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The Role of NMDARs Ligands on Antinociceptive Effects of Pregabalin in the Tail Flick Test.

Meymandi MS, Keyhanfar F, Yazdanpanah O, Heravi G - Anesth Pain Med (2015)

Bottom Line: In NMDA pretreated groups, %MPE30 unlike %MPE75 decreased significantly compared to those of pregabalin.MK801 delayed the latency times in pretreated groups, but %MPE30 and %MPE75 did not change significantly compared to pregabalin alone.Our findings support the role of NMDARs in pregabalin antinociception, because the NMDAR agonist, unlike the antagonist, decreased the antinociceptive effect of pregabalin, even if tail flick is not an adequate pain assessment method in this regard.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

ABSTRACT

Background: Pregabalin as a new anticonvulsant has been used in different pain treatments.

Objectives: The aim of this study was to investigate the role of N-methyl-D-aspartate (NMDA) ligands in antinociceptive effect of pregabalin in mice using tail flick.

Materials and methods: NMDA (15 and 30 mg/kg) as an agonist or MK801 (0.02 and 0.05 mg/kg) as an antagonist were injected intraperitoneally either alone or 15 minutes before antinociceptive dose of pregabalin (100 mg/kg). Then the latency times and %MPE were measured in the tail flick assay during 75 minutes.

Results: NMDA and MK801 had no effects alone. NMDA pretreatment significantly decreased the latency times of pregabalin till 75(th) minutes. In NMDA pretreated groups, %MPE30 unlike %MPE75 decreased significantly compared to those of pregabalin. MK801 delayed the latency times in pretreated groups, but %MPE30 and %MPE75 did not change significantly compared to pregabalin alone.

Conclusions: Our findings support the role of NMDARs in pregabalin antinociception, because the NMDAR agonist, unlike the antagonist, decreased the antinociceptive effect of pregabalin, even if tail flick is not an adequate pain assessment method in this regard.

No MeSH data available.


Related in: MedlinePlus

Time course of latency times (a) and Maximum possible effect (%MPE) at 30th and 75th minutes (b) of pregabalin (100 mg/kg, i.p.), NMDA (15 and 30 mg/kg, i.p.) and their combination in the tail flick test. In the pg + NMDA15 and pg + NMDA30 groups, NMDA was injected 15 minutes before the pregabalin. The data are expressed as Mean ± SEM of eight mice. * P < 0.05 and ** P < 0.001 compared to controls. # P < 0.001 compared to pregabalin.
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fig23321: Time course of latency times (a) and Maximum possible effect (%MPE) at 30th and 75th minutes (b) of pregabalin (100 mg/kg, i.p.), NMDA (15 and 30 mg/kg, i.p.) and their combination in the tail flick test. In the pg + NMDA15 and pg + NMDA30 groups, NMDA was injected 15 minutes before the pregabalin. The data are expressed as Mean ± SEM of eight mice. * P < 0.05 and ** P < 0.001 compared to controls. # P < 0.001 compared to pregabalin.

Mentions: The time course of NMDA groups (NMDA 15 mg/kg and NMDA30 mg/kg) as well those of the pretreated groups (pg + NMDA15 and pg + NMDA30) were similar to the controls, and no significant differences were observed among them. The temporal variations and pattern of groups were not different (F4,212 = 0.65, P = 0.6), while the interaction between time and group resulted in a significant difference (F20,212 = 0.89, P = 0.000). The latency time of pregabalin alone was significantly more than all other groups (P < 0.001). However, the latency times of pretreated groups started to increase from 30 minutes and reached to the level of pregabalin alone after 75 minutes (Figure 3A).


The Role of NMDARs Ligands on Antinociceptive Effects of Pregabalin in the Tail Flick Test.

Meymandi MS, Keyhanfar F, Yazdanpanah O, Heravi G - Anesth Pain Med (2015)

Time course of latency times (a) and Maximum possible effect (%MPE) at 30th and 75th minutes (b) of pregabalin (100 mg/kg, i.p.), NMDA (15 and 30 mg/kg, i.p.) and their combination in the tail flick test. In the pg + NMDA15 and pg + NMDA30 groups, NMDA was injected 15 minutes before the pregabalin. The data are expressed as Mean ± SEM of eight mice. * P < 0.05 and ** P < 0.001 compared to controls. # P < 0.001 compared to pregabalin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644310&req=5

fig23321: Time course of latency times (a) and Maximum possible effect (%MPE) at 30th and 75th minutes (b) of pregabalin (100 mg/kg, i.p.), NMDA (15 and 30 mg/kg, i.p.) and their combination in the tail flick test. In the pg + NMDA15 and pg + NMDA30 groups, NMDA was injected 15 minutes before the pregabalin. The data are expressed as Mean ± SEM of eight mice. * P < 0.05 and ** P < 0.001 compared to controls. # P < 0.001 compared to pregabalin.
Mentions: The time course of NMDA groups (NMDA 15 mg/kg and NMDA30 mg/kg) as well those of the pretreated groups (pg + NMDA15 and pg + NMDA30) were similar to the controls, and no significant differences were observed among them. The temporal variations and pattern of groups were not different (F4,212 = 0.65, P = 0.6), while the interaction between time and group resulted in a significant difference (F20,212 = 0.89, P = 0.000). The latency time of pregabalin alone was significantly more than all other groups (P < 0.001). However, the latency times of pretreated groups started to increase from 30 minutes and reached to the level of pregabalin alone after 75 minutes (Figure 3A).

Bottom Line: In NMDA pretreated groups, %MPE30 unlike %MPE75 decreased significantly compared to those of pregabalin.MK801 delayed the latency times in pretreated groups, but %MPE30 and %MPE75 did not change significantly compared to pregabalin alone.Our findings support the role of NMDARs in pregabalin antinociception, because the NMDAR agonist, unlike the antagonist, decreased the antinociceptive effect of pregabalin, even if tail flick is not an adequate pain assessment method in this regard.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

ABSTRACT

Background: Pregabalin as a new anticonvulsant has been used in different pain treatments.

Objectives: The aim of this study was to investigate the role of N-methyl-D-aspartate (NMDA) ligands in antinociceptive effect of pregabalin in mice using tail flick.

Materials and methods: NMDA (15 and 30 mg/kg) as an agonist or MK801 (0.02 and 0.05 mg/kg) as an antagonist were injected intraperitoneally either alone or 15 minutes before antinociceptive dose of pregabalin (100 mg/kg). Then the latency times and %MPE were measured in the tail flick assay during 75 minutes.

Results: NMDA and MK801 had no effects alone. NMDA pretreatment significantly decreased the latency times of pregabalin till 75(th) minutes. In NMDA pretreated groups, %MPE30 unlike %MPE75 decreased significantly compared to those of pregabalin. MK801 delayed the latency times in pretreated groups, but %MPE30 and %MPE75 did not change significantly compared to pregabalin alone.

Conclusions: Our findings support the role of NMDARs in pregabalin antinociception, because the NMDAR agonist, unlike the antagonist, decreased the antinociceptive effect of pregabalin, even if tail flick is not an adequate pain assessment method in this regard.

No MeSH data available.


Related in: MedlinePlus