed to the proposed kinetics of gabapentin, whereby a saturable transport system may provide a dose-dependent absorption rather than a proportional one.66 In light of this potential ceiling effect of analgesia, coupled with our data that failed to show increased antiemetic efficacy with larger 1-time dosing of gabapentin, it would be reasonable for providers to consider moderate (600 mg) dosing schedules for preoperative gabapentin administration.
The actual mechanism by which gabapentin preempts nausea and vomiting remains a topic of debate. Previous studies have implicated a reduction in calcium signaling in the area postrema67,68 as well as a decreased tachykinin neurotransmission.69,70 Some have suggested a reduction in perioperative inflammation, thus reducing ileus and subsequent PONV.71 Still others explain the role of the drug in multimodal analgesia, thereby reducing perioperative opioid requirements and resulting in incidence of associated nausea and vomiting. A moderator analysis performed in a previous systematic review appears to refute this latter most theory,18 but it seems reasonable to conclude that some combination of the mechanisms above may be true.
This review was limited to preoperative gabapentin associated with general anesthesia in adults. Our review was not designed to assess the monitored anesthesia care with sedation, regional/neuraxial anesthetics, or pediatric populations. Other studies have been devoted to these topics separately.72–75 We also are unable to comment on the efficacy of administration of gabapentin in the immediate postoperative period although other studies suggest further benefit postoperatively as well.76 In addition, we cannot determine the efficacy of gabapentin on postdischarge PONV.77 There are limited numbers of studies that directly compare the known antiemetics and gabapentin on their ability to prevent PONV.26,28,62,78 Although previous results in this area favorably compare gabapentin with more traditional antiemetics, we cannot make overt statements regarding noninferiority compared with established antiemetics such as 5-hydroxytryptamine (5-HT),3 histaminic, or natural killer (NK)1 antagonists. Last, too few studies reported on PACU lengths of stay to reliably comment on the effect of potential excessive sedation in the postoperative period. This further alludes to the importance of additional high-quality controlled studies in this promising area.
Notably, our initial results among all included studies regarding overall nausea and sedation exhibited significant levels of heterogeneity. This effect was reversed after the exclusion of a single study.32 The disparate effect of this study was addressed in a previous review18 and is likely the result of using PONV as a secondary end point of the individual trial. Aside from heterogeneity, inclusion of this single trial did not affect the measure of our overall results.
The results of this study support the inclusion of preoperative gabapentin as part of the approach to prevent PONV. This conclusion is based not only on a meta-analysis of preoperative gabapentin with trials designed to investigate PONV as the primary end point but also on the review of the quantitative effect in trials regarding nausea and vomiting as secondary end points. In an era when comprehensive evidence-based protocols are being designed to both limit reliance upon opioids and maximize recovery, we would recommend the use of gabapentin to effectively improve both postoperative analgesic and antiemetic end points.
The authors would like to thank Blair Anton, Associate Director for Informationist Services of the William H. Welch Medical Library, for literature search assistance.
1. Apfel CC, Läärä E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999;91:693–700
2. Watcha MF, White PF. Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology. 1992;77:162–84
3. Habib AS, Chen YT, Taguchi A, Hu XH, Gan TJ. Postoperative nausea and vomiting following inpatient surgeries in a teaching hospital: a retrospective database analysis. Curr Med Res Opin. 2006;22:1093–9
