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

1
Special Laboratory of Pain and Signalling, Butantan Institute, São Paulo 05503-900, Brazil
2
Laboratory of Immunochemistry, Butantan Institute, São Paulo 05503-900, Brazil
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(12), 679; https://doi.org/10.3390/toxins11120679
Received: 5 September 2019 / Revised: 13 November 2019 / Accepted: 18 November 2019 / Published: 20 November 2019
(This article belongs to the Section Animal Venoms)
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. View Full-Text
Keywords: neuropathic pain 1; crotoxin 2; SBA-15 nanostructured silica 3; partial sciatic nerve ligation 4; analgesia 5; hypernociception 6 neuropathic pain 1; crotoxin 2; SBA-15 nanostructured silica 3; partial sciatic nerve ligation 4; analgesia 5; hypernociception 6
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Sant’Anna, M.B.; Lopes, F.S.R.; Kimura, L.F.; Giardini, A.C.; Sant’Anna, O.A.; Picolo, G. Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice. Toxins 2019, 11, 679.

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