Pain researchers devised a method for assessing human pain. A blister was induced to the same part of the hand of each subject, and the blister base was used as the testing ground for certain drugs. When serotonin was applied to a blister base, there was a 19 s delay between the time of 5-HT administration and the perception of pain as reported by human volunteers. The figure below is a graphic representation of the pain caused, with pain on the y-axis. Higher concentrations of 5-HT caused more intense pain. This experiment verified the hypothesis that the pain of a wasp sting may be related to the 5-HT content in wasp venom.
In human volunteers, 5-HT was more potent (score=5000) at causing pain than DMT (less than 25), bufotenin (100), and tryptophan (0), as shown in the table below.
An animal model of pain was developed with rats. Each test chemical was injected into the paw of a rat, and the amount of swelling in the paw was measured, in terms of the thickness of the paw in millimeters. A photo of this procedure is shown below. Chemicals such as 5-HT and histamine injected subcutaneously caused local inflammation, or edema, of the paw.
Injected 5-HT to the rat paw was 200X more potent than histamine at causing edema. The graph below shows that 5-HT is more painful than histamine, causing more edema at lower doses. A mere dose of 1 ug 5-HT per paw caused a swelling reaction.
The swelling caused by 5-HT injection was prevented by pre-treatment of rats with LSD and certain phenothiazine drugs.
Lewis G. P. (Ed.) 5-Hydroxytryptamine. New York, Pergamon Press, 1958.
Doepfner W. and A. Cerletti (1958). Comparison of lysergic acid derivatives and antihistamines as inhibitors of the edema provoked in the rat's paw by serotonin. International archives of allergy and applied immunology 12, 89-97.