4. Carroll NV, Miederhoff PA, Cox FM, Hirsch JD. Costs incurred by outpatient surgical centers in managing postoperative nausea and vomiting. J Clin Anesth. 1994;6:364–9
5. Golembiewski J, Chernin E, Chopra T. Prevention and treatment of postoperative nausea and vomiting. Am J Health Syst Pharm. 2005;62:1247–60
6. Gan TJ, Diemunsch P, Habib AS, Kovac A, Kranke P, Meyer TA, Watcha M, Chung F, Angus S, Apfel CC, Bergese SD, Candiotti KA, Chan MT, Davis PJ, Hooper VD, Lagoo-Deenadayalan S, Myles P, Nezat G, Philip BK, Tramèr MRSociety for Ambulatory Anesthesia. . Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014;118:85–113
7. Chandrakantan A, Glass PS. Multimodal therapies for postoperative nausea and vomiting, and pain. Br J Anaesth. 2011;107(suppl 1):i27–40
8. Moore RA, Wiffen PJ, Derry S, Toelle T, Rise AS. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2014;4
9. Fink K, Dooley DJ, Meder WP, Suman-Chauhan N, Duffy S, Clusmann H, Göthert M. Inhibition of neuronal Ca2+
influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology. 2002;42:229–36
10. Hurley RW, Cohen SP, Williams KA, Rowlingson AJ, Wu CL. The analgesic effects of perioperative gabapentin on postoperative pain: a meta-analysis. Reg Anesth Pain Med. 2006;31:237–47
11. Page AJ, Ejaz A, Spolverato G, Zavadsky T, Grant MC, Galante DJ, Wick EC, Weiss M, Makary MA, Wu CL, Pawlik TM. Enhanced recovery after surgery protocols for open hepatectomy–physiology, immunomodulation, and implementation. J Gastrointest Surg. 2015;19:387–99
12. Geltzeiler CB, Rotramel A, Wilson C, Deng L, Whiteford MH, Frankhouse J. Prospective study of colorectal enhanced recovery after surgery in a community hospital. JAMA Surg. 2014;149:955–61
13. Cruz FM, de Iracema Gomes Cubero D, Taranto P, Lerner T, Lera AT, da Costa Miranda M, da Cunha Vieira M, de Souza Fêde AB, Schindler F, Carrasco MM, de Afonseca SO, Pinczowski H, del Giglio A. Gabapentin for the prevention of chemotherapy-induced nausea and vomiting: a pilot study. Support Care Cancer. 2012;20:601–6
14. Guttuso T Jr, Roscoe J, Griggs J. Effect of gabapentin on nausea induced by chemotherapy in patients with breast cancer. Lancet. 2003;361:1703–5
15. Guttuso T Jr, Robinson LK, Amankwah KS. Gabapentin use in hyperemesis gravidarum: a pilot study. Early Hum Dev. 2010;86:65–6
16. Erol DD. The analgesic and antiemetic efficacy of gabapentin or ergotamine/caffeine for the treatment of postdural puncture headache. Adv Med Sci. 2011;56:25–9
17. Pandey CK, Priye S, Ambesh SP, Singh S, Singh U, Singh PK. Prophylactic gabapentin for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: a randomized, double-blind, placebo-controlled study. J Postgrad Med. 2006;52:97–100
18. Achuthan S, Singh I, Varthya SB, Srinivasan A, Chakrabarti A, Hota D. Gabapentin prophylaxis for postoperative nausea and vomiting in abdominal surgeries: a quantitative analysis of evidence from randomized controlled clinical trials. Br J Anaesth. 2015;114:588–97
19. Alayed N, Alghanaim N, Tan X, Tulandi T. Preemptive use of gabapentin in abdominal hysterectomy: a systematic review and meta-analysis. Obstet Gynecol. 2014;123:1221–9
20. Guttuso T Jr. Gabapentin’s anti-nausea and anti-emetic effects: a review. Exp Brain Res. 2014;232:2535–9
21. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12
22. Mohammadi SS, Seyedi M. Effects of gabapentin on early postoperative pain, nausea and vomiting in laparoscopic surgery for assisted reproductive technologies. Pak J Biol Sci. 2008;11:1878–80
23. Bashir F, Mohd K, Qazi S, Hashia AM. A randomized, double blind, placebo controlled study evaluating preventive role of gabapentin for PONV in patients undergoing laparoscopic cholecystectomy. JK Science. 2009;11:190–3
24. Khademi S, Ghaffarpasand F, Heiran HR, Asefi A. Effects of preoperative gabapentin on postoperative nausea and vomiting after open cholecystectomy: a prospective randomized double-blind placebo-controlled study. Med Princ Pract. 2010;19:57–60
