title: Intra-articular onabotulinumtoxinA in osteoarthritis knee pain: effect on human mechanistic pain biomarkers and clinical pain.
abstract: OBJECTIVE
  OnabotulinumtoxinA (onabotA) attenuates peripheral nociceptive transduction and consequently neuronal firing. The aim of this mechanistic study was to evaluate the effect of intra-articular (IA) onabotA in patients with painful knee osteoarthritis (OA).
  
  
  METHODS
  We conducted a double-blind, randomized, placebo-controlled, 12-week trial using a single ultrasound-guided IA injection of onabotA (200 U). Patients (N = 121) were randomized to receive onabotA (n = 61) or placebo (n = 60). Mechanistic pain biomarkers and clinical outcomes were used for profiling the effect. The biomarkers were pressure pain thresholds (PPTs) from the knee joint (localized sensitization) and extra-articular sites (widespread sensitization), and wind-up pain (central sensitization). Clinical assessments included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), average daily pain (ADP), patient global impression of change (GIC), and rescue medication. The painDETECT questionnaire (PD-Q) was used for subgrouping patients (nociceptive, neuropathic, and mixed/uncertain).
  
  
  RESULTS
  The nociceptive and non-nociceptive groups were identical with respect to all baseline data. No significant differences in clinical efficacy parameters were found between onabotA and placebo in the entire population. The nociceptive group showed significant improvement after IA onabotA at week 8 for all WOMAC outcomes, ADP at weeks 9 and 10, and patient GIC at week 12, and significant reduction in rescue medication counts within each 14-day period at weeks 9 and 10. After 4, 8, and 12 weeks, significant correlations were obtained in the onabotA group between ADP (both the entire group and the nociceptive group) and various sensitization parameters. The nociceptive group showed pronounced effects on widespread sensitization.
  
  
  CONCLUSIONS
  Intra-articular onabotA given to patients with nociceptive knee OA reduced pain sensitization together with improvement in pain and function.
authors.affiliation: a Aalborg University , SMI , Aalborg , Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.affiliation: b Sanofi Biosurgery DPU , Cambridge , MA , USA.
authors.forename: G-L
authors.initials: GL
authors.lastname: Jiang
authors.affiliation: c Allergan, Inc. , Irvine , CA , USA.
authors.forename: R
authors.initials: R
authors.lastname: DeGryse
authors.affiliation: d OticPharma, Inc , Irvine , CA , USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Turkel
mesh_terms: D065087:Acetylcholine Release Inhibitors / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D059333:Central Nervous System Sensitization; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D008297:Male; D008875:Middle Aged; D059225:Nociception; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010147:Pain Measurement; D017288:Pain Threshold; D011312:Pressure; D016896:Treatment Outcome
chemical_list: D065087:Acetylcholine Release Inhibitors; D019274:Botulinum Toxins, Type A