A minocycline derivative reduces nerve injury-induced allodynia, LPS-induced prostaglandin E2 microglial production and signaling via toll-like receptors 2 and 4

Download
  1. Get@NRC: A minocycline derivative reduces nerve injury-induced allodynia, LPS-induced prostaglandin E2 microglial production and signaling via toll-like receptors 2 and 4 (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1016/j.neulet.2013.03.014
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titleNeuroscience Letters
ISSN0304-3940
Volume543
Pages157162; # of pages: 6
Subjectcalcium; divalent cation; hydroxy 1,12 pyrazolinominocycline; magnesium ion; minocycline; prostaglandin E2; pyrazoline derivative; toll like receptor 2; toll like receptor 4; unclassified drug; allodynia; animal cell; animal experiment; animal model; animal tissue; antibacterial activity; antiinflammatory activity; article; cell viability; chelation; controlled study; female; genetic transfection; human; in vitro study; kidney cell; microglia; mouse; nerve injury; neuropathic pain; nonhuman; priority journal; sham procedure; single drug dose; treatment duration; treatment outcome; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Dinoprostone; Female; Humans; Hyperalgesia; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Microglia; Minocycline; Neuralgia; Physical Stimulation; Rats; Rats, Wistar; Sciatic Nerve; Signal Transduction; Toll-Like Receptor 2; Toll-Like Receptor 4; Touch
AbstractMany studies have shown that minocycline, an antibacterial tetracycline, suppresses experimental pain. While minocycline's positive effects on pain resolution suggest that clinical use of such drugs may prove beneficial, minocycline's antibiotic actions and divalent cation (Ca2+; Mg2+) chelating effects detract from its potential utility. Thus, we tested the antiallodynic effect induced by a non-antibacterial, non-chelating minocycline derivative in a model of neuropathic pain and performed an initial investigation of its anti-inflammatory effects in vitro. Intraperitoneal minocycline (100mg/kg) and 12S-hydroxy-1,12-pyrazolinominocycline (PMIN; 23.75mg/kg, 47.50mg/kg or 95.00mg/kg) reduce the mechanical allodynia induced by chronic constriction injury of mouse sciatic nerve. PMIN reduces the LPS-induced production of PGE2 by primary microglial cell cultures. Human embryonic kidney cells were transfected to express human toll-like receptors 2 and 4, and the signaling via both receptors stimulated with PAM3CSK4 or LPS (respectively) was affected either by minocycline or PMIN. Importantly, these treatments did not affect the cell viability, as assessed by MTT test. Altogether, these results reinforce the evidence that the anti-inflammatory and experimental pain suppressive effects induced by tetracyclines are neither necessarily linked to antibacterial nor to Ca2+ chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the management of neuropathic pain, as its lack of antibacterial and Ca2+ chelating activities might confer greater safety over conventional tetracyclines. © 2013 Elsevier Ireland Ltd.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Biotechnology Research Institute (BRI-IRB)
Peer reviewedYes
NPARC number21269812
Export citationExport as RIS
Report a correctionReport a correction
Record identifieraf84025d-8c30-4609-9eec-136753e51296
Record created2013-12-13
Record modified2016-05-09
Bookmark and share
  • Share this page with Facebook (Opens in a new window)
  • Share this page with Twitter (Opens in a new window)
  • Share this page with Google+ (Opens in a new window)
  • Share this page with Delicious (Opens in a new window)