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SP06-52: Analgesic & Neuroprotective Effect of S-adenosyl L-Methionine (SAM) on Nitro-glycerine (NTG) induced Migraine in Albino Mice

Poster Presenter

Rachana Atul Salvi

Post Graduate Student
Seth GS Medical College & KEM Hospital
India

Objectives

Inflammatory pathways and oxidative stress are involved in migraine. SAM exerts analgesic, anti-inflammatory, anti-oxidant effect and reverses DNA methylation during chronic pain. Hence we evaluated analgesic and neuroprotective effect of SAM on NTG induced Migraine in Swiss Albino Mice.

Method

Post standardisation, mice (n=46) received NTG on day 1 (acute), 3,5,7,9,11 (chronic). SAM (150,250 mg/kg), sumatriptan for acute & propranolol for chronic model was given for 11 days. Hot plate & two chamber tests were done at 0,2 & 4hrs post NTG. On 11th day, MDA, TNFa & DNA methylation was done.

Results

Behavioral tests for acute model of migraine were performed 2hr and 4hr after administration of NTG (10mg/kg i.p) as an inducing agent on day-1. Behavioral tests were hot plate and two-chamber box, where recovery from migraine was assessed by increased latency to lick hind paw & increased time spent in light chamber respectively. There was significant recovery in mice for SAM 250mg/kg group versus disease control (DC) for latency to lick hind paw (14.8±0.8 vs 7.5±.0.8, p<0.05) & increased time spent in light chamber (242.17±48.21 vs 160.3±25.82, p<0.05) respectively in acute model at 2 hour. In both these behavioral tests, the results of above mentioned variables for SAM 250 were comparable to positive control sumatriptan 0.6mg/kg i.p at 2hr (14.83±2.48 vs 18.83±1.21 & 242.17±48.21 vs 294.5±47.5, p>0.05). However, there was no significant difference in study groups for both these tests at 4hrs. The chronic model of migraine was established by induction of NTG (10mg/kg i.p) on days 1,3,5,7,9,11. Behavioral tests readings were taken at baseline (0hrs) on all the above mentioned days. In this chronic model at the end of day 11, recovery was assessed with variables of hot plate test & two chambered box test for both SAM 150 & SAM 250 (12.4±0.6, 14.7±0.6 vs 8.7±0.6 & 210.38±6.8,232.5±6.8 vs 161.72±6.8, p<0.05). The results for both doses of SAM were comparable to positive control propranolol 20mg/kg i.p. (12.4±0.6, 14.7±0.6 vs 15.5±0.6 & 210.38±6.8,232.5±6.8 vs 350.3±6.8, p>0.05) There was significant decrease in the MDA as well as TNFa levels in both SAM 150 and SAM 250 groups vs DC(23.7±0.2, 18.3±0.4 vs 32.4±0.3 & 161±1.1, 146±1.9 vs 200.8±22.1 ,p<0.001). The decrease in MDA and TNFa levels for SAM in both doses was comparable to propranolol (23.7±0.2, 18.3±0.4 vs 12.9±1 & 161±1.1, 146±1.9 vs 139.2±1.4 p>0.05). The 5-Methylcytosine levels corresponding to DNA methylation in brain cells showed significant rise only for SAM 250 mg/kg (6.41±0.08 vs 5.43±0.05 ,p<0.001).

Conclusion

Hot plate and 2-chambered box tests determine pain and aura respectively. They were performed for both acute and chronic migraine model, where variables assessed were latency in hind paw licking & time spent in light chamber for hot plate & 2-chambered box respectively. Both tests showed recovery by significant increase in latency time for hind paw licking & increased time spent in light box for SAM 250 group at 2hrs & not 4hrs on day-1 post NTG induction (Acute migraine model). Both tests showed, there was no improvement in SAM 150 group at 2 & 4hrs as they were not significant as compared to DC. To conclude, higher dose of SAM has potential analgesic role for acute migraine therapy at 2hrs since SAM 250 was comparable to positive control sumatriptan. Behavioural tests for chronic migraine showed significant increase in latency time for hind paw licking & increased time spent in light box for SAM 150 & 250 group. Hence, SAM shows analgesic effect in chronic migraine therapy as both doses of SAM were comparable to positive control propranolol. The oxidative stress to DNA, lipids & inflammation seen in migraine were assessed by DNA methylation, MDA and TNFa respectively. These tests were performed on day-11 for chronic migraine model. MDA and TNFa markers increase in oxidative stress and inflammation respectively. There was a significant decrease in both of them in SAM 150 & 250 group. Hence, there is potential antioxidative and anti-inflammatory effect of SAM as both doses were comparable to propranolol. The 5-Methylcytosine levels corresponding to DNA methylation in brain cells decrease due to oxidative DNA damage in chronic migraine. The levels showed significant rise only for SAM 250 mg/kg. Thus, SAM has a potential role in chronic migraine due to its antioxidant neuroprotective and anti-inflammatory action. Hence, our study concludes SAM has neuro-protective & analgesic effects in migraine.