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Anesthesiology:
Clinical Investigations

A Randomized Study of the Effects of Single-dose Gabapentin versus Placebo on Postoperative Pain and Morphine Consumption after Mastectomy

Dirks, Jesper M.D.*; Fredensborg, Birgitte B. M.D.†; Christensen, Dennis M.D., Ph.D.‡; Fomsgaard, Jonna S. M.D.†; Flyger, Henrik M.D., Ph.D.§; Dahl, Jørgen B. M.D., Ph.D.†

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Abstract

Background: The anticonvulsant gabapentin has proven effective for neuropathic pain in three large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models involving central neuronal sensitization. It has been suggested that central neuronal sensitization may play an important role in postoperative pain. The aim of the study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in patients undergoing radical mastectomy.
Methods: In a randomized, double-blind, placebo-controlled study, 70 patients received a single dose of oral gabapentin (1,200 mg) or placebo 1 h before surgery. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 4 h postoperatively. Pain was assessed on a visual analog scale at rest and during movement, and side effects were assessed on a four-point verbal scale 2 and 4 h postoperatively.
Results: Thirty-one patients in the gabapentin group and 34 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from a median of 29 (interquartile range, 21–33) to 15 (10–19) mg (P < 0.0001). Pain during movement was reduced from 41 (31–59) to 22 (10–38) mm at 2 h postoperatively (P < 0.0001) and from 31 (12–40) to 9 (3–34) mm at 4 h postoperatively (P = 0.018). No significant differences between groups were observed with regard to pain at rest or side effects.
Conclusion: A single dose of 1,200 mg oral gabapentin resulted in a substantial reduction in postoperative morphine consumption and movement-related pain after radical mastectomy, without significant side effects. These promising results should be validated in other acute pain models involving central neuronal sensitization.
THE anticonvulsant gabapentin is widely used for treatment of chronic pain and has reduced neuropathic pain in three large placebo-controlled clinical trials. 1–3 Despite intensive investigation, the molecular mechanism of action of gabapentin remains unsettled (for review, see Taylor et al.4). Experimental studies have demonstrated antihyperalgesic effects of gabapentin in models involving central neuronal sensitization, without affecting acute pain transmission. 5 In healthy volunteers, gabapentin enhanced the effect of morphine in the cold pressor test, 6 reduced primary mechanical allodynia in acute inflammation following a thermal injury, 7 and reduced secondary hyperalgesia following sensitization with combined heat and capsaicin, without affecting acute nociceptive thresholds. 8
It has been suggested that central neuronal sensitization may amplify postoperative pain, although the relative contribution of various pain mechanisms to postoperative pain has not been established. 9 The hypothesis of the present study was that gabapentin, due to its potent antihyperalgesic effects, may reduce postoperative pain.
The objective of the study was therefore to investigate the effect of a single dose of 1,200 mg oral gabapentin on morphine consumption and pain in the immediate postoperative period after unilateral radical mastectomy and axillary dissection. The design and description of the present trial adhere to the Consolidated Standards of Reporting Clinical Trials statement. 10
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Materials and Methods

