Morphine doesn´t Release Histamine

The Morphine (MPH) is an enigmatic compound, well-known from ancestral times. It has a wide variety of uses like medication. MPH is used as analgesic, coadjutant of the anesthesia, to relieve cough, to treat diarrhea, and as general anesthetic. It is used in small dose to palliate the constant pain and in moderate dose to big for the pain of traumatic or visceral origin.  In this manuscript the property of the MPH is described of not liberating histamine as a result of its administration via intrathecal (i.t.) in a preclinical model.

            It is known that i.v. injections of morphine can increase plasma levels of histamine and this has been thought to cause skin flushing and itching in facial, neck and anterior thoracic areas in patients. Interestingly, i.t. injections of MPH in nonanesthetized mice cause a dramatic behavioral syndrome showing mainly as intense scratching and biting of fore limbs and hind limbs, which may be due to severe pruritus.

            We have investigated whether this response was diminished or abolished with antihistamines. To determine if the antihistamines, diphenhydramine (DY) or pyrilamine (PY), antagonize the dramatic behavioral syndrome due to high dose of MPH i.t. in nonanesthetized mice.

            To this end, 96 BALB/c mice were separated randomly into 8 groups of 12 animals each. Two control groups were pretreated. 30 minutes before morphine i.t. with isotonic saline by s.c. injection. Three other groups received DY s.c. at dose levels of 6.3, 12.5, and 25 mg/kg respectively. The remaining three groups received PY s.c. of 12.5, 25, and 50 mg/kg. After 30 minutes each mouse was injected with 50 micrograms/mouse of MPH i.t.

            All animals pretreated with saline, DY or PY at the identified dose levels which then received MPH i.t. displayed the behavioral scratching, biting syndrome which was unaffected by the antihistamine.

            These experimental results suggest that histamine release may not follow applications of MPH i.t. or that other histamine receptors may be involved in the response, or alternatively other substances, such as serotonin, may be liberated. It is noteworthy that initial studies involving applications of histamine i.t. to mice did not produce any scratching behavior, which may imply that histamine itself may not be involved in this interesting phenomenon.

Footnote: this work was presented in the IX World Conference on Clinical Pharmacology  and Therapeutics in the day July 27 at August 1° of 2008 in Québec City, Canada.

A.    . Luna and U. Estrada   


Corrigendum: Morphine is not a general anesthetic.