Combined Systemic and Cutaneous Ovalbumin–Aluminum Sensitization Triggers Thermal Hyperalgesia, Spinal Gliosis, and Nociceptive Nerve Fibers Sprouting in Mice

Background/Objectives: This study investigates whether systemic ovalbumin–aluminum sensitization followed by cutaneous challenge induces thermal hyperalgesia and spinal cord gliosis in mice. Methods: Adult female ICR-CD1 mice received ovalbumin–aluminum salt solution intraperitoneally on days 0, 7 and 14, and subcutaneously with daily skin application via brush during days 15–21, 28–35 and 42–49. Control animals received saline. Plantar thermal hyperalgesia was assessed on days 21, 35 and 49. On day 49, tissues (dorsal skin, spinal cord, footpads) were harvested after perfusion and processed histologically to detect mast cells, astrocytes, microglia, afferent fibers and intraepidermal nerve profiles. Results: Ovalbumin-treated mice displayed thermal hyperalgesia, increased astrogliosis, and reactive microglia in the spinal cord, and expanded CGRP- and IB4-immunoreactive fiber areas. In footpads, CGRP-positive intraepidermal nerve profile density was elevated, and dorsal skin showed increased mast cell density compared to controls. Conclusions: Combined systemic and cutaneous ovalbumin–aluminum sensitization induces skin inflammation, spinal gliosis, and nociceptive fiber sprouting in both central and peripheral sites, which likely contribute to the observed thermal hyperalgesia.