Participants
Women aged 18–75 yr who were scheduled for unilateral radical mastectomy with axillary dissection were eligible for the study. Patients were not included if they were unable to cooperate, had known allergy to gaba-pentin or morphine, a history of drug or alcohol abuse, chronic pain or daily intake of analgesics or corticosteroids, diabetes, or impaired kidney function. Patients with an intake of NSAIDs or paracetamol 24 h prior to operation or an intake of antacids 48 h prior to operation were also excluded from the study. Patients were recruited from the Department of Breast Surgery, Herlev University Hospital (Herlev, Denmark), during the period December 2000 to October 2001.
Written informed consent was obtained from all patients, and the study was approved by the Regional Ethics Committee (Herlev, Denmark) and The Danish National Health Board (Copenhagen, Denmark).
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Interventions
Patients received 0.125 mg sublingual triazolam and 1,200 mg oral gabapentin or placebo 1 h before surgery. General anesthesia was induced with 1.5–2.5 mg/kg propofol, and infusion of 1 μg/kg remifentanil for 1 min. A laryngeal mask was inserted. Anesthesia was maintained with infusion of propofol at the discretion of the anesthetist, and a fixed infusion of 0.4 μg · kg−1 · min−1 remifentanil. Hypotension was treated with isotonic sodium chloride, 6% hetastarch in saline, and/or 5 mg ephedrine intravenously in incremental doses, in order to preserve systolic blood pressure above 90 mmHg.
The infusions of propofol and remifentanil were terminated at skin closure; 0.5 mg alfentanil was administered intravenously to all patients, who were then transferred to the postoperative care unit. Postoperative pain treatment consisted of patient-controlled intravenous morphine (Abbott Pain Management Provider; Abbott, Virum, Denmark), 2.5-mg bolus, 10 min lock-out time. Additional morphine, 2.5 mg intravenously, was administered by a nurse observer, if requested by the patient, during the lock-out period. Ondansetron, 4 mg intravenously, was administered on patient request. No other medications were administered during the 4-h observation period.
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Outcomes and Assessments
The primary outcome measure was total morphine consumption from 0 to 4 h postoperatively. Secondary outcome measures were pain at rest and during mobilization from the supine to the sitting position, and side effects: nausea, somnolence, lightheadedness, dizziness, headache, visual disturbances, and vomiting.
Before surgery, all patients were instructed in the use of patient-controlled analgesia and the visual analog scale (0 mm = no pain, 100 mm = worst pain imaginable). To ensure equal assessment methods, all assessors were instructed carefully by the primary investigator (J. Dirks) before participating in the study.
Total morphine consumption was recorded from 0 to 4 h postoperatively. Pain scores (visual analog scale) at rest and during mobilization were assessed by the patients at 2 and 4 h after surgery.
Side effects were rated on a four-point verbal scale (none, mild, moderate, severe) at 2 and 4 h after surgery. The number of patients vomiting, as well as use of antiemetics, was recorded.
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Study Population Size
Based on preliminary results from our department, the anticipated morphine requirement was 25 mg/4 h (SD = 10). We considered a 30% reduction in morphine consumption to be clinical relevant. With a type 1 error of 5% and a power of 90%, 32 patients were required in each study group.
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Blinding
The study was randomized, double-blind, and placebo-controlled. Study medication was prepared by the hospital pharmacy into identical capsules containing either 300 mg gabapentin, or placebo. Study medication was marked with the name of the project, the investigator's name, and consecutive numbers according to a computer-generated block randomization schedule prepared by the hospital pharmacy. Patients were enrolled by the same investigators who also performed the assessments. Participants were assigned consecutively to their group according to their number. No person was aware of group assignment until all 70 patients had been included and assessments were completed.
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Statistical Methods
Data are presented as medians with lower and upper quartiles. Variables were evaluated with the Mann-Whitney rank sum test for unpaired data. All significant P values were corrected with the Bonferroni test for repeated measurements. P < 0.05 was considered statistically significant. Calculations were performed using SPSS 10.0 for Windows (SPPS, Chicago, IL). The statistical analysis was performed by the investigators.
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Results

Fig. 1
Fig. 1
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From December 6, 2000 to October 5, 2001, 87 consecutive patients who fulfilled the inclusion criterions were considered for inclusion in the study (fig. 1). Seventeen patients were not included: six patients did not want to participate; eight patients were not included due to lack of time of the investigators; one patient had paracetamol the morning before surgery; one patient claimed that she was not able to swallow the study medication; one patient had breast implants, which should be removed before mastectomy.
Seventy patients were included in the study; however, five of these were subsequently excluded, four in the gabapentin and one in the placebo group. In the gaba-pentin group, one patient was unable to swallow the study medication, one patient was reoperated due to bleeding 3 h after the primary operation, one patient received medication other than prescribed in the study protocol, and one patient was not connected properly to the patient-controlled analgesia device. In the placebo group, one patient was excluded due to incorrect connection to the patient-controlled analgesia device. Thus, data from 65 patients, 31 of 35 in the gabapentin group and 34 of 35 in the placebo group, were included and analyzed.
Table 1
Table 1
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Baseline demographic and clinical characteristics of each group appear in table 1. No significant differences were observed between groups.
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Morphine Consumption
Total morphine consumption was reduced from 29 (21–23) mg in the placebo group to 15 (10–19) mg in the gabapentin group (P < 0.0001).
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Pain Scores
Fig. 2
Fig. 2
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Pain at rest was reduced from 33 (23–44) mm in the placebo group to 19 (10–43) mm in the gabapentin group at 2 h postoperatively, and from 12 (9–30) to 7 (1–18) mm at 4 h postoperatively. These reductions were not statistically significant (P = 0.094 and P = 0.084, respectively, after Bonferroni correction;fig. 2A). Pain during movement was reduced from 41 (31–59) mm in the placebo group to 22 (10–38) mm in the gabapentin group at 2 h postoperatively (P < 0.0001), and from 31 (12–40) to 9 (3–34) mm at 4 h postoperatively (P = 0.018, after Bonferroni correction;fig. 2B).
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Side Effects
Table 2
Table 2
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The incidence of side effects appears in table 2. The most common side effect was somnolence, which was typically described as mild to moderate. Lightheadedness and dizziness were also common and were also described as mild to moderate, whereas other adverse effects were rare. No significant differences were observed in any outcome between groups (P > 0.05 for all observations;table 2). One patient in each group vomited; eight patients in the gabapentin group and five patients in the placebo group received ondansetron (P > 0.05).
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Discussion

