Fig. 2.

Biphasic modulation of acute nociceptive responses by thioperamide (Thio) and histamine (HA). Data from published studies show dose-response curves for Thio and HA in mice (top) and rats (bottom) on the hot-plate test. Antinociceptive scores (ordinate, maximal possible effect; see Li et al., 1996) range from 0 to 100%. Thio was administered by systemic (intraperitoneal; top) or intracerebral injections into the PAG (bottom). The figure shows that: 1) the biphasic actions of systemically injected Thio can be replicated by microinjections of the same drug into the PAG, and 2) intracerebral HA injections in the PAG can closely mimic the effects of Thio, consistent with the known HA-releasing properties of this H₃ inverse agonist. Data are plotted: a, 15 min after Thio (Malmberg-Aiello et al., 1994); b, 40 min after Thio (Farzin et al., 2002); c, 10 min after intra-PAG Thio (Li et al., 1996); d, 5 min after intra-PAG HA (Thoburn et al., 1994).