Analgesic efficacy of tramadol in cats with naturally occurring osteoarthritis

PLoS One. 2017 Apr 12;12(4):e0175565. doi: 10.1371/journal.pone.0175565. eCollection 2017.

Abstract

Objectives: This study aimed to (1) compare outcome assessments in normal and osteoarthritic cats and (2) evaluate the analgesic efficacy of tramadol in feline osteoarthritis (OA), in a prospective, randomised, blinded, placebo-controlled, crossover design.

Methods: Twenty cats were included after clinical examination, blood work and full body radiographs were performed. In Phase 1, outcome assessments aimed to differentiate normal (n = 5; i.e. exempt of any radiographic and clinical sign of OA) from OA (n = 15) cats. In Phase 2, OA cats were treated twice daily with a placebo (PG: cornstarch 15 mg) or tramadol (TG: 3 mg/kg) orally for 19 days, with a 3-month washout period between treatments. Evaluations were performed in normal and OA cats at baseline and consisted of: 1) peak vertical force (PVF) after staircase exercise; 2) telemetered night-time motor activity (NMA); and 3) response to mechanical temporal summation (RMTS). After treatment, PVF, NMA and RMTS evaluations were repeated in OA cats. Data were analysed with mixed model methods with an alpha-threshold of 5%.

Results: Phase 1: 1) PVF (% of body weight; mean ± SD) was higher in normal (59 ± 10.5) than in OA cats (50.6 ± 5.7) (p = 0.005); 2) NMA (no unit) was not different between groups; 3) RMTS (number of stimuli; median (range)) was higher in normal [29.5 (23.5-30)] than in OA cats [14 (8.5-28)] (p < 0.0001). Phase 2: PVF, NMA and RMTS presented a treatment effect (p = 0.024, p = 0.008 and p = 0.018, respectively). No clinically important adverse-effects were observed.

Conclusion: Outcome assessments such as kinetics (PVF) and evaluation of central sensitisation (RMTS) are discriminant of OA status. Mobility measured by NMA was not discriminant of OA status, however it increased in OA cats with tramadol treatment. Nociceptive hypersensitivity quantified by RMTS was evident in OA cats and was responsive to tramadol treatment.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Analgesics, Opioid / therapeutic use*
  • Animals
  • Cat Diseases / drug therapy*
  • Cats
  • Cross-Over Studies
  • Female
  • Male
  • Osteoarthritis / drug therapy
  • Osteoarthritis / veterinary*
  • Prospective Studies
  • Single-Blind Method
  • Tramadol / pharmacology
  • Tramadol / therapeutic use*
  • Treatment Outcome

Substances

  • Analgesics, Opioid
  • Tramadol

Grants and funding

This study was funded (Pr. Eric Troncy) in part by a Morris Animal Foundation Grant (#D09FE-803A), “TOP-CAT: Tracking Osteoarthritis Pain in the CAT”, by a Discovery grant (#441651–2013 supporting salaries) and a Collaborative Research and Development grant (#RDCPJ 418399–2011, #RDCPJ 491953–2016 supporting operations and salaries in partnership with ArthroLab Inc.) from the Natural Sciences and Engineering Research Council (NSERC) of Canada, as well as by an ongoing New Opportunities Fund grant (#9483) and a Leader Opportunity Fund grant (#24601), supporting pain/function equipment, from the Canada Foundation for Innovation. Funding for the clinical trial study was provided by a grant from Elanco Animal Health, a division of Eli Lilly and company. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. Dr. Beatriz Monteiro is the recipient of a Vanier Canada Graduate Scholarship. Dr. Mary Klinck was the recipient of an Alexander Graham Bell NSERC Canada Graduate Scholarship for Master’s research, of a Zoetis – Morris Animal Foundation (#D10-901) Doctoral Fellowship. Dr. Maxim Moreau received a Doctoral Scholarship from the Fonds de recherche du Québec-Santé, and a Doctoral Scholarship from the Canadian Institutes of Health Research – MENTOR Strategic Training Initiative in Health Research Program. Dr. Martin Guillot was the recipient of an Alexander Graham Bell NSERC Canada Graduate Scholarship for Doctorate research, and a Doctoral Scholarship from the Canadian Institutes of Health Research – MENTOR Strategic Training Initiative in Health Research Program.