A single dose of 1,200 mg oral gabapentin administered preoperatively resulted in a 50% reduction in postoperative morphine consumption and in a substantial reduction in movement-related pain 2 and 4 h after radical mastectomy. Pain at rest was also reduced by gabapentin, but this reduction was not statistically significant. No significant differences in side effects were observed between gabapentin and placebo in this study, with patients evaluated in the first 4 h after a general anesthetic.
Gabapentin has demonstrated potent antihyperalgesic properties in preclinical and clinical studies, without affecting acute nociception. 5,8 In experimental studies, gabapentin suppressed experimentally induced hyperalgesia. 11–13 Intrathecal administration reduced tactile allodynia after incision, 14 enhanced pain behavior in rats after formalin induced pain, 15 and reduced mechanical hyperalgesia in a rat model of postoperative pain. 16 In a recent clinical study, gabapentin demonstrated a substantial inhibitory effect not only on the development of but also on established secondary allodynia and hyperalgesia resulting from sensitization of the skin with heat and capsaicin in volunteers. 8 The magnitude of this effect was comparable with the effect observed with the potent opioid remifentanil in another study, 17 but in contrast, without affecting acute nociceptive thresholds 8 and with only moderate side effects. The observed selective effect on allodynia and hyperalgesia 8 is comparable with results with ketamine, but without the psychomimetic side effects observed with this NMDA receptor antagonist. 18
It has been suggested that central neuronal sensitization may play an important role not only in chronic pain states such as neuropathic pain, but also in postoperative pain. 9 The relative contribution of various pain mechanisms to postoperative pain has, however, not been established. A number of “antihyperalgesic” methods and drugs, including “preemptive analgesia”19 and NMDA receptor antagonists, 20–22 have been evaluated in order to reduce the central neuronal hyperexcitability, which theoretically may amplify postoperative pain. Results, however, have been discordant and not clinically impressive.
So far, the potential effect of gabapentin on acute, postoperative pain has not been evaluated in clinical studies. Pregabalin is an analog of the inhibitory neurotransmitter γ-aminobutyric acid. In a randomized, double-blind, placebo-controlled, parallel-group trial, 300 mg pregabalin was compared to placebo and 400 mg ibuprofen using a dental pain model. 23 Results showed that there were statistically significant differences in pain relief, pain intensity difference, and pain relief intensity difference between the 300-mg pregabalin group and placebo. Consequently, pregabalin appears to have significant analgesic properties in the third molar extraction model.
The mechanism of action of gabapentin in the present study could be explained by prevention or reduction of the development of central neuronal hyperexcitability induced by the surgical procedure. This hypothesis is further supported by the fact that only evoked pain during movement that is during augmented afferent transmission to dorsal horn neurons was significantly decreased, in contrast to pain at rest, where effects were less definite and not statistically significant. It should be noted, though, that pain at rest in the placebo group was only modest, especially at 4 h postoperatively, which makes it difficult to demonstrate an analgesic effect of any intervention.
Another explanation to the observed effects of gaba-pentin may be that intraoperative remifentanil increased postoperative pain and morphine requirement due to induction of acute opioid tolerance 24 and that gabapentin may modulate this tolerance, as observed with NMDA receptor antagonists. 25 In a recent study, however, no clinical evidence of induction of acute opioid tolerance after remifentanil-based anesthesia was observed, 26 and this explanation remains speculative.
No significant differences in side effects were observed between placebo and gabapentin in the present study, despite the fact that a rather large dose of gaba-pentin was administered. It should be noted that patients were assessed in the immediate postoperative period, from 0 to 4 h after surgery and a general anesthetic, and that this may have masked side effects due to gabapentin. Furthermore, our study was not powered to investigate side effects of gabapentin per se. Dizziness and somnolence have been demonstrated to be the most common adverse events of gabapentin in previous controlled studies of chronic pain. 1–3 The situation in the postoperative period is quite different from that of chronic pain states, however, and gabapentin may have a favorable side effect profile in the postoperative period, compared with, for example, opioids.
In conclusion, this is the first clinical study to demonstrate an analgesic or antihyperalgesic effect of gabapentin in somatic, postoperative pain. These promising results should be validated in other surgical procedures, with multiple dosing and prolonged follow-up. In addition to its potential effects on postoperative pain, gabapentin and analogs may prove valuable as tools in the study of acute pain mechanisms. 27
The authors thank Dorte Langhoff, Pharm.D. (Copenhagen County Hospital Pharmacy, Herlev, Denmark), for expert assistance in preparing the study medication.
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American Surgeon
Invited commentary - Pain after mastectomy and breast reconstruction
Vadivelu, N; Schreck, M; Lopez, J; Kodumudi, G; Narayan, D
American Surgeon, 74(4): 285-296.

