Investigation of trigeminal neuroinflammatory mechanisms modulated by non-antibiotic tetracycline derivatives in trigeminal neuralgia

• Grant number: 25/13597-2
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Dentistry - Dental Clinics
• Principal Investigator: Glauce Crivelaro Do Nascimento
• Grantee: Glauce Crivelaro Do Nascimento
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• City of the host institution: Ribeirão Preto
• Associated research grant: 23/14005-6 - Investigation of the analgesic effects of new non-antibiotic tetracycline derivatives on mechanical allodynia and thermal hyperalgesia in a preclinical model of trigeminal neuralgia, AP.R

Abstract

Trigeminal neuralgia is one of the most disabling forms of facial pain, characterized by sudden episodes of intense pain triggered by innocuous stimuli in areas innervated by the trigeminal nerve. Its pathophysiology involves central and peripheral structural changes, and many patients are refractory to treatment with anticonvulsants, in addition to presenting significant side effects. Neuroinflammation appears to be a key factor in the genesis of pain in neuralgia, with increased arachidonic acid, which impairs glutamate uptake and favors neuropathic pain. Pro-inflammatory cytokines such as TNF-¿ and IL-1¿ also contribute to the dysfunction of astroglial glutamate transporters, GLT1 and GLAST3. Furthermore, the imbalance between pro- and anti-inflammatory cytokines is one of the central mechanisms in the development and maintenance of trigeminal neuropathic pain. Tetracyclines have demonstrated analgesic, anti-inflammatory and neuroprotective effects independent of antibacterial action. However, prolonged use of these drugs may affect the microbiota and favor antimicrobial resistance. As an alternative, compounds derived from tetracyclines without antibiotic activity have been developed. This project proposes to evaluate the effects of two chemically modified tetracyclines, without antimicrobial action, in an animal model of trigeminal neuralgia, focusing on the modulation of neuroinflammation in the trigeminal system. (AU)