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Title: Evaluation of Analgesic and anti-inflammatory effects of four exploratory daily doses and a single high dose of Vitamin D3in Two Animal Models of Pain in Swiss Albino Mice: An active controlled, single blinded study

Running Title: Evaluation of analgesic and anti-inflammatory effects of Vitamin D3 using two validated animal pain models

Abstract

INTRODUCTION: Vitamin-D3 use for pain and inflammation is highly debated. This study was undertaken to compare 3 daily doses (15/30/60 µg/kg) and single high-dose of vitamin-D3 (260µg/kg) to standard drugs viz tramadol and diclofenac in two most commonly resorted pain-models.

MATERIALS AND METHODS: For both models, Swiss-albino mice. Analgesic activity was evaluated by hot-plate and writhing-test on baseline (day 0), day 7,14 and 21. Latency-period for jump/hind-paw licks, MPE% and time-onset-of-writhes, mean number-of-writhes, %inhibition-writhes were respective parameters evaluated. Tramadol and diclofenac were used as positive-control respectively and 0.25%CMC as vehicle(negative) control. Data were described as mean±SD. Inferential analysis was done using RM/ANOVA/ Kruskal-Wallis/Friedman’s-ANOVA, followed by Tukey-Kramer multiple-comparison tests.

RESULTS: On day-7, groups recorded positive antinociceptive-effect over vehicle-control. MPE% values of 60µ/kg were higher than tramadol at 60-and 90-minutes. On day-14 of hot-plate test, significant analgesic-effect was observed in 15µ/kg at 60-minutes. 60µ/kg recorded highest MPE% sustained at 60-minutes, higher than tramadol. On day-21 dose of 260µ/kg showed significantly raised value at 0thminute and highest MPE% at 30-minute. 30µ/kg recorded values higher than tramadol at all time-intervals. On day 14, groups receiving 30-and 60µ/kg showed significant analgesic effect in writhing-test.

CONCLUSION: In comparison to tramadol and diclofenac; 15-,30-,60-and 260µ/kg did not produce statistically significant analgesic-effect on day 7-,14-and 21. However, on daily-dosing 60 and 260µ/kg of vitamin-D3 showed significant analgesic-effect in hot-plate test when compared to baseline and control. Secondly, 15-and 30µ/kg, contrary to our expectation, on instances exhibited irritant effects.

Keywords:

Covid-19, Diclofenac, Hot-plate, NSAIDs, Opioids, Writhing-test