Aesthetic Plastic Surgery
Combined Preoperative Use of Celecoxib and Gabapentin in the Management of Postoperative Pain
Parsa, AA; Sprouse-Blum, AS; Jackowe, DJ; Lee, M; Oyama, J; Parsa, FD
Aesthetic Plastic Surgery, 33(1): 98-103.
10.1007/s00266-008-9230-y
CrossRef
Anesthesia and Analgesia
Gabapentin Use in Pediatric Spinal Fusion Patients: A Randomized, Double-Blind, Controlled Trial
Rusy, LM; Hainsworth, KR; Nelson, TJ; Czarnecki, ML; Tassone, JC; Thometz, JG; Lyon, RM; Berens, RJ; Weisman, SJ
Anesthesia and Analgesia, 110(5): 1393-1398.
10.1213/ANE.0b013e3181d41dc2
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Lancet
Anaesthesia, surgery, and challenges in postoperative recovery
Kehlet, H; Dahl, JB
Lancet, 362(): 1921-1928.

Anesthesia and Analgesia
The analgesic effects of gabapentin after total abdominal hysterectomy
Turan, A; Karamanlioglu, B; Memis, D; Usar, P; Pamukcu, Z; Ture, M
Anesthesia and Analgesia, 98(5): 1370-1373.
10.1213/01.ANE.0000108964.70485.B2
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European Archives of Oto-Rhino-Laryngology
The effectiveness of gabapentin on post-tonsillectomy pain control
Jeon, EJ; Park, YS; Park, SS; Lee, SK; Kim, DH
European Archives of Oto-Rhino-Laryngology, 266(): 1605-1609.
10.1007/s00405-008-0897-0
CrossRef
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Preemptive use of gabapentin significantly decreases postoperative pain and rescue analgesic requirements in laparoscopic cholecystectomy
Pandey, CK; Priye, S; Singh, S; Singh, U; Singh, RB; Singh, PK
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 51(4): 358-363.

Anesthesia and Analgesia
Preoperative gabapentin decreases anxiety and improves early functional recovery from knee surgery
Menigaux, C; Adam, F; Guignard, B; Sessler, DI; Chauvin, M
Anesthesia and Analgesia, 100(5): 1394-1399.
10.1213/01.ANE.0000152010.74739.B8
CrossRef
Anesthesia and Analgesia
Gabapentin: An alternative to the cyclooxygenase-2 inhibitors for perioperative pain management
Turan, A; White, PF; Karamanlioglu, B; Memis, D; Tasdogan, M; Pamukcu, Z; Yavuz, E
Anesthesia and Analgesia, 102(1): 175-181.
10.1213/01.ane.0000184824.43411.63
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Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Review article: The role of anticonvulsant drugs in postoperative pain management: a bench-to-bedside perspective
Gilron, I
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 53(6): 562-571.