25. Ajori L, Nazari L, Mazloomfard MM, Amiri Z. Effects of gabapentin on postoperative pain, nausea and vomiting after abdominal hysterectomy: a double blind randomized clinical trial. Arch Gynecol Obstet. 2012;285:677–82
26. Jahromi HE, Gholami M, Rezaei F. A randomized double-blinded placebo controlled study of four interventions for the prevention of postoperative nausea and vomiting in maxillofacial trauma surgery. J Craniofac Surg. 2013;24:e623–7
27. Misra S, Parthasarathi G, Vilanilam GC. The effect of gabapentin premedication on postoperative nausea, vomiting, and pain in patients on preoperative dexamethasone undergoing craniotomy for intracranial tumors. J Neurosurg Anesthesiol. 2013;25:386–91
28. Semira, Abbas S, Tandon VR, Bashir A, Kour K. A prospective, randomized, placebo-controlled trail comparing the effectiveness of gabapentin, ondansetron & dexamethasone in prevention of nausea & vomiting after laparoscopic cholecystectomy. JK Science. 2013;15:117–21
29. Dirks J, Fredensborg BB, Christensen D, Fomsgaard JS, Flyger H, Dahl JB. A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy. Anesthesiology. 2002;97:560–4
30. Dierking G, Duedahl TH, Rasmussen ML, Fomsgaard JS, Møiniche S, Rømsing J, Dahl JB. Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind trial. Acta Anaesthesiol Scand. 2004;48:322–7
31. Gilron I, Orr E, Tu D, O’Neill JP, Zamora JE, Bell AC. A placebo-controlled randomized clinical trial of perioperative administration of gabapentin, rofecoxib and their combination for spontaneous and movement-evoked pain after abdominal hysterectomy. Pain. 2005;113:191–200
32. Pandey CK, Priye S, Singh S, Singh U, Singh RB, Singh PK. Preemptive use of gabapentin significantly decreases postoperative pain and rescue analgesic requirements in laparoscopic cholecystectomy. Can J Anaesth. 2004;51:358–63
33. Rorarius MG, Mennander S, Suominen P, Rintala S, Puura A, Pirhonen R, Salmelin R, Haanpää M, Kujansuu E, Yli-Hankala A. Gabapentin for the prevention of postoperative pain after vaginal hysterectomy. Pain. 2004;110:175–81
34. Turan A, Karamanlioğlu B, Memiş D, Usar P, Pamukçu Z, Türe M. The analgesic effects of gabapentin after total abdominal hysterectomy. Anesth Analg. 2004;98:1370–3
35. Turan A, Karamanlioğlu B, Memiş D, Hamamcioglu MK, Tükenmez B, Pamukçu Z, Kurt I. Analgesic effects of gabapentin after spinal surgery. Anesthesiology. 2004;100:935–8
36. Ménigaux C, Adam F, Guignard B, Sessler DI, Chauvin M. Preoperative gabapentin decreases anxiety and improves early functional recovery from knee surgery. Anesth Analg. 2005;100:1394–9
37. Pandey CK, Navkar DV, Giri PJ, Raza M, Behari S, Singh RB, Singh U, Singh PK. Evaluation of the optimal preemptive dose of gabapentin for postoperative pain relief after lumbar diskectomy: a randomized, double-blind, placebo-controlled study. J Neurosurg Anesthesiol. 2005;17:65–8
38. Radhakrishnan M, Bithal PK, Chaturvedi A. Effect of preemptive gabapentin on postoperative pain relief and morphine consumption following lumbar laminectomy and discectomy: a randomized, double-blinded, placebo-controlled study. J Neurosurg Anesthesiol. 2005;17:125–8
39. Al-Mujadi H, A-Refai AR, Katzarov MG, Dehrab NA, Batra YK, Al-Qattan AR. Preemptive gabapentin reduces postoperative pain and opioid demand following thyroid surgery. Can J Anaesth. 2006;53:268–73
40. Bartholdy J, Hilsted KL, Hjortsoe NC, Engbaek J, Dahl JB. Effect of gabapentin on morphine demand and pain after laparoscopic sterilization using Filshie clips. A double blind randomized clinical trial. BMC Anesthesiol. 2006;6:12
41. Mikkelsen S, Hilsted KL, Andersen PJ, Hjortsø NC, Enggaard TP, Jørgensen DG, Hansen M, Henriksen J, Dahl JB. The effect of gabapentin on post-operative pain following tonsillectomy in adults. Acta Anaesthesiol Scand. 2006;50:809–15
42. Turan A, White PF, Karamanlioglu B, Memis D, Tasdogan M, Pamukçu Z, Yavuz E. Gabapentin: an alternative to the cyclooxygenase-2 inhibitors for perioperative pain management. Anesth Analg. 2006;102:175–81
