title: Evaluation of clinical and inflammatory profile in opioid addiction patients with comorbid pain: results from a multicenter investigation.
abstract: BACKGROUND
  Chronic pain is the most commonly reported comorbidity among patients with opioid addiction receiving methadone maintenance treatment (MMT), with an estimated prevalence ranging between 30% and 55%. Evidence suggests that patients with comorbid pain are at high risk for poor treatment response, including continued illicit substance use. Due to the important relationship between the presence of pain and illicit substance abuse within the MMT setting, it is imperative that we target our efforts toward understanding the characteristics of this patient population.
  
  
  METHODS
  The primary objective of this study was to explore the clinical and inflammatory profile of MMT patients reporting comorbid pain. This multicenter study enrolled patients (n=235) on MMT for the treatment of opioid dependence. Clinical history and blood and urine data were collected. Blood samples were obtained for estimating the serum levels of inflammatory markers (tumor necrosis factor [TNF]-α, interleukin-1 receptor antagonist [IL-1ra], IL-6, IL-8, IL-10, interferon [IFN]-γ and chemokine (C-C motif) ligand 2 [CCL2]). The study objectives were addressed using a descriptive statistical summary and a multivariable logistic regression model constructed in STATA version 12.
  
  
  RESULTS
  Among the participants eligible for inclusion (n=235), serum IFN-γ level and substance abuse behavior proved to be important delineating characteristics for the detection of comorbid pain. Analysis of inflammatory profile showed IFN-γ to be significantly elevated among patients reporting comorbid pain (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.17, 3.50; P=0.01). Patients reporting comorbid pain were also found to have an increase in positive opioid urine screens (OR: 1.02; 95% CI: 1.00, 1.03; P=0.01), indicating an increase in illicit opioid consumption.
  
  
  CONCLUSIONS
  MMT patients with comorbid pain were shown to have elevated IFN-γ and higher rates of continued opioid abuse. The ability to objectively distinguish between patients with comorbid pain may help to both improve the prediction of poor responders to MMT as well as identify treatment approaches such as anti-inflammatory medications as safe alternatives for MMT patients with comorbid pain.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Brittany B
authors.initials: BB
authors.lastname: Dennis
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, McMaster University, Hamilton, ON, Canada.
authors.forename: M Constantine
authors.initials: MC
authors.lastname: Samaan
authors.affiliation: McMaster Integrative Neuroscience Discovery and Study Program, McMaster University, Hamilton, ON, Canada.
authors.forename: Monica
authors.initials: M
authors.lastname: Bawor
authors.affiliation: Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Paul
authors.affiliation: Ontario Addiction Treatment Centres, Richmond Hill, ON, Canada.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Plater
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pare
authors.affiliation: Department of Medicine, Hamilton General Hospital, Hamilton, ON, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Worster
authors.affiliation: Ontario Addiction Treatment Centres, Richmond Hill, ON, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Varenbut
authors.affiliation: Ontario Addiction Treatment Centres, Richmond Hill, ON, Canada.
authors.forename: Jeff
authors.initials: J
authors.lastname: Daiter
authors.affiliation: Ontario Addiction Treatment Centres, Richmond Hill, ON, Canada ; Northern Ontario School of Medicine, Sudbury, ON, Canada.
authors.forename: David C
authors.initials: DC
authors.lastname: Marsh
authors.affiliation: Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada.
authors.forename: Dipika
authors.initials: D
authors.lastname: Desai
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada ; Centre for Evaluation of Medicine, Hamilton, ON, Canada ; System Linked Research Unit, Hamilton, ON, Canada.
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada ; Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada ; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Samaan
keywords: Brief Pain Inventory; CCL2; IFN-γ; TNF-α; inflammatory markers; interleukins; methadone maintenance treatment; opioid dependence