Korean J Physiol Pharmacol.  2010 Jun;14(3):191-198. 10.4196/kjpp.2010.14.3.191.

The Effects of Tramadol on Electroencephalographic Spectral Parameters and Analgesia in Rats

• Jang HS
• Jang IS
• Lee MG

• KMID: 2285402
• DOI: http://doi.org/10.4196/kjpp.2010.14.3.191

Abstract

The effects of different doses of tramadol on analgesia and electroencephalographic (EEG) spectral parameters were compared in rats. Saline or tramadol 5, 10, 20 or 40 mg/kg was administered. The degree of analgesia was evaluated by tail-flick latency, and the degree of seizure was measured using numerical seizure score (NSS). Additionally, band powers, median power frequency and spectral edge frequency 95 were measured to quantify the EEG response. All doses of tramadol produced spike-wave discharge. Tramadol significantly and dose-dependently increased the analgesia, but these effects did not correspond with the changes in the EEG spectral parameters. NSS significantly increased in the Tramadol 20 and 40 mg/kg treatment groups compared to the Control and TRA5 groups, and two rats given 40 mg/kg had convulsions. In conclusion, tramadol dose-dependently increased the analgesic effect, and the 10 mg/kg dose appears to be a reliable clinical dose for analgesia in rats, but dose-dependent increases in analgesia and seizure severity did not correlate with EEG spectral parameters.

Keyword

EEG; Spectrum; Analgesia; Seizure; Tramadol; Rat

MeSH Terms

Analgesia
Animals
Electroencephalography
Rats
Seizures
Tramadol
Tramadol

Figure

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  Fig. 1. Time course of analgesic effects in rats treated with tramadol. The rats (n=6) were intraperitoneally administered saline, and tramadol 5, 10, 20 and 40 mg/kg, respectively (group ‘Control’, ‘TRA5’, ‘TRA10’, ‘TRA20’ and ‘TRA40’). Analgesic effects were evaluated with 50°C hot-water tail-flick latency, and were expressed as a percentage of maximal possible effect (%MPE). Data were expressed as mean±S.D. Data were analyzed by two factor repeated measures ANOVA with time and treatment, and a Bonferroni test was used to analyze variables for time between groups. ∗p<0.05 when compared to Control group, #p<0.05 when compared to TRA5 group, +p<0.05 when compared to TRA10 group, and @p<0.05 when compared to TRA20 group.

• 

  Fig. 2. Time course of degree of seizure in rats treated with tramadol. The rats (n=6) were intraperitoneally administered saline, and tramadol 5, 10, 20 and 40 mg/kg, respectively (group ‘Control’, ‘TRA5’, ‘TRA10’, ‘TRA20’ and ‘TRA40’). The degree of seizure were evaluated with numerical seizure score (NSS), a modified Racine scale, from 0 to 5 as follows: 0, no response; 1, wet-dog shake/or behavioral arrest; 2, wet-dog shake, staring, pawing, clonic jerks; 3, bilateral forelimb clonus with rearing falling; 4, continuous grade 3 seizures for >30 min; and 5, death. Data were expressed as mean±S.D. Data were analyzed by two factor repeated measures ANOVA with time and treatment, and a Bonferroni test was used to analyze variables for time between groups. Statistical results were not marked in figure, but were described in text.

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  Fig. 3. Relative band powers on the medial prefrontal cortex (FC) in rats treated with tramadol. The rats (n=6) were intraperitoneally administered saline, and tramadol 5, 10, 20 and 40 mg/kg, respectively (group ‘Control’, ‘TRA5’, ‘TRA10’, ‘TRA20’ and ‘TRA40’). Data were expressed as mean±S.D. Data were analyzed by two factor repeated measures ANOVA with time and treatment, and a Bonferroni test was used to analyze variables for time between groups. Statistical results were not marked in figure, but were described in text.

• 

  Fig. 4. Relative band powers on the parietal cortex (PC) in rats treated with tramadol. The rats (n=6) were intraperitoneally administered saline, and tramadol 5, 10, 20 and 40 mg/kg, respectively (group ‘Control’, ‘TRA5’, ‘TRA10’, ‘TRA20’ and ‘TRA40’). Data were expressed as mean± S.D. Data were analyzed by two factor repeated measures ANOVA with time and treatment, and a Bonferroni test was used to analyze variables for time between groups. Only delta1 power showed significant changes by drug treatment in repeated measures ANOVA (F=2.8, p=0.046) but no significance in Bonferroni test.

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  Fig. 5. Electroencephalographic spectral parameters on the medial prefrontal cortex (FC) and the parietal cortex (PC) in rats treated with tramadol. The rats (n=6) were intraperitoneally administered saline, and tramadol 5, 10, 20 and 40 mg/kg, respectively (group ‘Control’, ‘TRA5’, ‘TRA10’, ‘TRA20’ and ‘TRA40’). The changes of spectral edge frequency 95 (SEF95) and median power frequency (MPF) between groups were not significant, except in MPF of FC. Data were expressed as mean±S.D. Data were analyzed by two factor repeated measures ANOVA with time and treatment, and a Bonferroni test was used to analyze variables for time between groups. Statistical results were not marked in figure, but were described in text.

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  Fig. 6. Raw electroencephalographic (EEG) spike-wave discharge (SWD) pattern in the medial prefrontal cortex (FC) and the parietal cortex (PC) corresponding with brief and phase movement in rats treated with intraperitoneal tramadol 40 mg/kg. The movement was evaluated with self-made movement-sensing-board, using a vibration sensor and acrylic board. The board was placed under the cage, and was used just for detecting twitching and convulsion. The raw EEG on the FC presented more discrete SWD pattern than on the PC.

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  Fig. 7. Raw electroencephalographic (EEG) spike-wave discharge (SWD) pattern in the medial prefrontal cortex (FC) and the parietal cortex (PC) corresponding with convulsive seizure in rats treated with intraperitoneal tramadol 40 mg/kg. Two rats treated with tramadol dose at 40 mg/kg showed convulsive seizures in the experiment 2.

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  Fig. 8. The number of spike-wave discharge on the medial prefrontal cortex (FC) and the parietal cortex (PC) in rats treated with tramadol. The rats (n=6) were intraperitoneally administered saline, and tramadol 5, 10, 20 and 40 mg/kg, respectively (group ‘Control’, ‘TRA5’, ‘TRA10’, ‘TRA20’ and ‘TRA40’). Data were expressed as mean±S.D. Data were analyzed by a Kruskal-Wallis H test followed by a Mann-Whitney test. ∗∗p<0.01 when compared to Control group, ##p<0.01 when compared to TRA5 group, ++p<0.01 when compared to TRA10 group, and @@p<0.01 when compared to TRA20 group.

Reference

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