122Abstracts / Scandinavian Journal of Pain 12 (2016) 117–124ADRB2, pain and opioids in mice and manO. Kambur 1,2,∗ , A. Samoshkin 3,4 , M. Kaunisto 5 ,J.S. Wieskopf 3,6 , J.S. Mogil 3,6 , L. Diatchenko 3,4,7 ,E. Kalso 1,81Pharmacology, University of Helsinki, Faculty ofMedicine, Helsinki, Finland2 Department of Pain Research and Management,Oslo University Hospital, Oslo, Norway3 Alan Edwards Centre for Research on Pain, McGillUniversity, Montreal, QC, Canada4 Department of Anesthesia, McGill University,Montreal, QC, Canada5 Institute for Molecular Medicine Finland (FIMM),University of Helsinki, Helsinki, Finland6 Department of Psychology, McGill University,Montreal, QC, Canada7 Faculty of Dentistry, McGill University, McGillUniversity, Montreal, QC, H3A 1G1, Canada8 Helsinki University Central Hospital (HUCH), PainClinic, Helsinki, FinlandE-mail address: email@example.com (O. Kambur).Aims. We aim to characterize the effects of variation withinADRB2-gene on pain and opioid requirements in human patients.We will assess ADRB2-OPRM1-6TM heterodimer as a molecularmechanism, potentially explaining pronociceptive and antianalgetic effects, using preclinical in vitro and in vivo models. We willfurther assess clinical signiﬁcance via its genetic proxy, rs563649in humans.Methods. In humans, experimental and postoperative painand opioid responses were assessed in 1000 breast cancer surgery patients. Association of ADRB2 (n = 40) and OPRM1 (n = 1)polymorphisms was assessed using linear regression and analysisof variances (ANOVA). In vitro methods involved immunoﬂuorescence microscopy (IF), cellular localization and translocationof 6TM/␤2AR-heterodimers and Ca2+ -measurements. Behavioralin vivo characterization was performed in mice using formalin, vonFrey, hot plate and cold plate tests after administration of morphine, speciﬁc OPRM1-6TM agonist IBNtxA and ADRB2-antagonistICI118,551.Results. In humans, several ADRB2 SNPs were associated withpain and opioid phenotypes. The strongest associations were seenbetween cold pain phenotypes and rs17108817 & rs11957757(p < 0.0001). In vitro, coexpression with ␤2 -Ars increased translocation of 6TM-MOR to plasma membrane and Ca2+ responses aftertreatment with selective 6TM-agonist, IBNtxA, compared with thecells expressing OPRM1-6TM alone. In vivo, co-administration of␤2 AR selective antagonist ICI 118,551 increased analgesic efﬁcacyof opioids in a synergistic manner and reduced opioid-inducedhyperalgesia.Conclusions. Our ﬁndings suggest that ADRB2 and geneticvariation in ADRB2-gene are involved in the modulation of humanpain and opioid responses. 6TM-MOR/␤2 -AR heterodimerizationrepresents a molecular mechanism causing excitatory cellulareffects and sufﬁcient explanatory potential to explain pronociceptive and antianalgesic effects. Our animal ﬁndings furtherconﬁrmed the concept of ␤2 -AR and 6TM-MOR interaction in vivo.We suggest that co-administration of ␤-blockers with opioidsmight increase efﬁcacy and safety of OPRM1 agonists.http://dx.doi.org/10.1016/j.sjpain.2016.05.016Retrospective analysis of pediatric patients withCRPSL. Kiehelä ∗ , J. Pouttu, K. HamunenHelsinki University Hospital (HUH), Department ofanesthesiology and intensive care, Pain Clinic,FinlandE-mail address: lauri.kiehela@hus.ﬁ (L. Kiehelä).Aims: The aim of the study was to describe the clinical featuresand clinical pathway of pediatric CRPS patients in HUH Children’sHospital.Methods: This retrospective study included patients admittedto the pediatric pain clinic for CRPS during six years 2008–2013.Data on time from the ﬁrst symptoms to diagnosis, ﬁrst appointment at the pain clinic, and symptom resolution, as well asdemographic and clinical symptoms were extracted from patientrecords.Results: Forty patients were clinically diagnosed with CRPSduring the time period without using the Budapest Criteria. 75% ofthe patients were female, median age was 12, and in 90% of the casesthe CRPS was localized in the lower extremity. The median timefrom ﬁrst symptoms to the CRPS diagnosis was 8.5 weeks (range0–47), to ﬁrst appointment with the pain physician 10 weeks (range2–47), and to symptom resolution 35 weeks (range 10–131). Elevenout of forty patients (27.5%) were not symptom-free at the end ofthe treatment period. Most common clinical ﬁnding was allodyniaor hyperalgesia of the afﬂicted area (70%).Conclusions: Compared to an earlier study performed in ourhospital (retrospective study of seven years, n = 18), the number ofpatients has more than doubled, maybe due to better awarenessof the syndrome. Our ﬁndings about demographics and localization of CRPS are in agreement with previous literature. Time toreaching diagnosis, the small number of consultations and radiographs show that CRPS is well known among pediatric orthopedicsurgeons. Many Budapest criteria that are now considered important diagnostic ﬁndings were not highly prevalent in our patients(e.g. prior trauma, color changes of skin), although patient recordswere not always clear about the ﬁndings leading to diagnosis. TheBudapest criteria should be used to standardize the diagnosis alsoin our pediatric patients.http://dx.doi.org/10.1016/j.sjpain.2016.05.017Activation of epidermal growth factor receptors(EGFRs) following disc herniation induceshyperexcitability in the pain pathwaysM. Kongstorp, A. Moen, D.P. Jacobsen, F. Haugen,A. Mahmood, J. Gjerstad ∗The National Institute of Occupational Health, Oslo,NorwayE-mail address: Johannes.Gjerstad@stami.no (J. Gjerstad).Aims: Low back pain and sciatica after disc herniation may becaused by mechanical compression of the nerve roots, but also bythe release of pro-inﬂammatory agents including growth factorsfrom the nucleus pulposus (NP).Methods: Here, in an animal model mimicking the clinical situation following disc herniation, CLIA protein analyses, extracellularsingle-cell recordings in the spinal dorsal horn and qPCR were performed to examine the nociceptive signaling due to disc herniation.Results: The present data demonstrated that EREG may be released from NP – and that administration of EREG onto the spinaldorsal nerve roots increased spontaneous activity in nociceptiveneurons. An up-regulation of EGFR and HER4 in the dorsal horn as
Scandinavian Journal of Pain – de Gruyter
Published: Jul 1, 2016
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