43. Durmus M, Kadir But A, Saricicek V, Ilksen Toprak H, Ozcan Ersoy M. The post-operative analgesic effects of a combination of gabapentin and paracetamol in patients undergoing abdominal hysterectomy: a randomized clinical trial. Acta Anaesthesiol Scand. 2007;51:299–304
44. Koç S, Memis D, Sut N. The preoperative use of gabapentin, dexamethasone, and their combination in varicocele surgery: a randomized controlled trial. Anesth Analg. 2007;105:1137–42
45. Takmaz SA, Kaymak C, Pehlivan BS, Dikmen B. [Effect of preoperative 900 and 1200 mg single oral dose of gabapentin on postoperative pain relief and tramadol consumption in open cholecystectomy surgery]. Agri. 2007;19:32–8
46. Ghafari MH, Akrami M, Nouralishahi B, Sadegh A. Preoperative gabapentin or clonidine decreases postoperative pain and morphine consumption after abdominal hysterectomy. Res J BiolSci. 2009;4:458–63
47. Gilron I, Orr E, Tu D, Mercer CD, Bond D. A randomized, double-blind, controlled trial of perioperative administration of gabapentin, meloxicam and their combination for spontaneous and movement-evoked pain after ambulatory laparoscopic cholecystectomy. Anesth Analg. 2009;108:623–30
48. Sekhavat L, Zare F, Mojibian M. The postoperative analgesic effects of low-dose gabapentin in patients undergoing abdominal hysterectomy. S Afr J Obstet Gynecol. 2009;15:37–40
49. Sen H, Sizlan A, Yanarates O, Emirkadi H, Ozkan S, Dagli G, Turan A. A comparison of gabapentin and ketamine in acute and chronic pain after hysterectomy. Anesth Analg. 2009;109:1645–50
50. Bang SR, Yu SK, Kim TH. Can gabapentin help reduce postoperative pain in arthroscopic rotator cuff repair? A prospective, randomized, double-blind study. Arthroscopy. 2010;26:S106–11
51. Menda F, Köner O, Sayin M, Ergenoğlu M, Küçükaksu S, Aykaç B. Effects of single-dose gabapentin on postoperative pain and morphine consumption after cardiac surgery. J Cardiothorac Vasc Anesth. 2010;24:808–13
52. Srivastava U, Kumar A, Saxena S, Mishra AR, Saraswat N, Mishra S. Effect of preoperative gabapentin on postoperative pain and tramadol consumption after minilap open cholecystectomy: a randomized double-blind, placebo-controlled trial. Eur J Anaesthesiol. 2010;27:331–5
53. Ghai A, Gupta M, Hooda S, Singla D, Wadhera R. A randomized controlled trial to compare pregabalin with gabapentin for postoperative pain in abdominal hysterectomy. Saudi J Anaesth. 2011;5:252–7
54. Khan ZH, Rahimi M, Makarem J, Khan RH. Optimal dose of pre-incision/post-incision gabapentin for pain relief following lumbar laminectomy: a randomized study. Acta Anaesthesiol Scand. 2011;55:306–12
55. Ozgencil E, Yalcin S, Tuna H, Yorukoglu D, Kecik Y. Perioperative administration of gabapentin 1,200 mg day-1 and pregabalin 300 mg day-1 for pain following lumbar laminectomy and discectomy: a randomised, double-blinded, placebo-controlled study. Singapore Med J. 2011;52:883–9
56. Ucak A, Onan B, Sen H, Selcuk I, Turan A, Yilmaz AT. The effects of gabapentin on acute and chronic postoperative pain after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2011;25:824–9
57. Behdad S, Ayatollahi V, Bafghi AT, Tezerjani MD, Abrishamkar M. Effect of gabapentin on postoperative pain and operation complications: a randomized placebo controlled trial. West Indian Med J. 2012;61:128–33
58. Deniz MN, Sertoz N, Erhan E, Ugur G. Effects of preoperative gabapentin on postoperative pain after radical retropubic prostatectomy. J Int Med Res. 2012;40:2362–9
59. Frouzanfard F, Fazel MR, Abolhasani A, Fakharian E, Mousavi G, Moravveji A. Effects of gabapentin on pain and opioid consumption after abdominal hysterectomy. Pain Res Manag. 2013;18:94–6
60. Kinney MA, Mantilla CB, Carns PE, Passe MA, Brown MJ, Hooten WM, Curry TB, Long TR, Wass CT, Wilson PR, Weingarten TN, Huntoon MA, Rho RH, Mauck WD, Pulido JN, Allen MS, Cassivi SD, Deschamps C, Nichols FC, Shen KR, Wigle DA, Hoehn SL, Alexander SL, Hanson AC, Schroeder DR. Preoperative gabapentin for acute post-thoracotomy analgesia: a randomized, double-blinded, active placebo-controlled study. Pain Pract. 2012;12:175–83
