Hyaluronic Acid Profhilo® Alleviates Skin Inflammation and Spinal Neuroimmune Alterations in a Mouse Model of Atopic Dermatitis

<i>Background and Objectives</i>: Hyaluronic acid (HA) is extensively used in dermo-aesthetic medicine for its hydrating and tissue-repairing properties. Beyond cosmetic use, HA has shown therapeutic effects in inflammatory skin diseases such as seborrheic, radiation-induced, and atopic dermatitis (AD). However, HA-based aesthetic formulations such as Profhilo^®, a hybrid complex of high- and low-molecular weight HA, have not been tested in immunologically driven models of AD. This study aimed to investigate the therapeutic effects of intradermal Profhilo^® injections in a recently developed ovalbumin (OVA)-induced murine model of AD. Specific objectives included assessing changes in skin inflammation, pain sensitivity, and spinal cord pathology. <i>Materials and Methods</i>: Twenty-eight adult female ICR-CD1 mice were sensitized and exposed to OVA via intraperitoneal, subcutaneous, and topical routes over 49 days to induce AD-like lesions. Control animals received saline. On day 50, mice were subdivided into four groups receiving intradermal injections of Profhilo^® or saline. Skin inflammation was evaluated using the SCORAD index on days 49 and 57, and nociceptive responses were measured using the plantar thermal hyperalgesia test. On day 57, dorsal skin and thoracic spinal cord samples were collected for histological and immunohistochemical analysis, including assessments of epidermal and dermal thickness, mast cell density, collagen content, CGRP immunoreactivity, and microglial activation. <i>Results:</i> OVA-treated mice developed significant skin inflammation (<i>p</i> < 0.0001) and thermal hyperalgesia. Intradermal HA injection significantly reduced SCORAD scores (<i>p</i> < 0.01) and mast cell density (<i>p</i> < 0.05) while increasing dermal thickness (<i>p</i> < 0.05). In the spinal cord, HA treatment reduced CGRP immunoreactivity and microglial activation (<i>p</i> < 0.01 and <i>p</i> < 0.05, respectively), especially in OVA-treated animals. <i>Conclusions:</i> Intradermal Profhilo^® alleviated both cutaneous inflammation and neurogenic pain in an OVA-induced AD model. These findings suggest that HA not only improves local skin pathology but also modulates central neuroimmune responses, supporting its therapeutic potential for inflammatory skin conditions involving peripheral and central sensitization.