Anesthesia and Analgesia
Pregabalin: Its pharmacology and use in pain management
Gajraj, NM
Anesthesia and Analgesia, 105(6): 1805-1815.
10.1213/01.ane.0000287643.13410.5e
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British Journal of Anaesthesia
Acute pain: combination treatments and how we measure their efficacy
McQuay, HJ; Poon, KH; Derry, S; Moore, RA
British Journal of Anaesthesia, 101(1): 69-76.
10.1093/bja/aen108
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European Archives of Oto-Rhino-Laryngology
Single dose of preoperative analgesia with gabapentin (600 mg) is safe and effective in monitored anesthesia care for nasal surgery
Kazak, Z; Mortimer, NM; Sekerci, S
European Archives of Oto-Rhino-Laryngology, 267(5): 731-736.
10.1007/s00405-009-1175-5
CrossRef
Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie
Tumour pain therapy
Ohnesorge, H; Siebrecht, D; Gleim, M
Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie, 38(6): 403-+.

Acta Anaesthesiologica Scandinavica
Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: A randomized, double-blind trial
Dierking, G; Duedahl, TH; Rasmussen, ML; Fomsgaard, JS; Moiniche, S; Romsing, J; Dahl, JB
Acta Anaesthesiologica Scandinavica, 48(3): 322-327.

Current Opinion in Investigational Drugs
The mechanism of action of gabapentin in neuropathic pain
Baillie, JK; Power, I
Current Opinion in Investigational Drugs, 7(1): 33-39.

British Journal of Hospital Medicine
Gabapentin for postoperative pain relief
Varadan, R; Holding, J
British Journal of Hospital Medicine, 67(8): 444.

Current Drug Targets
Gabapentin and Pregabalin for the Acute Post-operative Pain Management. A Systematic-narrative Review of the Recent Clinical Evidences
Dauri, M; Faria, S; Gatti, A; Celidonio, L; Carpenedo, R; Sabato, AF
Current Drug Targets, 10(8): 716-733.

Proceedings of the 7Th Biennial Congress Asian & Oceanic Society of Regional Anesthesia & Pain Medicine
Recent advances in the treatment of neuropathic pain
Khor, KE
Proceedings of the 7Th Biennial Congress Asian & Oceanic Society of Regional Anesthesia & Pain Medicine, (): 99-106.

Regional Anesthesia and Pain Medicine
Management of perioperative pain in patients chronically consuming opioids
Carroll, IR; Angst, MS; Clark, JD
Regional Anesthesia and Pain Medicine, 29(6): 576-591.
10.1016/j.rapm.2004.06.009
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CNS Drugs
Perioperative pain management
Pyati, S; Gan, TJ
CNS Drugs, 21(3): 185-211.

Anesthesia and Analgesia
Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety
Tiippana, EM; Hamunen, K; Kontinen, VK; Kalso, E
Anesthesia and Analgesia, 104(6): 1545-1556.
10.1213/01.ane.0000261517.27532.80
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Neurotherapeutics
Use of Antiepileptic drugs for nonepileptic conditions: psychiatric disorders and chronic pain
Ettinger, AB; Argoff, CE
Neurotherapeutics, 4(1): 75-83.

Journal of Pharmacological Sciences
Mechanisms of the antinociceptive action of gabapentin
Cheng, JK; Chiou, LC
Journal of Pharmacological Sciences, 100(5): 471-486.
10.1254/jphs.CR0050020
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Pharmacology Biochemistry and Behavior
Gabapentin enhances the analgesic response to morphine in acute model of pain in male rats
Meymandi, MS; Sepehri, GR; Mobasher, M
Pharmacology Biochemistry and Behavior, 85(1): 185-189.
10.1016/j.pbb.2006.07.037
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Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Brief review: Perioperative management of the patient with chronic non-cancer pain
Hadi, I; Morley-Forster, PK; Dain, S; Horrill, K; Moulin, DE
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 53(): 1190-1199.

