Sumracki, N.Hutchinson, M.Gentgall, M.Briggs, N.Williams, D.Rolan, P.Ikeda, K.2012-09-032012-09-032012PLoS One, 2012; 7(6):1-81932-62031932-6203http://hdl.handle.net/2440/72969BACKGROUND: 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.enCopyright: © 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.HumansPainSciaticaHyperalgesiagamma-Aminobutyric AcidCapsaicinMinocyclineTreatment OutcomeDrug Therapy, CombinationInjections, IntradermalAnalysis of VarianceCross-Over StudiesDouble-Blind MethodTime FactorsAdultMiddle AgedFemaleMalePregabalinJournal article002011970910.1371/journal.pone.00385250003053517000412-s2.0-8486200194524234Hutchinson, M. [0000-0003-2154-5950]