Aim:
The study aimed to determine the peculiarities of the micro- and ultrastructural organization of the skin under conditions of a four-week administration of an opioid to experimental animals.

Material and methods:
The study material included skin samples of white rats with injected vascular beds, histological preparations, and ultrathin skin sections. Research methods involved injection techniques, histological analysis, electron microscopy, morphometric measurements, and statistical analysis.

Results:
The results of the study revealed that after four weeks of nalbuphine administration to experimental animals, blood stasis was observed in the lumen of capillaries and venules, along with perivascular edema and perivascular infiltrates consisting of neutrophils, lymphocytes, macrophages, and tissue basophils. The electron density of the nuclei and cytoplasm of granular layer keratinocytes was reduced, keratinocytes in the stratum spinosum acquired a rounded shape, with some nuclei appearing shrunken and hyperchromatic, and their cytoplasm exhibiting vacuolization. In the reticular layer, thickened bundles of collagen fibers were observed, with localized swelling and fragmentation of the collagen fibers. Excessive formation of scales was noticed in the stratum corneum. The papillary layer of the dermis contained numerous mast cells and lymphocytes near blood vessels.

Conclusions:
Four weeks of nalbuphine administration induces irreversible pathological processes in all skin components.