Histopathological evaluation of cocaine‐induced skin lesions in the rat

Abstract

A series of experiments was performed to characterize the nature of local tissue reactions to cocaine. The time‐course of tissue injury was assessed over a 21‐day period by gross and microscopic examination of the skin of rats administered 0.1–2.0% cocaine hydrochloride by i.e. or s.c. injection. Pronounced blanching, progressively severe hemorrhage, delayed extravasation of Evans blue dye, and eventual scar formation were seen grossly at injection sites. Marked engorgement of blood vessels, small hemorrhagic foci, and hyalinization of scattered muscle bundles of the pannieulus carnosus were apparent microscopically at 15 min post‐injection. Subsequent changes during (he next 3 h included progressively severe hemorrhage and loss of muscle bundles, degeneration of hair follicles and necrosis of the vascular endothelium and epidermis. Healing of cocaine‐induced lesions, as monitored for 21 days, was relatively rapid and complete. A hyperplastic epidermis covered formerly ulcerated areas by 6 days. Destroyed cellular structures in the derm is were replaced by collagen. Since cocaine's local tissue toxicity has been ascribed to vasoconstriction, the toxic potential of cocaine was contrasted with that of a potent vasoconstrictor, epinephrine (EPI). Although 0.1% EPI produced greater vasoconstriction than did cocaine, s.c. injection of EPI did not result in skin damage. The slight acidity of cocaine hydrochloride solutions appeared to be of little consequence, since s.c. injection of pH 5 and 6 saline had little effect on tissues. Our results suggest that cocaine is directly cytotoxic, though ischemia resulting from vascular injury and vasoconstriction may contribute to the local tissue injury caused by the drug.

Rhesus Macaque Model of Chronic Opiate Dependence and Neuro-AIDS: Longitudinal Assessment of Auditory Brainstem Responses and Visual Evoked Potentials

“…It is noteworthy that cutaneous complications associated with injection drug use are well documented and include cutaneous infections (Beaufoy 1993; Binswanger et al, 2000; Spijkerman et al, 1996b), necrotizing fasciitis (Callahan et al, 1998; Chen et al, 2001) and necrotizing ulcers (Bruckner et al, 1982; Scott et al, 1997). The possibility of local immune suppression at the site of morphine injections can be raised although it would seem that the VM group monkeys would also be affected.…”

The Role of Vascular Mechanisms in the Development of Acute Equine Laminitis

“…Cellular swelling, hydropic degeneration, and pyknotic nuclei are changes consistent with ischemic and/or toxic damage to cells but do not reflect a specific eti~logy.~' Leukocytic infiltrates in the acutely affected horse with laminitis are consistent with both postischemic and toxic mechanisms. 39,43,44 Epithelial hyperplasia is evident within 8 hours and is not uniformly distrib~ted.~'-~~ Hyperplasia is most notable in regions nearest the base of the primary dermal lamina and reflects an apparent splitting of basal cells into two distinct populations (a stem cell and committed cell pool) and an increase in the number of the spinous cell layers. Decreased onychogenic substance associated with decreased synthesis, swelling, and cessation of the bundling of keratin fibers have been reported as early as 24 h o~r s .~~,~~ H yperkeratinization is notable after 10 to 20 days.…”

Behavioral responses during the initial exposures to a low dose of cocaine in late preweanling and adult rats

“…Alerted by published accounts of skin lesions caused by s.c. injections in laboratory rats [11,63,73], we checked the injection areas daily in animals that received repeated s.c. drug administration; no skin lesions were found.…”