MEASUREMENT OF THE EFFECT ON THE PAIN THRESHOLD OF ACETYLSALICYLIC ACID, ACETANILID, ACETOPHENETIDIN, AMINOPYRINE, ETHYL ALCOHOL, TRICHLORETHYLENE, A BARBITURATE, QUININE, ERGOTAMINE TARTRATE AND CAFFEINE: AN ANALYSIS OF THEIR RELATION TO THE PAIN EXPERIENCE

Abstract

Pain threshold raising properties of the above mentioned agents were assayed in man by ascertaining the amt. of heat radiation necessary just to produce the sensation of pain in 3 seconds on 3.5 cm.2 of blackened forehead before, and for 10 min. intervals after the adm. of the agent. Acetylsalicylic acid in quantities from 0.03 g. to 1.8 gs. was thus assayed. The saturation quantity or the smallest amt. with which the highest threshold raising effect was attained (approx. 35% above control level) was 0.3 g. Amts. greater than this, to 1.8 gs., did not raise the threshold further, and increased the duration of effect but slightly. The pain threshold raising action of 0.3 g. of acetanilid, acetophenetidin and aminopyrine, respectively, was similar to that of 0.3 g. acetylsalicylic acid. Acetanilid and acetophenetidin induced greater relaxation, lethargy and difficulties in mentation than did acetylsalicylic acid in comparable amts. Ethyl alc. in amts. of 30 cc. and 60 cc. had a maximum threshold raising action of 40%, with a longer duration of effect for the larger amt. It induced feelings of contentment, relaxation and freedom from anxiety. Pain threshold raising action as well as other observable effects of acetylsalicylic acid, acetanilid, acetophenetidin and ethyl alcohol was but slightly reduced by a uniform pain stimulus introduced just before or during the 1st 60 mins. after adm. of the agents. Thus, antagonism between pain and threshold raising action observed with the opiates is less evident or absent with the above mentioned agents. Alc. accentuates the ability to dissociate pain perception from the pattern of reaction to pain. One cc. of trichlorethylene, inhaled, had a swift threshold raising action of approx. 40% above the control level. A half g. of the Na salt of n-methylcyclohexenylmethyl barbituric acid ("Evipal" brand) had a maximum action of 20%, although profound relaxation, lethargy and defects in mentation were induced. Caffeine sodiobenzoate, ergotamine tartrate and quinine sulphate had no pain threshold raising properties. Various combinations of acetylsalicylic acid, codeine, acetanilid, acetophenetidin, the barbiturates and caffeine had threshold raising effects no greater than that of the most effective ingredient, although psychological effects seemed to summate. A combination is therapeuti-cally valid if it aims to attain useful psychological effects coupled with pain threshold raising action, but it is not valid to assume that pain threshold raising properties of the different ingredients will summate.