The present study was aimed to investigate the effects of microinjection of
histamine,
chlorpheniramine (a
histamine H(1) receptor antagonist),
ranitidine (a
histamine H(2) receptor antagonist) and
thioperamide (a
histamine H(3) receptor antagonist) into the dentate gyrus on the
formalin-induced
pain. A biphasic pattern (first phase: 0-5min and second phase: 15-60min) in nociceptive responses was induced after
subcutaneous injection of
formalin (50μl, 2.5%) into the ventral surface of the right hind paw. Microinjection of
histamine (1 and 2μg) into the dentate gyrus decreased the intensity of nociceptive responses. Intra-dentate gyrus microinjection of
chlorpheniramine and
ranitidine at the same doses of 1 and 4μg had no effects, whereas
thioperamide at a dose of 4μg suppressed both phases of
formalin-induced
pain. Pretreatments with
chlorpheniramine and
ranitidine at the same dose of 4μg prevented
histamine (2μg)-induced antinociception, while
thioperamide (4μg) increased
histamine (2μg)-induced antinociception. These results indicated that activation of brain neuronal
histamine at the levels of dentate gyrus produced antinociception. The post-synaptic H(1), H(2) receptors and pre-synaptic H(3) receptors of
histamine may be involved in the
histamine-induced antinociception at the level of the dentate gyrus.