Journal of Molecular Neuroscience
Effect of gabapentin on c-Fos expression in the CNS after paw surgery in rats
Kazi, JA; Gee, CF
Journal of Molecular Neuroscience, 32(3): 228-234.
10.1007/s12031-007-0048-x
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Biochemical Society Transactions
When pain after surgery doesn't go away ...
Burke, S; Shorten, GD
Biochemical Society Transactions, 37(): 318-322.
10.1042/BST0370318
CrossRef
Prehospital Emergency Care
Pain Management in Current Combat Operations
Black, IH; McManus, J
Prehospital Emergency Care, 13(2): 223-227.
10.1080/10903120802290778
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Expert Review of Anticancer Therapy
Current challenges in cancer pain management: does the WHO ladder approach still have relevance?
Burton, AW; Hamid, B
Expert Review of Anticancer Therapy, 7(): 1501-1502.
10.1586/14737140.7-11.1501
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Anesthesia and Analgesia
The median effective dose of preemptive gabapentin on postoperative morphine consumption after posterior lumbar spinal fusion
Van Elstraete, AC; Tirault, M; Lebrun, T; Sandefo, I; Bernard, JC; Polin, B; Vally, P; Mazoit, JX
Anesthesia and Analgesia, 106(1): 305-308.
10.1213/01.ane.0000297417.05690.31
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Anesthesia and Analgesia
The Analgesic Effect of Gabapentin as a Prophylactic Anticonvulsant Drug on Postcraniotomy Pain: A Prospective Randomized Study
Ture, H; Sayin, M; Karlikaya, G; Bingol, CA; Aykac, B; Ture, U
Anesthesia and Analgesia, 109(5): 1625-1631.
10.1213/ane.0b013e3181b0f18b
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Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Cardiopulmonary bypass does not affect plasma concentration of preoperatively administered gabapentin
Parlow, J; Gilron, I; Milne, B; Dumerton-Shore, D; Orr, E; Phelan, R
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 57(4): 337-342.
10.1007/s12630-010-9269-5
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CNS Drugs
Gabapentin
Gilron, I
CNS Drugs, 17(): 983-984.

Anesthesia and Analgesia
The comparative evaluation of gabapentin and carbamazepine for pain management in Guillain-Barre syndrome patients in the intensive care unit
Pandey, CK; Raza, M; Tripathi, M; Navkar, DV; Kumar, A; Singh, UK
Anesthesia and Analgesia, 101(1): 220-225.
10.1213/01.ANE.0000152186.89020.36
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Russian Journal of Physical Chemistry A
Effects of Gabapentin on Different Neuronal Populations in the Dorsal-Root Ganglia of Rats with Streptozotocin-Induced Diabetes Mellitus
Romanenko, SV; Kostyuk, PG; Kostyuk, EP
Russian Journal of Physical Chemistry A, 83(): 100-110.

Current Medical Research and Opinion
Pharmacological treatment of chronic pain - the need for CHANGE
Varrassi, G; Muller-Schwefe, G; Pergolizzi, J; Oronska, A; Morlion, B; Mavrocordatos, P; Margarit, C; Mangas, C; Jaksch, W; Huygen, F; Collett, B; Berti, M; Aldington, D; Ahlbeck, K
Current Medical Research and Opinion, 26(5): 1231-1245.
10.1185/03007991003689175
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Anesthesia and Analgesia
The effects of intrathecal gabapentin on spinal morphine tolerance in the rat tail-flick and paw pressure tests
Hansen, C; Gilron, I; Hong, M
Anesthesia and Analgesia, 99(4): 1180-1184.
10.1213/01.ANE.0000130383.874.38.A9
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Javma-Journal of the American Veterinary Medical Association
Prevention of central sensitization and pain by N-methyl-D-aspartate receptor antagonists
Pozzi, A; Muir, WW; Traverso, F
Javma-Journal of the American Veterinary Medical Association, 228(1): 53-60.

Life Sciences
Role of spinal voltage-dependent calcium channel alpha(2)delta-1 subunit in the expression of a neuropathic pain-like state in mice
Narita, M; Nakajima, M; Miyoshi, K; Narita, M; Nagumo, Y; Miyatake, M; Yajima, Y; Yanagida, K; Yamazaki, M; Suzuki, T
Life Sciences, 80(): 2015-2024.
10.1016/j.lfs.2007.02.045
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British Journal of Anaesthesia
Gabapentin: a multimodal perioperative drug?
Kong, VKF; Irwin, MG
British Journal of Anaesthesia, 99(6): 775-786.
10.1093/bja/aem316
CrossRef
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Effects of nabilone, a synthetic cannabinoid, on postoperative pain
Beaulieu, P
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 53(8): 769-775.

Pain
Multiple dose gabapentin attenuates cutaneous pain and central sensitisation but not muscle pain in healthy volunteers
Segerdahl, M
Pain, 125(): 158-164.
10.1016/j.pain.2006.05.008
CrossRef
CNS Drugs
Opinion and evidence in neurology and psychiatry
[Anon]
CNS Drugs, 17(1): 63-70.

