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RESEARCH LETTER
Year : 2005  |  Volume : 37  |  Issue : 1  |  Page : 37-38
 

Study of the antinociceptive effect of neem leaf extract and its interaction with morphine in mice


Department of Pharmacology, Medical College, Baroda - 390 001, Gujarat, India

Correspondence Address:
Jagat D Bhatt
Department of Pharmacology, Medical College, Baroda - 390 001, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.13854

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How to cite this article:
Patel J P, Hemavathi K G, Bhatt JD. Study of the antinociceptive effect of neem leaf extract and its interaction with morphine in mice. Indian J Pharmacol 2005;37:37-8

How to cite this URL:
Patel J P, Hemavathi K G, Bhatt JD. Study of the antinociceptive effect of neem leaf extract and its interaction with morphine in mice. Indian J Pharmacol [serial online] 2005 [cited 2019 Jul 16];37:37-8. Available from: http://www.ijp-online.com/text.asp?2005/37/1/37/13854


Sir,

Azadirachta indica (Neem), an indigenous drug, has been reported to be an useful hypolipidaemic, hypoglycemic, immunostimulant, hepatoprotective, antiinflammatory and antifertility agent.[1] Several analgesic drugs have been reported to be very useful out of which the most potent group for control of moderate to severe pain is the opioid analgesics like morphine but these exhibit a lot of adverse effects.[2] The objectives of the present work were (i) to study the antinociceptive effects of neem leaf extract and its interaction with morphine and (ii) to delineate the probable site of action of neem leaf extract using an opioid antagonist, naloxone.

Albino mice (Haffkine strain) of either sex (25-35 g) were used throughout the study. All the animals were maintained in the departmental animal house at ambient temperature of 25-35° C with food and water available ad libitum. The animals were divided into the following groups (n=6 for each group).

Group 1: Receiving saline (control).
Groups 2, 3, 4 and 5: Receiving four different doses of NLE (3.12, 6.25,12.5 and 50 mg/ kg).
Groups 6 and 7: Receiving two different doses of morphine (0.5 and 1 mg/ kg).
Group 8: Receiving combined treatment consisting of NLE (3.12 mg/ kg) and morphine (0.5 mg/ kg).
GROUP 9: Receiving naloxone (1 mg/ kg).
GROUP 10: Receiving combined treatment consisting of NLE (50 mg/ kg) and naloxone (1 mg/ kg).

In all the groups, either saline or the drugs were administered subcutaneously 15 min prior to the antinociceptive test. However, naloxone was administered 25 minutes prior to the antinociceptive test i.e.10 min prior to NLE administration. Antinociceptive activity was measured using analgesiometer by tail-flick method[3] using radiant heat from an electric source. The tail flick latencies were obtained before and after drugs administration with cut-off time as 10 seconds. For the comparison between two pairs, unpaired Student's 't ' test was employed. One-way ANOVA followed by Dunnett's multiple comparisons was used to analyze the data. P values < 0.05 were considered statistically significant. All the values were expressed in terms of mean±SEM.

Animals treated with either saline or NLE in a dose of 3.12 mg/kg showed no significant change in tail-flick latency at intervals of 15, 30, 60, 120 and 180 min as compared to the control value at 0 minutes [Table - 1]. Administration of higher doses of NLE produced dose-dependent increase in the tail-flick latency [Table - 1].

Lower dose (0.5 mg/kg) of morphine did not produce any significant change in the tail-flick latency till 180 minutes. With a higher dose (1 mg/kg), the antinociceptive effect started from 15 min onwards, with the peak effect at 30 min [Table - 1].

The combination, consisting of a low dose of NLE (3.12 mg/kg) and a low dose of morphine (0.5 mg/kg) produced a significant increase in the tail-flick latency at all the time intervals as compared to the corresponding value at 0 min, with the peak effect at 60 min [Table - 1].

Naloxone at the dose of 1 mg/kg showed no significant increase in the tail-flick latency; however, it showed significant hyperalgesia at intervals of 15, 30 and 60 min with peak effect at 60 min [Table - 1]. Combined treatment consisting of NLE (50 mg/ kg) and naloxone (1 mg/ kg) produced no significant change in the tail-flick latency at all the time intervals except hyperalgesia seen at 60 min [Table - 1]. Hence naloxone pretreatment antagonized the antinociceptive effect of NLE suggesting the involvement of endogenous opioid peptides or opioid receptors in the mediation of the antinociceptive response of NLE.

The results of the present study revealed the antinociceptive effect of NLE in the pain model of the tail-flick test due to thermal stimulation. The present findings confirm those of previous investigators, who reported dose-dependent analgesic activity of NLE in mice and rats using various models of analgesia.[4],[5] Neem leaves have been reported to relieve pain by opioidergic as well as other mechanisms.[4]

These results could thus have a potential clinical implication. Thus patients can benefit from relief of pain, using either morphine or NLE alone or their combination with lesser adverse effects.

 
 » References Top

1.Khosla P, Bhanwra S, Singh J, Srivastava RK. Antinociceptive activity of A. indica (Neem) in rats. Indian J Pharmacol 2000;32:372-4.  Back to cited text no. 1    
2.Barth H, Durra S, Giertz H, Goroll D, Flohe L. Long term administration of the centrally acting analgesic did not induce dependence or tolerance. Abstract No 439. Pain 1987:231.  Back to cited text no. 2    
3.D'Armour FE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther 1941;72:74-9.  Back to cited text no. 3    
4.Khanna N, Goswami M, Sen P, Ray A. Antinociceptive action of A. indica (neem) in mice: Possible mechanisms involved. Indian J Exp Biol 1995;33:848-50.  Back to cited text no. 4  [PUBMED]  
5.Witkin LB, Heubner CF, O'Keete E, Spitatalitta P, Plummer AJ. Pharmacology of 2-aminoindone hydrochloride (SU-8629): A potent non-narcotic analgesic. J Pharmacol Exp Ther 1961;133:400-8.  Back to cited text no. 5    


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