Search Results (5)

Background/Objectives: Diabetic small fiber neuropathy and related sensory and epidermal problems affect up to 70% of all patients with diabetes. Long-term hyperglycemia disrupts cytoskeletal organization and axonal transport; however, molecular changes within human diabetic epidermis remain understudied. Diaph1 and its cytoskeletal ligands, including β-Actin and Profilin, are key regulators of cytoskeletal dynamics and may be associated with diabetes-related alterations in skin structure and innervation. Methods: Sixteen patients with type 2 diabetes, aged 43.3 ± 9.6 years (disease duration 18.9 ± 8.7 years), and twelve non-diabetic controls, aged 43.9 ± 8.9 years, were enrolled in the study. All participants provided informed consent. Skin punch biopsies were obtained under local anesthesia and processed for staining of PGP 9.5, Diaph1, β-Actin, and Profilin. Quantitative image analysis was performed to assess stained area fraction, signal intensity, and intraepidermal nerve fiber density. Statistical comparisons and Spearman’s rank correlation analyses were used to evaluate group differences and associations between staining parameters. Results: Diabetic skin samples exhibited a significant reduction in PGP 9.5-positive intraepidermal nerve fibers, indicating reduced cutaneous innervation. In contrast, Diaph1 and Profilin showed broader and more diffuse epidermal staining, while β-Actin displayed altered staining patterns and intensity. Significant correlations between Diaph1- and β-Actin-related staining measures indicated an association consistent with altered cytoskeletal organization under chronic hyperglycemic conditions. Conclusions: Long-standing type 2 diabetes was associated with reduced PGP 9.5-positive intraepidermal nerve fibers, together with altered epidermal staining patterns of Diaph1, Profilin and β-Actin. These findings indicate coexisting cutaneous denervation and cytoskeletal alterations in diabetic skin. Full article

The article introduces neurotrophic keratopathy (NK), a condition resulting from corneal denervation due to various causes of trigeminal nerve dysfunctions. Surgical techniques for corneal neurotization (CN) have evolved, aiming to restore corneal sensitivity. Initially proposed in 1972, modern approaches offer less invasive options. CN can be performed through a direct approach (DCN) directly suturing a sensitive nerve to the affected cornea or indirectly (ICN) through a nerve auto/allograft. Surgical success relies on meticulous donor nerve selection and preparation, often involving multidisciplinary teams. A PubMed research and review of the relevant literature was conducted regarding the surgical approach, emphasizing surgical techniques and the choice of the donor nerve. The latter considers factors like sensory integrity and proximity to the cornea. The most used are the contralateral or ipsilateral supratrochlear (STN), and the supraorbital (SON) and great auricular (GAN) nerves. Regarding the choice of grafts, the most used in the literature are the sural (SN), the lateral antebrachial cutaneous nerve (LABCN), and the GAN nerves. Another promising option is represented by allografts (acellularized nerves from cadavers). The significance of sensory recovery and factors influencing surgical outcomes, including nerve caliber matching and axonal regeneration, are discussed. Future directions emphasize less invasive techniques and the potential of acellular nerve allografts. In conclusion, CN represents a promising avenue in the treatment of NK, offering tailored approaches based on patient history and surgical expertise, with new emerging techniques warranting further exploration through basic science refinements and clinical trials. Full article

Distal diabetic sensorimotor polyneuropathy (DDSP) is the most prevalent form of diabetic neuropathy, and some of the patients develop gradual pain. Specialized sensory structures present in the skin encode different modalities of somatosensitivity such as temperature, touch, and pain. The cutaneous sensory structures responsible for the qualities of mechanosensitivity (fine touch, vibration) are collectively known as cutaneous mechanoreceptors (Meissner corpuscles, Pacinian corpuscles, and Merkel cell–axonal complexes), which results are altered during diabetes. Here, we used immunohistochemistry to analyze the density, localization within the dermis, arrangement of corpuscular components (axons and Schwann-like cells), and expression of putative mechanoproteins (PIEZO2, ASIC2, and TRPV4) in cutaneous mechanoreceptors of subjects suffering clinically diagnosed non-painful and painful distal diabetic sensorimotor polyneuropathy. The number of Meissner corpuscles, Pacinian corpuscles, and Merkel cells was found to be severely decreased in the non-painful presentation of the disease, and almost disappeared in the painful presentation. Furthermore, there was a marked reduction in the expression of axonal and Schwann-like cell markers (with are characteristics of corpuscular denervation) as well as of all investigated mechanoproteins in the non-painful distal diabetic sensorimotor polyneuropathy, and these were absent in the painful form. Taken together, these alterations might explain, at least partly, the impairment of mechanosensitivity system associated with distal diabetic sensorimotor polyneuropathy. Furthermore, our results support that an increasing severity of DDSP may increase the risk of developing painful neuropathic symptoms. However, why the absence of cutaneous mechanoreceptors is associated with pain remains to be elucidated. Full article

Four patients underwent targeted sensory reinnervation (TSR), a surgical technique in which a defined skin area is first selectively denervated and then surgically reinnervated by another sensory nerve. In our case, either the area of the lateral femoral cutaneous nerve or the saphenous nerve was reinnervated by the sural nerve. Patients were then fitted with a special prosthetic device capable of transferring the sense of pressure from the sole of the prosthesis to the newly wired skin area. Pain reduction after TSR was highly significant in all patients. In three patients, permanent pain medication could even be discontinued, in one patient the pain medication has been significantly reduced. Two of the four patients were completely pain-free after the surgical intervention. Surgical rewiring of existing sensory nerves by TSR can provide the brain with new afferent signals seeming to originate from the missing limb. These signals help to reduce phantom limb pain and to restore a more normal body image. In combination with special prosthetic devices, the amputee can be provided with sensory feedback from the prosthesis, thus improving gait and balance. Full article

Wallerian degeneration or nerve demyelination, arising from spinal nerve compression, is thought to bring on chronic neuropathic pain. The widely distributed metabotropic glutamate receptor subtype 5 (mGluR5) is involved in modulating nociceptive transmission. The purpose of this study was to investigate the potential effects of mGluR5 on peripheral hypersensitivities after chronic constriction injury (CCI). Sprague-Dawley rats were operated on with four loose ligatures around the sciatic nerve to induce thermal hyperalgesia and mechanical allodynia. Primary afferents in dermis after CCI exhibited progressive decreases, defined as partial cutaneous denervation; importantly, mGluR5 expressions in primary afferents were statistically increased. CCI-induced neuropathic pain behaviors through the intraplantar injections of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, were dose-dependently attenuated. Furthermore, the most increased mGluR5 expressions in primary afferents surrounded by reactive Schwann cells were observed at the distal CCI stumps of sciatic nerves. In conclusion, these results suggest that nerve demyelination results in the increases of mGluR5 expression in injured primary afferents after CCI; and further suggest that mGluR5 represents a main therapeutic target in developing pharmacological strategies to prevent peripheral hypersensitivities. Full article