The effects of pregabalin and the glial attenuator minocycline on the response to intradermal capsaicin in patients with unilateral sciatica

dc.contributor.authorSumracki, N.
dc.contributor.authorHutchinson, M.
dc.contributor.authorGentgall, M.
dc.contributor.authorBriggs, N.
dc.contributor.authorWilliams, D.
dc.contributor.authorRolan, P.
dc.contributor.editorIkeda, K.
dc.date.issued2012
dc.description.abstractBACKGROUND: Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes. AIM: This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg. METHODS/RESULTS: Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 mg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce precapsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (-38% in affected leg, 95% CI for difference -19% to -52%). Both hand dominance and sex were significant covariates of response to capsaicin. CONCLUSIONS: It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glialmediated treatments for neuropathic pain. The differences in flare response between limbs may represent a useful biomarker to further investigate neuropathic pain. Inclusion of a positive control is imperative for the assessment of novel therapies for neuropathic pain.
dc.description.statementofresponsibilityNicole M. Sumracki, Mark R. Hutchinson, Melanie Gentgall, Nancy Briggs, Desmond B. Williams and Paul Rolan
dc.identifier.citationPLoS One, 2012; 7(6):1-8
dc.identifier.doi10.1371/journal.pone.0038525
dc.identifier.issn1932-6203
dc.identifier.issn1932-6203
dc.identifier.orcidHutchinson, M. [0000-0003-2154-5950]
dc.identifier.urihttp://hdl.handle.net/2440/72969
dc.language.isoen
dc.publisherPublic Library of Science
dc.rightsCopyright: © 2012 Sumracki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.source.urihttps://doi.org/10.1371/journal.pone.0038525
dc.subjectHumans
dc.subjectPain
dc.subjectSciatica
dc.subjectHyperalgesia
dc.subjectgamma-Aminobutyric Acid
dc.subjectCapsaicin
dc.subjectMinocycline
dc.subjectTreatment Outcome
dc.subjectDrug Therapy, Combination
dc.subjectInjections, Intradermal
dc.subjectAnalysis of Variance
dc.subjectCross-Over Studies
dc.subjectDouble-Blind Method
dc.subjectTime Factors
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectPregabalin
dc.titleThe effects of pregabalin and the glial attenuator minocycline on the response to intradermal capsaicin in patients with unilateral sciatica
dc.typeJournal article
pubs.publication-statusPublished

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