Solutions of morphin and its esters, when introduced into the skin, produce local reactions, consisting of the urticarial wheal with an erythematous areola (Sollmann and Pilcher1). The lesions are quite like those formed in susceptible individuals by the local inoculation of foreign proteins, and in probably all individuals by inoculation of histamin or any one of a series of definite chemical substances (Sollmann2).
This local reaction to the morphins raised a number of interesting questions, some of which will be considered in this paper. Perhaps the most important of these concerns the possibility of the modification of the local reaction by habituation. Does the high degree of tolerance to the toxic actions of the morphins that is acquired by addicts extend also to the local reactions? or, stated conversely, does the local reaction vary with changes in the systemic susceptibility, as is the case with desensitization or "habituation" to
PILCHER JD, SOLLMANN T. THE SKIN-REACTION TO MORPHIN. Arch Intern Med (Chic). 1924;33(4):516-524. doi:10.1001/archinte.1924.00110280114012