Role of voltage-gated sodium channel 1.5 in TrkB-positive neurons in the development of streptozotocin-induced diabetic neuropathic pain.

• Grant number: 25/15219-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Thiago Mattar Cunha
• Grantee: Luiz Gustavo Kanada
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Pain is a fundamental sensory and emotional experience essential for survival, acting as a defense mechanism by signaling injuries or harmful changes in the body. However, in neuropathic pain, originating from lesions or dysfunctions in the somatosensory system, this protective role is lost, leading to a chronic and debilitating condition. A common example is diabetic neuropathy, which affects millions of people and manifests as pain, burning, and tingling sensations. It is known that hyperglycemia contributes to the degeneration of peripheral nerve fibers, and given the limited efficacy of current treatments, there is an urgent need for new therapeutic strategies. In this scenario, voltage-gated sodium channels have been widely investigated for their role in neuronal excitability. Although subtypes such as Nav1.7 have shown potential, clinical results are still unsatisfactory. Our group proposes to investigate the Nav1.5 channel, less studied in the context of pain, but with possible involvement in neuronal excitability and differentiation. Using a murine model of streptozotocin-induced diabetic neuropathy, we observed increased expression of the Scn5a gene, encoding Nav1.5, in the dorsal root ganglia of the spinal cord. In addition, our transcriptomic approaches identified that TrkB-positive neurons carry increased expression of Nav1.5 in mice and humans. Therefore, our goal is to characterize the role of Nav1.5 in the pathophysiology of diabetic neuropathic pain. Validation of this hypothesis may reveal a new promising therapeutic target for the treatment of neuropathic pain.