title: Acute pain Factors predictive of post-operative pain and opioid requirement in multimodal analgesia following knee replacement.
abstract: BACKGROUND
  Despite the development of multimodal analgesia for postoperative pain management, opioids are still required for effective pain relief after knee arthroplasty. We aimed to identify the determinants of post-operative pain intensity and post-operative opioid requirement in this context.
  
  
  METHODS
  In this observational prospective study, we recorded patient characteristics, pre-operative pain intensity, anxiety and depression levels, sensitivity and pain thresholds in response to an electrical stimulus, and mu-opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT) single-nucleotide polymorphisms. Multivariate linear regression models were used to identify predictors of post-operative pain at rest and opioid requirement.
  
  
  RESULTS
  We included 109 patients. Pre-operative pain at rest (p = 0.047), anxiety level (p = 0.001) and neuropathic pain symptoms (p = 0.030) were independently and positively associated with mean post-operative pain intensity adjusted for mean post-operative morphine equivalent dose (MED). Mean post-operative pain intensity at rest was lower (p = 0.006) in patients receiving celecoxib and pregabalin in the post-operative period, with all other variables constant. Mean post-operative MED over 5 days was low, but highly variable (78.2 ± 32.1 mg, from 9.9 to 170 mg). Following adjustment for mean post-operative pain intensity, it was independently negatively correlated with age (p = 0.004), and positively correlated with associated paracetamol treatment (p = 0.031). No genetic effect was detected in our sample.
  
  
  CONCLUSIONS
  Our findings suggest that clinicians could use the pre-operative pain profile, in terms of anxiety levels, neuropathic pain symptoms, and chronic pre-operative pain intensity, to improve the efficacy of pain management after knee surgery.
authors.affiliation: INSERM 987, Physiopathologie et pharmacologie clinique de la douleur, Ambroise Paré, Paris, France.|Assistance Publique-Hôpitaux de Paris, Therapeutic Research Unit, Department of Internal Medicine, Hôpital Lariboisière, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Thomazeau
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Biostatistics and Epidemiology Department, Hôpital Hôtel Dieu, Paris, France.|INSERM U1178, Mental Health and Public Health, Paris-Sud and Paris Descartes Universities, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Rouquette
authors.affiliation: INSERM 987, Physiopathologie et pharmacologie clinique de la douleur, Ambroise Paré, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Martinez
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de chirurgie orthopédique et traumatologique, Hôpital Lariboisière, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Rabuel
authors.affiliation: INSERM U1144, Variabilité de réponse aux psychotropes, Universités Paris Descartes and Paris Diderot, France.
authors.forename: N
authors.initials: N
authors.lastname: Prince
authors.affiliation: INSERM U1144, Variabilité de réponse aux psychotropes, Universités Paris Descartes and Paris Diderot, France.
authors.forename: J L
authors.initials: JL
authors.lastname: Laplanche
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de chirurgie orthopédique et traumatologique, Hôpital Lariboisière, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Nizard
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Therapeutic Research Unit, Department of Internal Medicine, Hôpital Lariboisière, Paris, France.|INSERM U1144, Variabilité de réponse aux psychotropes, Universités Paris Descartes and Paris Diderot, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Bergmann
authors.affiliation: INSERM 987, Physiopathologie et pharmacologie clinique de la douleur, Ambroise Paré, Paris, France.|Centre d'Evaluation et de Traitement de la Douleur, Hôpital Hôtel Dieu, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Perrot
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Therapeutic Research Unit, Department of Internal Medicine, Hôpital Lariboisière, Paris, France.|INSERM U1144, Variabilité de réponse aux psychotropes, Universités Paris Descartes and Paris Diderot, France.
authors.forename: C
authors.initials: C
authors.lastname: Lloret-Linares
mesh_terms: D059787:Acute Pain / Q000503:physiopathology* / Q000523:psychology; D000368:Aged; D000577:Amides / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000779:Anesthetics, Local / Q000627:therapeutic use; D001007:Anxiety / Q000523:psychology; D019645:Arthroplasty, Replacement, Knee; D002394:Catechol O-Methyltransferase / Q000235:genetics; D000068579:Celecoxib / Q000627:therapeutic use; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D003863:Depression / Q000523:psychology; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use; D015999:Multivariate Analysis; D009407:Nerve Block; D059408:Pain Management; D017288:Pain Threshold; D010149:Postoperative Pain / Q000188:drug therapy* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D000069583:Pregabalin / Q000627:therapeutic use; D057234:Preoperative Period; D011446:Prospective Studies; D017450:Receptors, Opioid, mu / Q000235:genetics; D000077212:Ropivacaine; D012720:Severity of Illness Index
chemical_list: D000577:Amides; D000700:Analgesics; D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D052246:Cyclooxygenase 2 Inhibitors; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D000069583:Pregabalin; D009020:Morphine; D000077212:Ropivacaine; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D000068579:Celecoxib