Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice

Author(s)

Sant'Anna, Morena Brazil ^[1] ; Ribeiro Lopes, Flavia Souza ^[1] ; Kimura, Louise Faggionato ^[1] ; Giardini, Aline Carolina ^[1] ; Sant'Anna, Osvaldo Augusto ^[2] ; Picolo, Gisele ^[1]

Affiliation

^[1] Butantan Inst, Special Lab Pain & Signalling, BR-05503900 Sao Paulo - Brazil

^[2] Butantan Inst, Lab Immunochem, BR-05503900 Sao Paulo - Brazil

• Document type: Journal article
• Source: TOXINS; v. 11, n. 12 DEC 2019.
• Web of Science Citations: 1

Abstract

Neuropathic pain is a disease caused by structural and functional plasticity in central and peripheral sensory pathways that produce alterations in nociceptive processing. Currently, pharmacological treatment for this condition remains a challenge. Crotoxin (CTX), the main neurotoxin of Crotalus durissus terrificus rattlesnake venom, has well described prolonged anti-inflammatory and antinociceptive activities. In spite of its potential benefits, the toxicity of CTX remains a limiting factor for its use. SBA-15 is an inert nanostructured mesoporous silica that, when used as a vehicle, may reduce toxicity and potentiate the activity of different compounds. Based on this, we propose to conjugate crotoxin with SBA-15 (CTX:SBA-15) in order to investigate if when adsorbed to silica, CTX would have its toxicity reduced and its analgesic effect enhanced in neuropathic pain induced by the partial sciatic nerve ligation (PSNL) model. SBA-15 enabled an increase of 35% of CTX dosage. Treatment with CTX:SBA-15 induced a long-lasting reduction of mechanical hypernociception, without modifying the previously known pathways involved in antinociception. Moreover, CTX:SBA-15 reduced IL-6 and increased IL-10 levels in the spinal cord. Surprisingly, the antinociceptive effect of CTX:SBA-15 was also observed after oral administration. These data indicate the potential use of the CTX:SBA-15 complex for neuropathic pain control and corroborates the protective potential of SBA-15. (AU)

• FAPESP's process: 15/01254-1 - Evaluating the effect of crotoxin-nanostructured silica SBA-15 complex in chronic pain: immunomodulatory, antinociceptive and antiinflammatory aspects
• Grantee: Gisele Picolo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/19397-0 - Evaluating the effect of crotoxin conjugated nanostructured silica SBA-15 in chronic pain: immunomodulatory, antinociceptive and antiinflammatory aspects
• Grantee: Morena Brazil Martins Sant'Anna
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/17844-8 - Nanostructured silica as a protective vehicle for vaccines and biomolecules
• Grantee: Osvaldo Augusto Brazil Esteves Sant'Anna
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 08/57898-0 - National Institute of Science and Technology on Toxins
• Grantee: Osvaldo Augusto Brazil Esteves Sant'Anna
• Support Opportunities: Research Projects - Thematic Grants