Behavioral and peripheral nerve fiber effects of a topical nanoemulgel containing 5% lidocaine + 0.075% capsaicin in a diabetic neuropathy model.
Diabetic Neuropathy; Diabetic Polyneuropathy; Nerve Regeneration; Capsaicin; Lidocaine
The most common manifestation of Diabetic Neuropathy (DN), Distal Symmetric Polyneuropathy (DSP), is marked by the gradual and progressive loss of protective sensation, which increases the risk of diabetic foot complications such as ulcers and amputations. Initially, this condition manifests as alterations in the perception of thermal and painful stimuli in the lower extremities. Diagnosis is frequently associated with increased thermal sensitivity thresholds in cold and heat tests, along with a reduction in the density of intraepidermal nerve fibers (A-delta and C) on histological examination. This study aims to investigate whether the topical application of a capsaicin and lidocaine nanoemulgel can restore protective sensation and promote nerve regeneration in the paws of rats with type I diabetes. Male Wistar rats were used. Diabetes was induced by administering streptozotocin at a dose of 65 mg/kg, in a single intraperitoneal dose. The animals were initially divided into two groups: healthy animals (without diabetes) and diabetic animals. Each group was subsequently subdivided into three subgroups: Control/Excipients: treated with vehicle; Control/Commercial formulation: treated with 0.075% commercial capsaicin; Experimental group/FLC nanoemulgel: treated with 5% lidocaine + 0.075% capsaicin nanoemulgel. Treatments were administered topically to the plantar region of the paws, three times a day, for 15 days. Protective sensitivity was quantitatively assessed using the Hot Plate test at 47 °C. Analysis of nerve regeneration, using skin biopsy with PGP 9.5 immunostaining, is ongoing. Behavioral findings in the hot plate test, in healthy animals, demonstrated that treatment with FLC nanoemulgel did not alter thermal sensitivity in intact skin when compared to the control group (p = 0.425). In diabetic animals, in the intragroup analysis (pre-treatment vs. post-treatment), none of the treatments were able to reverse hypoalgesia. However, the commercial formulation worsened the condition (p = 0.0313), while the FLC nanoemulgel (p = 0.3125) and the control/excipients group (p = 1.000) did not worsen hyposensitivity. The intergroup analysis confirmed a significant difference between the FLC nanoemulgel and the commercial cream (positive control) (p = 0.0070). No significant difference was observed between the FLC nanoemulgel and the control/excipients group. The partial results suggest that, although the FLC nanoemulgel was not able to restore diabetic hypoalgesia, it presented a superior safety profile to the commercial treatment, since it did not worsen thermal hyposensitivity. The definitive conclusion regarding the therapeutic efficacy of FLC nanoemulgel will depend on the results of the intraepidermal nerve fiber density (PGP 9.5) analysis, which will complement the findings.