Analgesic effects of human placental hydrolysate on capsaicin-induced hyperalgesia in rats.

To explore the analgesic potential of HPH, we examined whether HPH could reduce primary and secondary hyperalgesia in a rat model of capsaicin-induced pain and whether co-administration with dexamethasone could provide enhanced analgesia with fewer side effects. HPH was administered in capsaicin-induced pain model. Primary and secondary hyperalgesia were assessed using von Frey filaments. Voltage-sensitive dye imaging (VSDI) was conducted in spinal cord slices to examine neuronal excitability. Immunohistochemistry was performed to evaluate c-Fos and phosphorylated PKCε (p-PKCε) expression. Body weight was monitored as an indicator of corticosteroid-associated side effects in rats treated with dexamethasone alone or in combination with HPH. HPH dose-dependently attenuated capsaicin-induced both primary and secondary hyperalgesia, suppressed spinal dorsal horn hyperactivity, and reduced expression of c-Fos and p-PKCε. Combination of HPH with low-dose dexamethasone produced analgesia comparable to high-dose dexamethasone while reducing corticosteroid-related weight loss, as reflected by body weight loss. HPH effectively alleviated capsaicin-induced neurogenic inflammatory pain and enhanced the therapeutic profile of dexamethasone. Co-treatment with low-dose dexamethasone may provide synergistic analgesic benefits while minimizing side effect, supporting HPH as a promising adjunctive therapy for corticosteroid-based pain management.