Abstracts / Scandinavian Journal of Pain 5 (2014) 207–213brospinal ﬂuid (CSF) samples from a well-deﬁned patient cohortsuffering from neuropathic pain as compared to controls.Methods: CSF samples from patients suffering from chronicneuropathic pain (n = 14) were analyzed for cathepsin S levels usingcommercial sandwich ELISAs (DY1183, R&D Systems, Minneapolis, MN, USA). Control CSF was sampled from patients undergoingminor urological surgical procedures under spinal anaesthesia(n = 70), having no obvious pain suffering.Results: The neuropathic pain group had signiﬁcantlyhigher levels of CSF cathepsin S (median 15189 pg/mL, range3213–40,040), than the control group (median 5911 pg/mL, range1909–17,188) (p < 0.005, Mann–Whitney U-test).Conclusion: The results support the existence of microglial activation in chronic neuropathic pain patients. CSF Cathepsin S mayserve as a potential biomarker for this speciﬁc mechanism linked toneuropathic pain. In the future, Cathepsin S inhibiting drugs mightbecome a new treatment alternative for neurophatic pain.E-mail: firstname.lastname@example.org://dx.doi.org/10.1016/j.sjpain.2014.05.015Inﬂammation-reactive astrocytes can berestored with a three drug combinationE. Hansson a,∗ , L. Block b , U. Björklund a , B. Biber baDepartment of Clinical Neuroscience andRehabilitation, Institute of Neuroscience andPhysiology, University of Gothenburg, SE 413 45,Gothenburg, Swedenb Department of Anaesthesiology and Intensive CareMedicine, Institute of Clinical Sciences, TheSahlgrenska Academy, University of Gothenburg, SE413 45, Gothenburg, SwedenAims: In inﬂammation-reactive astrocytes the cell parameters,Ca2+ signalling, Na+ transporters, cytoskeleton, and release of proinﬂammatory cytokines are affected. We want to re-establish theseparameters with agents, which might have a potential to restore thecells back to a normal non-inﬂammatory level.Methods: Astrocytes in primary cultures were incubatedwith lipopolysaccharide (LPS) (10 ng/ml) for 24 h to becomeinﬂammation-reactive. Different parameters were analysed to verify this inﬂammation: Ca2+ signalling, Na+ /K+ -ATPase expression,actin ﬁlament organization, and interleukin-1beta release (IL-1␤).Results: We have used an opioid agonist, endomorphin-1, thatstimulates the Gi/o protein of the -opioid receptor, an opioidantagonist, naloxone, that inhibits the Gs protein of the -opioidreceptor in ultralow concentrations, and an anti-epileptic agent,levetiracetam, that counteracts the release of IL-1␤. The combination of these three agents managed to activate the Gi/o proteinand Na+ /K+ -ATPase activity, inhibit the Gs protein, and decrease therelease of IL-1␤. The disorganized actin ﬁlaments were restored.Conclusions: The ﬁndings that the important cell parameters inastrocytes were restored back to their normal non-inﬂammatorystate after the cells were treated with the inﬂammatory agent LPScould be of clinical signiﬁcance. It may be useful for the treatmentof neuroinﬂammation and also maybe of long-term pain. The astrocyte networks play a signiﬁcant role and therefore a well-workingintercellular Ca2+ signalling is of utmost importance.Signiﬁcance: These ﬁndings put new potential drug regimenstowards treatment of neuroinﬂammation and long-term pain intofocus.E-mail: email@example.com://dx.doi.org/10.1016/j.sjpain.2014.05.016209Experiences with an adaptive design for adose-ﬁnding study in osteoarthritisF. Miller a , M. Björnsson a , O. Svensson a,b , R.Karlsten a,c,∗aAstraZeneca R&D, Södertälje, SwedenPain Clinic, St Göran hospital, Stockholm, Swedenc Multidisciplinary Pain center, Akademiskasjukhuset, Uppsala, SwedenbAims: Many new potential medicines fail in early clinical development. AZD1386 is a TRPV1 antagonist and was developed fortreatment of osteoarthritis pain at AstraZeneca. Following preclinical studies to characterize the compound, translational studies andﬁrst time in man studies the challenge is great to select the rightdoses and study population for the ﬁrst clinical studies on efﬁcacyin phase II of the drug development process.Methods: Different design alternatives in the planning of thedose-ﬁnding study for AZD1386 in OA were analysed with regardto statistical considerations, timelines and costs for the differentoptions.Results: Based on datasimulations and cost/beneﬁt analysis a 4week study with adaptive design with interim analysis at 2 weeksfor possible dose adjustment or futility stop was chosen. The studywas initiated with AZD1386 at to doses 30 and 90 mg and placebo.Based on the fact that the one-sided p-value for the primary analysis(comparison of 90 mg versus placebo) was 0.2891 and larger than0.2, the data monitoring committee decided that the study was tobe stopped after the interim analysis due to lack of efﬁcacy.Conclusions: The chosen adaptive design in this Phase IIa/bstudy enabled an early futility stop. This meant several advantages. Further exposure of patients of a non-efﬁcacious drug couldbe stopped and resources could be re-allocated earlier as well asmonetary savings.E-mail: firstname.lastname@example.org://dx.doi.org/10.1016/j.sjpain.2014.05.017Proteins with potential role in analgesic effectof spinal cord stimulation on neuropathic painA. Lind a,∗ , P. Emami b , M. Sjödin c , L. Katila a , M.Wetterhall c , K. Kultima b , T. Gordh aaDepartment of Surgical Sciences, UppsalaUniversity, Uppsala, Swedenb Department of Medical Sciences, CancerPharmacology and Computational Medicine,Uppsala University, Uppsala, Swedenc Department of Analytical Chemistry, UppsalaUniversity, Uppsala, SwedenAims: We aimed to ﬁnd proteins of relevance to the prolongedanalgesic effect of spinal cord stimulation (SCS) for patients withneuropathic pain.Methods: The proteomes of cerebrospinal ﬂuid (CSF) from 14neuropathic pain patients using spinal cord stimulation (SCS) wascompared to the CSF proteomes of the same patients when notusing the stimulator. Samples were analyzed by dimethyl label andlabel free shotgun proteomics approach. Samples were preparedby immunoafﬁnity fractionation and then separated by reversedphase nanoliquid chromatography coupled to an electrosprayionization source and analyzed by high resolution tandem massspectrometry. The proteins were comparatively quantiﬁed on thepeptide level and ranked based on numbers of regulated peptides.Then the dimethyl and label free analysis results were combined. Inorder to group proteins by function and interactions, a functional
Scandinavian Journal of Pain – de Gruyter
Published: Jul 1, 2014
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