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

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

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

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

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

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