61. Rimaz S, Alavi CE, Sedighinejad A, Tolouie M, Kavoosi S, Koochakinejad L. Effect of gabapentin on morphine consumption and pain after surgical debridement of burn wounds: a double-blind randomized clinical trial study. Arch Trauma Res. 2012;1:38–43
62. Siddiqui NT, Fischer H, Guerina L, Friedman Z. Effect of a preoperative gabapentin on postoperative analgesia in patients with inflammatory bowel disease following major bowel surgery: a randomized, placebo-controlled trial. Pain Pract. 2014;14:132–9
63. Khurana G, Jindal P, Sharma JP, Bansal KK. Postoperative pain and long-term functional outcome after administration of gabapentin and pregabalin in patients undergoing spinal surgery. Spine (Phila Pa 1976). 2014;39:E363–8
64. Kotsovolis G, Karakoulas K, Grosomanidis V, Tziris N. Comparison between the combination of gabapentin, ketamine, lornoxicam, and local ropivacaine and each of these drugs alone for pain after laparoscopic cholecystectomy: a randomized trial. Pain Pract. 2015;15:355–63
65. VanMeter SA, Kavanagh ST, Warren S, Barrett RW. Dose response of Gabapentin enacarbil versus placebo in subjects with moderate-to-severe primary restless legs syndrome: an integrated analysis of three 12-week studies. CNS Drugs. 2012;26:773–80
66. Chang CY, Challa CK, Shah J, Eloy JD. Gabapentin in acute postoperative pain management. Biomed Res Int. 2014;2014:631756
67. Felix R, Gurnett CA, De Waard M, Campbell KP. Dissection of functional domains of the voltage-dependent Ca2+
channel alpha2delta subunit. J Neurosci. 1997;17:6884–91
68. Stahl SM. Mechanism of action of alpha2delta ligands: voltage sensitive calcium channel (VSCC) modulators. J Clin Psychiatry. 2004;65:1033–4
69. Maneuf YP, Hughes J, McKnight AT. Gabapentin inhibits the substance P-facilitated K(+)-evoked release of [(3)H]glutamate from rat caudial trigeminal nucleus slices. Pain. 2001;93:191–6
70. Fehrenbacher JC, Taylor CP, Vasko MR. Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain. 2003;105:133–41
71. Dias JM, de Brito TV, de Aguiar Magalhães D, da Silva Santos PW, Batista JA, do Nascimento Dias EG, de Barros Fernandes H, Damasceno SR, Silva RO, Aragão KS, Souza MH, Medeiros JV, Barbosa AL. Gabapentin, a synthetic analogue of gamma aminobutyric acid, reverses systemic acute inflammation and oxidative stress in mice. Inflammation. 2014;37:1826–36
72. Mayell A, Srinivasan I, Campbell F, Peliowski A. Analgesic effects of gabapentin after scoliosis surgery in children: a randomized controlled trial. Paediatr Anaesth. 2014;24:1239–44
73. Tsai KC, Yang YL, Fan PC. Gabapentin for postoperative vomiting in children requiring posterior fossa tumor resection. Pediatr Neonatol. 2015;56:351–4
74. Kazak Z, Meltem Mortimer N, Sekerci S. Single dose of preoperative analgesia with gabapentin (600 mg) is safe and effective in monitored anesthesia care for nasal surgery. Eur Arch Otorhinolaryngol. 2010;267:731–6
75. Clarke H, Pereira S, Kennedy D, Andrion J, Mitsakakis N, Gollish J, Katz J, Kay J. Adding gabapentin to a multimodal regimen does not reduce acute pain, opioid consumption or chronic pain after total hip arthroplasty. Acta Anaesthesiol Scand. 2009;53:1073–83
76. Dauri M, Faria S, Gatti A, Celidonio L, Carpenedo R, Sabato AF. Gabapentin and pregabalin for the acute post-operative pain management. A systematic-narrative review of the recent clinical evidences. Curr Drug Targets. 2009;10:716–33
77. Wu CL, Berenholtz SM, Pronovost PJ, Fleisher LA. Systematic review and analysis of postdischarge symptoms after outpatient surgery. Anesthesiology. 2002;96:994–1003
78. Heidari M, Honarmand A, Safavi M, Chitsazi M, Khalighinejad F. Geranisetron versus gabapentin in preventing postoperative nausea and vomiting after middle ear surgery in adults: a double-blinded randomized clinical trial study. Adv Biomed Res. 2015;4:22