Evaluation of analgesic activity of sodium valproate and ethanolic extract of Vitex negundo in experimental analgesic models in wistar rats

Ravi K. Sori, Basavaraj Poojar, Nandan Hodlur, Amod Tilak, Rupa Korde, Priya Gandigawad


Background: NSAIDs and opioids are commonly prescribed medications to relieve pain of multiple aetiologies with no effect on the level of consciousness of the patient. They interfere with the mode of transmission of the pain message. A widely prescribed antiepileptic drug, sodium valproate has been used in various non-epileptic conditions like migraine prophylaxis and in the treatment of bipolar disorder because of the multiple mechanisms by which it acts. Vitex negundo has been investigated for antipyretic, analgesic, anti-inflammatory, anticonvulsant, hepatoprotective and bronchial relaxant. Very few studies have been done to evaluate its analgesic activity and no study was done on analgesic activity with the combination of modern drug. The more important point to be noted is that Vitex negundo is a natural product and therefore unlikely to cause adverse effects when compared to the traditional drugs used to treat pain. The aim of the present study was to evaluate of analgesic activity of sodium valproate and docosahexaenoic in experimental analgesic models in wistar rats.

Methods: For analgesic activity, a total of 36 adult Wistar albino rats were taken and divided into six groups of six rats each. Group I was control (distil water 1ml/kg), Group II received intraperitoneal injection of diclofenac sodium (10mg/kg), Group III, IV were injected intraperitoneal sodium valproate 200, 400mg/kg with distil water respectively and Group V, VI were given sodium valproate 200, 400mg/kg (intraperitoneal) plus EEVN 400mg/kg (orally) respectively. Analgesic activity was assessed using hot plate, tail flick and acetic acid writhing models.

Results: Present study revealed that sodium valproate at higher doses (400mg/kg) used either alone along with EEVN (400mg/kg) showed statistically significant analgesic activity in comparison to control in various experimental models for assessing pain.

Conclusions: Combination of sodium valproate along with EEVN has shown promising analgesic activity.


Analgesia, Antiepileptic, Acetic acid writhing, Hot plate, Tail flick

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Negus SS, Vanderah TW, Brandt MR, Bilsky EJ, Becerra L, Borsook D. Preclinical assessment of candidate analgesic drugs: recent advances and future challenges. J Pharmacol Experimental Therapeut. 2006 Nov 1;319(2):507-14.

Le Bars D, Gozariu M, Cadden SW. Animal models of nociception. Pharmacological Rev. 2001 Dec 1;53(4):597-652.

Bhalerao PP, Pawade RB, Joshi S. Evaluation of analgesic activity of Dashamoola formulation by using experimental models of pain. Indian J Basic Appl Med Res. 2015;4(3):245-55.

Kunder SK, Bairy LK, Arivazhahan A. Effect of sodium valproate and docosahexaenoic acid on pain in rats. J Clin Diagnostic Res. 2017 Mar;11(3):FF05.

DeVane CL. Pharmacokinetics, drug interactions, and tolerability of valproate. Psychopharmacol Bull. 2003;37:25-42.

Kim HJ, Rowe M, Ren M, Hong JS, Chen PS, Chuang DM. Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action. J Pharmacol Experimental Therapeut. 2007 Jun 1;321(3):892-901.

Tirumalasetty J, Ubedulla S, Chandrasekhar N, Kishan PV, Rasamal K. Evaluation of antipyretic activity of alcoholic extract of Vitex nigundo leaves in PGE1 induced pyrexia model in Albino rats. J Chem Pharm Res. 2012;4(6):3015-9.

8. Telang RS, Chatterjee S, Varshneya C. Studies on analgesic and anti-inflammatory activities of Vitex negundo Linn. Indian J Pharmacol. 1999;31:363-6.

Utpalendu J, Chattopadhyay RN, Badri PS. Preliminary studies on anti-inflammatory activity of Zingiber officinale Rosc., Vitex negundo Linn and Tinospora cordifolia (willid) Miers in albino rats. Indian J Pharmacol. 1999 May 1;31(3):232.

Ravishankar B, Bhaskaran NR, Sasikala CK. Pharmacological evaluation of Vitex negundo (Nirgundi) leaves. Bull Med Ethno Bot Res. 1985;6(1):72-92.

Gupta M, Mazumder UK, Bhawal SR. CNS activity of Vitex negundo Linn in mice. Indian J Exp Biol. 1999;37:143-6.

Percival M. Understanding the natural management of pain and inflammation. Clin Nutr Insights. 1999;4(30):1-5.

Raza M, Dhariwal MA, Ageel AM, Qureshi S. Evaluation of the antiinflammatory activity of sodium valproate in rats and mice. Gen Pharmacol. 1996;27(8):1395-400.

Maniyar YA, Sriraj D. Evaluation of anti-inflammatory activity of ethanolic extract of vitex negundo flowers in experimental animals. Indian J Pharma Pharmacol. 2017;4(4):172-5.

Gao J, Wang X, Sun H, Cao Y, Liang S, Wang H, et al. Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model. Int J Developmental Neurosci. 2016 Apr 1;49:67-78.

Richette P, Bardin T. Gout. Lancet. 2010;375:318-28.

Jaiswal SR, Sontakke SD. Experimental evaluation of analgesic and anti-inflammatory activity of simvastatin and atorvastatin. Indian J Pharmacol. 2012;44(4):475-79.

Manirujjaman, Sultana F, Md. Haque IU, Md. Chowdhury R, Md. Hossain T. In vivo assay of analgesic activity of methanolic and petroleum ether extracts of Vitex negundo leaves. J Pharma Biol Sci. 2013;7(3):56-9.

Witkin LB, Heubner CF, Galdi F, O'keefe E, Spitaletta P, Plummer AJ. Pharmacology of 2-amino-indane hydrochloride (Su-8629): a potent non-narcotic analgesic. J Pharmacol Exp Therapeut. 1961 Sep 1;133(3):400-8.

Mesdjian E, DeFeudis FV, Valli M, Jadot G, Mandel P. Antinociceptive action of sodium valproate in the mouse. Gen Pharmacol. 1983;14(6):697-99.

Koster R, Anderson M, de Beer EJ. Acetic acid for analgesic screening. Fed Proc. 1959;18:138.

Taber RI, Greenhouse DD, Rendell JK, Irwin S. Agonist and antagonist interactions of opioids on acetic acid-induced abdominal stretching in mice. J Pharmacol Exp Ther. 1969;169(1):29-38.

Schumacher GA, Goodell H, Hardy JD, Wolff HG. Uniformity of the pain threshold in man. Science. 1940 Aug 2;92(2379):110-2.

Wolff HG, Hardy JD, Goodell H. Studies on pain. Measurement of the effect of morphine, codeine, and other opiates on the pain threshold and an analysis of their relation to the pain experience. J Clin Investigation. 1940 Jul 1;19(4):659-80.