Different groups of rats received an intradermal injection of vehicle (control, blank bars), the PKA inhibitor H-89 (1 μg, light gray bars), the non-selective PKC inhibitor BIMM (1 μg, darker gray bars) or the Src inhibitor SU6656 (1 μg, black bars) on the dorsum of the hind paw. 10 minutes later, LMWH (1 μg, panel A) or the CD44 agonist A6 (1 μg, panel B) was injected at the same site. Mechanical nociceptive thresholds were evaluated before and 30 min after LMWH/A6. We observed significant hyperalgesia in the control and the BIMM-treated groups (both panels). However, in the groups pretreated with H-89 or SU6656 there was significant attenuation of mechanical hyperalgesia (**** p < 0.0001; *** p = 0.005, when the groups treated with H-89 or SU6656 are compared to the control groups), indicating a role of PKA and Src in the hyperalgesia induced by LMWH and A6. (One-way ANOVA followed by Bonferroni's post hoc test; n = 6 paws per group)