title: Nociceptive stimuli responses at different levels of general anaesthesia and genetic variability.
abstract: BACKGROUND
  Changes in skin conductance (SC), clinical stress score (CSS), the bispectral index spectroscopy (BIS) index and the variation in the BIS index may be used to monitor responses to nociceptive stimuli. We wanted to examine these methods during noxious stimulation during general anaesthesia and if the responses were associated with variability in genes related to pain.
  
  
  METHODS
  Sixty patients, given propofol to a BIS level of 40-50, were stimulated with standardised tetanic electrical stimuli during propofol infusion, plasma level of 3 μg/ml alone, or together with remifentanil target plasma level of 3 ng/ml or 10 ng/ml. The CSS, SC, BIS index and the variability of the BIS index were registered. The inter-individual variation in nociceptive responses was analysed for co-variation with genotypes of 89 single nucleotide polymorphisms from 23 candidate genes.
  
  
  RESULTS
  During tetanic stimuli, CSS and SC increased significantly and were attenuated with increasing level of remifentanil, different from the BIS index and the variation in the BIS index. Polymorphisms in the P-glycoprotein (ABCB1), tachykinin 1 receptor (TACR1), dopamine receptor D3 (DRD3) and beta arrestin 2 (ARRB2) genes were associated with the co-variation in SC variables or CSS response or both during standardised nociceptive stimuli (P < 0.05). Because of no corrections for multiple testing, the genetic analyses are explorative, and associations must be tested in further studies.
  
  
  CONCLUSIONS
  This exploratory study suggests genes that may be tested further with relation to nociceptive response during anaesthesia. SC and CSS may be useful tools for monitoring nociceptive response during general anaesthesia.
authors.affiliation: Rikshospital and Ullevaal University Hospital, University of Oslo, Sognsvannsveien 20, Oslo, Norway. hanne.storm@medisin.uio.no
authors.forename: H
authors.initials: H
authors.lastname: Storm
authors.forename: R
authors.initials: R
authors.lastname: Støen
authors.forename: P
authors.initials: P
authors.lastname: Klepstad
authors.forename: F
authors.initials: F
authors.lastname: Skorpen
authors.forename: E
authors.initials: E
authors.lastname: Qvigstad
authors.forename: J
authors.initials: J
authors.lastname: Raeder
mesh_terms: D000768:Anesthesia, General; D018686:Anesthetics, Intravenous / Q000097:blood; D019540:Area Under Curve; D056805:Consciousness Monitors; D004558:Electric Stimulation; D005260:Female; D005712:Galvanic Skin Response; D014644:Genetic Variation; D005838:Genotype; D013509:Gynecologic Surgical Procedures; D006801:Humans; D007206:Individuality; D010535:Laparoscopy; D009119:Muscle Contraction / Q000187:drug effects; D059225:Nociception / Q000187:drug effects*; D010146:Pain / Q000235:genetics*; D010147:Pain Measurement / Q000379:methods*; D010880:Piperidines / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D011229:Preanesthetic Medication; D000077208:Remifentanil
chemical_list: D018686:Anesthetics, Intravenous; D010880:Piperidines; D000077208:Remifentanil