Anesthesia and Analgesia
The analgesic effects of gabapentin in monitored anesthesia care for ear-nose-throat surgery
Turan, A; Memis, D; Karamanlioglu, B; Yagiz, R; Pamukcu, Z; Yavuz, E
Anesthesia and Analgesia, 99(2): 375-378.

Anesthesia and Analgesia
Multimodal analgesia with gabapentin and local anesthetics prevents acute and chronic pain after breast surgery for cancer
Fassoulaki, A; Triga, A; Melemeni, A; Sarantopoulos, C
Anesthesia and Analgesia, 101(5): 1427-1432.
10.1213/01.ANE.0000180200.11626.8E
CrossRef
Anesthesia and Analgesia
A single preoperative dose of gabapentin (800 milligrams) does not augment postoperative analgesia in patients given interscalene brachial plexus blocks for arthroscopic shoulder surgery
Adam, F; Menigaux, C; Sessler, DI; Chauvin, M
Anesthesia and Analgesia, 103(5): 1278-1282.
10.1213/01.ane.0000237300.78508.f1
CrossRef
Daru-Journal of Faculty of Pharmacy
Intraventricular gabapentin is antinociceptive and enhances systemic morphine antinociception in rat tail flick test
Shamsi, MM; Mobasher, M; Sepehri, G; Haghdoost, A; Babaie, M
Daru-Journal of Faculty of Pharmacy, 15(4): 212-217.

Journal of Cellular Biochemistry
Pregabalin and gabapentin inhibit substance P-induced NF-kappa B activation in neuroblastoma and glioma cells
Park, S; Ahn, ES; Han, DW; Lee, JH; Min, KT; Kim, H; Hong, YW
Journal of Cellular Biochemistry, 105(2): 414-423.
10.1002/jcb.21837
CrossRef
Javma-Journal of the American Veterinary Medical Association
Clinical evaluation of perioperative administration of gabapentin as an adjunct for postoperative analgesia in dogs undergoing amputation of a forelimb
Wagner, AE; Mich, PM; Uhrig, SR; Hellyer, PW
Javma-Journal of the American Veterinary Medical Association, 236(7): 751-756.

British Journal of Anaesthesia
Effect of oral gabapentin on postoperative epidural analgesia
Turan, A; Kaya, G; Karamanlioglu, B; Pamukcu, Z; Apfel, CC
British Journal of Anaesthesia, 96(2): 242-246.
10.1093/bja/aei294
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Regional Anesthesia and Pain Medicine
The analgesic effects of perioperative gabapentin on postoperative pain: A meta-analysis
Hurley, RW; Cohen, SP; Williams, KA; Rowlingson, AJ; Wu, CL
Regional Anesthesia and Pain Medicine, 31(3): 237-247.
10.1016/j.rapm.2006.01.005
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Acta Anaesthesiologica Scandinavica
The effect of gabapentin on post-operative pain following tonsillectomy in adults
Mikkelsen, S; Hilsted, KL; Andersen, PJ; Hjortso, NC; Enggaard, TP; Jorgensen, DG; Hansen, M; Henriksen, J; Dahl, JB
Acta Anaesthesiologica Scandinavica, 50(7): 809-815.
10.1111/j.1399-6579.2006.01057.x
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American Journal of Ophthalmology
Oral gabapentin for the treatment of postoperative pain after photorefractive keratectomy
Nissman, SA; Tractenberg, RE; Babbar-Goel, A; Pasternak, JF
American Journal of Ophthalmology, 145(4): 623-629.
10.1016/j.ajo.2007.11.012
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Anesthesia and Analgesia
Perioperative Pregabalin Improves Pain and Functional Outcomes 3 Months After Lumbar Discectomy
Burke, SM; Shorten, GD
Anesthesia and Analgesia, 110(4): 1180-1185.
10.1213/ANE.0b013e3181cf949a
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Clinical Chemistry
Procedure for the monitoring of gabapentin with 2,4,6-trinitrobenzene sulfonic acid derivatization followed by HPLC with ultraviolet detection
Juenke, JM; Brown, PI; McMillin, GA; Urry, FM
Clinical Chemistry, 49(7): 1198-1201.

