Fig. 1.

Effects of P2Y₁₂R antagonists in rat models of inflammatory, neuropathic and acute pain. A, B. Mechanical hyperalgesia (A) and edema (B) before (PRE) after (CFA) intraplantar CFA injection in rats. CFA (100 μl, 50% in saline) was injected intradermally into the plantar surface of the right hind paw. 48 h after treatment with CFA, the extent of edema and mechanical sensitivity were measured on both hind paws. Paw withdrawal threshold values are presented in grams, whereas paw volume values are expressed in ml (mean ± S.E.M.). Injected (CFA), but not control paws demonstrated a significant, 49% decrease of pain threshold and 47% increase in paw volume. *** denotes statistical significance of P < 0.001, Student t test. C, D. Effects of clopidogrel (C) and PSB-0739 i.t. (D) on CFA mediated inflammatory pain behavior 48 h after injection in rats. The graphs show the PWT values in g corresponding to doses indicated on the abscissa. Symbols indicate significant differences from the pre-CFA treatment (**P < 0.01) and post-CFA treatment PWT values (^##P < 0.01, ^###P < 0.001), respectively. One-way ANOVA followed by Neuman–Keuls post-hoc test, n = 6–12/group. E, F. Effects of clopidogrel (E) and PSB-0739 i.t. (F) on neuropathic pain behavior in rats. PWT values were assessed on operated (white triangles) and contralateral hind paws (black triangles) expressed in g. Asterisks indicate significant differences from the postoperative values of saline (SAL) or vehicle (VEH) treated animals (*P < 0.05, **P < 0.01, ***P < 0.001). One-way ANOVA followed by Neuman–Keuls post-hoc test, n = 6–12/group. G, H. Effects of clopidogrel (G) and PSB-0739 i.t. (H) on acute thermal nociception in rats. Y axis values show the change in nocifensive threshold (∆PWT, °C). Animals were treated with P2Y₁₂ receptor antagonists in doses indicated on the abscissa. Asterisks indicate significant analgesic effect, compared to the pre-treatment values, *P < 0.05, **P < 0.01, paired t-test.