The role of histamine H1, H2 and H3 receptors of ventral posteromedial nucleus of thalamus in modulation of trigeminal pain

Histamine receptors are involved in supraspinal modulation of pain. In the present study, we investigated the effects of microinjection of histamine H1, H2 and H3 receptor antagonists and agonists into the ventral posteromedial (VPM) nucleus of the thalamus on two models of trigeminal pain. Right and left sides of VPM were implanted with two guide cannulas. Corneal pain was induced by local corneal surface application of hypertonic saline and the number of eye wipes was recorded. The duration of face rubbing, as an orofacial pain measure, was recorded after subcutaneous (s.c.) injection of capsaicin into the vibrissa pad. 2-pyridylethylamine (2-PEA, a histamine H1 receptor agonist, 4 µg/site) and dimaprit (a histamine H2 receptor agonist, 1 and 4 µg/site) suppressed corneal and orofacial pains. Mepyramine (a histamine H1 receptor antagonist) and ranitidine (a histamine H2 receptor antagonist) at the similar doses of 0.5, 2 and 8 µg/site alone had no effects on trigeminal pain. Prior microinjection of mepyramine and ranitidine at a similar dose of 8 µg/site inhibited the antinociceptive effects of 2-PEA (4 µg/site) and dimaprit (4 µg/site), respectively. Immepip (a histamine H3 receptor agonist, 1 and 4 µg/site) increased, and thioperamide (a histamine H3 receptor antagonist, 2 and 8 µg/site) attenuated nociceptive responses. Prior microinjection of thioperamide (8 µg/site) prevented immepip (4 µg/site)-induced nociception. These chemicals did not change locomotor behavior. It is concluded that post-synaptic histamine H2, and to a lesser extent H1, receptors and pre-synaptic histamine H3 receptor may be involved in VPM modulation of trigeminal pain.