Proceedings of the 7Th Biennial Congress Asian & Oceanic Society of Regional Anesthesia & Pain Medicine
Management of regional pain syndromes in patients undergoing reoperation of the painful limb: Applying new techniques to old problems
Khor, KE
Proceedings of the 7Th Biennial Congress Asian & Oceanic Society of Regional Anesthesia & Pain Medicine, (): 91-97.

Pain
Gabapentin for the prevention of postoperative pain after vaginal hysterectomy
Rorarius, MGF; Mennander, S; Suominen, P; Rintala, S; Puura, A; Pirhonen, R; Salmelin, R; Haanpaa, M; Kujansuu, E; Yli-Hankala, A
Pain, 110(): 175-181.
10.1016/j.pain.2004.03.023
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Journal of Palliative Medicine
Regional cancer pain syndromes
Chang, VT; Janjan, N; Jain, S; Chau, C
Journal of Palliative Medicine, 9(6): 1435-1453.

Expert Review of Neurotherapeutics
Medical management of acute pain in patients with chronic pain
De Pinto, M; Cahana, A
Expert Review of Neurotherapeutics, 12(): 1325-1338.
10.1586/ERN.12.123
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Pain Research & Management
Effects of gabapentin on pain and opioid consumption after abdominal hysterectomy
Frouzanfard, F; Fazel, MR; Abolhasani, A; Fakharian, E; Mousavi, G; Moravveji, A
Pain Research & Management, 18(2): 94-96.

Experimental and Clinical Psychopharmacology
Randomized, Placebo-Controlled Pilot Trial of Gabapentin During an Outpatient, Buprenorphine-Assisted Detoxification Procedure
Sanders, NC; Mancino, MJ; Gentry, WB; Guise, JB; Bickel, WK; Thostenson, J; Oliveto, AH
Experimental and Clinical Psychopharmacology, 21(4): 294-302.
10.1037/a0033724
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Seminars in Respiratory and Critical Care Medicine
Evaluation and Treatment of Pain in Critically Ill Adults
Joffe, AM; Hallman, M; Gelinas, C; Herr, DL; Puntillo, K
Seminars in Respiratory and Critical Care Medicine, 34(2): 189-200.
10.1055/s-0033-1342973
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Reduction of Verbal Pain Scores after Anterior Cruciate Ligament Reconstruction with 2-Day Continuous Femoral Nerve Block: A Randomized Clinical Trial
Williams, BA; Kentor, ML; Vogt, MT; Irrgang, JJ; Williams, JP; Bottegal, MT; West, RV; Harner, CD; Fu, FH
Anesthesiology, 104(2): 315-327.

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Analgesic Treatment after Laparoscopic Cholecystectomy: A Critical Assessment of the Evidence
Bisgaard, T
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Anesthesiology, 98(6): 1521-1522.

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Perioperative Management of Acute Pain in the Opioid-dependent Patient
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Anesthesiology, 101(1): 212-227.

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Is Gabapentin a “Broad-spectrum” Analgesic?
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Anesthesiology, 97(3): 537-539.

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Intrathecal Gabapentin Enhances the Analgesic Effects of Subtherapeutic Dose Morphine in a Rat Experimental Pancreatitis Model
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Chronic Oral Gabapentin Reduces Elements of Central Sensitization in Human Experimental Hyperalgesia
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The evolution of pain management in the critically ill trauma patient: Emerging concepts from the global war on terrorism
Malchow, RJ; Black, IH
Critical Care Medicine, 36(7): S346-S357.
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Differential Effects of Neuropathic Analgesics on Wind-up-like Pain and Somatosensory Function in Healthy Volunteers
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Rowbotham, MC
The Clinical Journal of Pain, 22(5): 425-429.
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The Clinical Journal of Pain, 26(5): 381-385.
10.1097/AJP.0b013e3181cb406e
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Gabapentin action and interaction on the antinociceptive effect of morphine on visceral pain in mice
Meymandi, M; Sepehri, G
European Journal of Anaesthesiology (EJA), 25(2): 129-134.
10.1017/S0265021507001226
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Prabhakar, H; Arora, R; Bithal, PK; Rath, GP; Dash, HH
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Turan, A; Karamanloglu, B; Memis, D; Hamamcoglu, MK; Tükenmez, B; Pamukçu, Z; Kurt, I
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Effect of preoperative gabapentin on postoperative pain and tramadol consumption after minilap open cholecystectomy: a randomized double-blind, placebo-controlled trial
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