US EPA

1512905 

Journal Article 

Enhanced morphine-induced antinociception in histamine H3 receptor gene knockout mice 

Mobarakeh, JI; Takahashi, K; Yanai, K 

2009 

1 

Neuropharmacology
ISSN: 0028-3908
EISSN: 1873-7064 

57 

4 

409-414 

English 

19589346 

10.1016/j.neuropharm.2009.06.036 

WOS:000270020100009 

http://://WOS:000270020100009
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Previous studies have implicated a potential role for histamine H3 receptor in pain processing. There have been conflicting data, however, on the roles of H3 receptors in pain perception, and little information is available about the role of spinal histamine H3 receptors in morphine-induced antinociception. In the present study we examined the role of histamine H3 receptor in morphine-induced antinociception using histamine H3 receptor knockout mice and a histamine H3 receptor antagonist. Anitinociception was evaluated by assays for four nociceptive stimuli: hot-plate, tail-flick, paw-withdrawal, and formalin tests. Antinociception induced by morphine (0.125 nmol/5 microl, i.t.) was significantly augmented in histamine H3 receptor knockout (-/-) mice compared to the wild-type (+/+) mice in all four assays of pain. Furthermore, the effect of intrathecally administered morphine with thioperamide, a histamine H3 antagonist, was examined in C57BL/6J mice. A low dose of i.t. administered thioperamide (0.125 nmol/5 microl) alone had no significant effect on the nociceptive response. In contrast, the combination of morphine (0.125 nmol/5 microl, i.t.) with the same dose of thioperamide resulted in a significant reduction in the pain-related behaviors in all four nociceptive tests. These results suggest that histamine exerts inhibitory effects on morphine-induced antinociception through H3 receptors at the spinal level. 

Histamine H3 receptor; Gene knockout mice; Thioperamide; Morphine; Pain; Central nervous system