ACONITINE-INDUCED WRITHING : A METHOD FOR ASSESSMENT OF ANALGESIC ACTIVITY

T.N. BHALLA, J.N. SINHA, R.P. KOHLI AND K.P. BHARGAVA Departmentof Pharmacologyand Therapeutics,King George's Medical College, Lucknow-3, India Receivedfor publicationSeptember 26, 1968

Experimental methods for testing analgesic activity are based on the production of pain by mechanical, thermal, electrical or chemical stimuli. Most of these methods are unsuitable for assessment of acetyl salicylic acid (aspirin) type of analgesic activity. A painful syndrome commonly described as the writhing response has been induced by agents of diverse nature viz. phenylquinone (1 and 2), adrenaline (3), certain iodinated compounds (4) and bradykinin (5). The writhing response induced by bradykinin is generally recommended as a test for aspirin type of analgesic activity. The present report deals with the writhing response induced by intraperitoneal injection of aconitine and its suitability as a test for analgesic activity.

TABLE 1. Effect of oral pretreatment of drugs on aconitine-induced writhing in albino mice.

* Loss of righting reflex

** Data from 8 animals , 2 died. The characteristic pattern of the aconitine-induced writhing response was similar to that induced by bradykinin. It consisted of abdominal torsion, drawing up of hind legs to the abdominal wall, marked contractions of abdominal area and the periodic arching of the back to rub the abdominal wall on the glazed surface on which the mouse was kept. In control studies, the 100% effective dose of intraperitoneal aconitine for inducing the writhing response was found to be 2 pg per mice of weights ranging between 20-25 g. The typical response appears within 5 minutes of aconitine injection and persists for a period of 20-35 minutes. The following drugs were examined for their anti-writhing activity: acetyl salicylic acid, sodium salicylate, butazolidine, morphine, chlorpromazine, imipramine, methaqualone, diphenylhydantoin sodium (Dilantin), mephenesin and phenoxybenzamine. Groups of ten albino mice each were employed for every dose of the drugs tested. The animals were fed the test drug one half hour before the intraperitoneal injection of the 100% effective dose of aconitine (2 pg) and observed for 30 minutes. The PD 50 of acetyl salicylic acid, sodium salicylate, butazolidine, morphine and chlorpromazine was determined by the method of Finney (6). The protective effect of methaqualone, Dilantin, imipramine, mephenesin, phenoxybenzamine in pharmacologically effective doses was also determined. The results of the study are summarized in Table 1. The writhing response induced by aconitine, in comparision to that of bradykinin, is quicker to appear, persists for a longer period and is consistantly observed at 2 pg dose level. Analgesic agents selectively blocked the aconitine induced writhing response. Chlorpromazine prevented the response in doses which produced loss of righting reflex. Other CNS active agents did not modify the response. The fact that aconitine induced writhing response is more consistent than that of bradykinin and is selectively blocked by the commonly employed analgesic agents, clearly indicates its superiority as a test for analgesic activity. REFERENCES 1) SIEGMUND,E., CADMUS,R. AND Hu, G.: Proc. Soc. exp. Biol. Med. 95, 729 (1957) ; 2) EMELE,J.F., SHANAMAN,J. AND WARRAN, M.: J. Pharmac. exp. Ther. 134, 206 (1961) ; 3) MATSUMOTO,C. AND NICKANDER,R.: Fedn Proc. 26, 619 (1967) ; 4) WENDE, C.V. AND MARGOLIN,S.: Fedn Proc. 15, 494 (1956) ; 5) EMELE,J.F. AND SHANAMON,J.: Proc. Soc. exp. Biol. Med. 114, 680 (1963) ; 6) FINNEY, D.T.: Probit Analysis, 2nd Ed., Cambridge University Press