Figure 6.

HMWH attenuates mechanical hyperalgesia induced by pronociceptive second messengers. The direct activators of intracellular proalgesic signaling pathways, 8-bromo cAMP (potent PKA activator) or ψεRACK (PKCε activator), both 1 μg, were injected intradermally on the dorsum of the hindpaw; 30 min later, vehicle (white bars) or HMWH (1 μg, black bars) was injected at the same site, and the mechanical nociceptive threshold was evaluated an additional 30 min later. Significant attenuation of hyperalgesia induced by both second messengers was observed in the groups treated with HMWH (8-bromo cAMP groups: t₍₁₀₎ = 8.187, ****p < 0.0001; ψεRACK groups: t₍₁₀₎ = 5.050, ***p = 0.0002, when the vehicle and HMWH groups are compared, unpaired Student's t test), indicating that HMWH induces antihyperalgesia by triggering a signaling pathway that decreases nociceptor sensitization. n = 6 paws per group.