Central Effect of Histamine on Formalin - Induced Pain in Rabbits : Role of Opioid System

Objective: To investigate the effect of intracerebroventricular injection of histamine on pain induced by subcutaneous iniection of formalin in the left ear of rabbit and the effect of the amine on morphine analgesia and naloxone hyperalgesia. Design: Experimental study. Animals: Sixty - six male New Zealand white rabbits weighing 2.640.16Kg. Procedure: Intracerebroventricular injections of the following drug solutions were done: normal saline (control), histamine (22.5,451tg and 90pg ), morphine and naloxone (50pg and 100 pg), histamine (45pg) before morphine (50pg) and histamine (90pg) after naloxone (100pg).For induction of Pain Subcutaneous injections normal saline (control) and formalin (100, 57o) were done Responses including the durations of head and ear movements and ear scratching were recorded in the five min intervals for th. Statistical analysis: One-way ANOVA, repeated measures ANOVA and Duncan's test. Results: While normal saline produced any significant response, formalin injection induced a short-lasting (10 min) pain response. Histamine at the dose of 22.5trrg had no effect on head and ear movements and scratching durations, but at the doses of 45 and 90pg suppressed the pain response. Morphine (50 and l00pg) and Naloxone (50 and l00pg) induced antinociception and hyperalgesia, respectively, while I.c.v. injection of histamine (45ttg) before morphine (50pg) increased the antinociceptive effect of morphine Moreover, at the dose of (90pg) after naloxone (l00ptg) attenuated the naloxone induced hyperalgesia. Clinicat implication: Activation of brain histamine produces antinociception. Morphine induces analgesia and naloxone produces hyperalgesia. Histamine potentiates the morphine analgesia and attenuates naloxone hyperalgesia' The antinociceptive effect of histamine may be independent of opioid system.