title: Study protocol for a pilot, randomised, double-blinded, placebo controlled trial of perineural local anaesthetics and steroids for chronic post-traumatic neuropathic pain in the ankle and foot: the PREPLANS study.
abstract: Peripheral neuropathic pain (PNP) associated with trauma is often refractory to treatment. Administration of local anaesthetics (LA) and steroids around injured nerves has been proposed as an option for patients unresponsive to conventional treatments for refractory PNP following trauma. There is insufficient evidence to support a large, potentially expensive, full-scale randomised controlled trial (RCT) that involves comparison of effects of perineural steroids and LA against LA or saline injections on analgesia, physical and psychological functioning, and quality of life. There is also a lack of data that would allow estimation of analgesic efficacy or sample size for the full-scale RCT. The objective of this pilot RCT is to yield information to support planning of a full-scale RCT in this population.
  
  
  
  30 participants with post-traumatic PNP in the ankle and foot of moderate-to-severe intensity and duration of more than 3 months will be enrolled in this pilot RCT. Participants will be randomised to receive three ultrasound-guided perineural injections of 0.9% saline, 0.25% bupivacaine (a long-acting LA) or a combination of 0.25% bupivacaine and a steroid (methylprednisolone 16 mg per nerve) at weekly intervals. The primary objectives are to determine the feasibility and sample size of a full-scale RCT in this population. The secondary objectives are to evaluate the effect of study interventions on analgesia, persistence of neuropathic pain, psychological and physical function, quality of life and participants' global impression of change at 1 and 3 months after the interventions. In addition, adverse effects associated with perineural injections and with systemic absorption of steroids will also be recorded.
  
  
  
  The protocol was approved by the University Health Network Research Ethics Board (UHN REB number 15-9584-A). The results will be disseminated in peer-reviewed journals and at scientific conferences.
  
  
  
  NCT02680548; Pre-results.
authors.affiliation: Department of Anesthesia and Pain Management and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada Department of Anesthesia and Pain Management, University Health Network-Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: Anuj
authors.initials: A
authors.lastname: Bhatia
authors.affiliation: Department of Neurology, University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Vera
authors.initials: V
authors.lastname: Bril
authors.affiliation: Department of Anesthesia, University Health Network-Toronto Western Hospital and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Brull
authors.affiliation: Health Care and Outcomes Research, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada Institute of Health Policy, Management & Evaluation, and Toronto Musculoskeletal Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Perruccio
authors.affiliation: Department of Anesthesia, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada Department of Anesthesia, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Duminda
authors.initials: D
authors.lastname: Wijeysundera
authors.affiliation: Department of Anesthesia and Pain Management, University Health Network-Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: Sabeeh
authors.initials: S
authors.lastname: Alvi
authors.affiliation: Division of Orthopaedic Surgery, Foot and Ankle Program, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Johnny
authors.initials: J
authors.lastname: Lau
authors.affiliation: Division of Orthopaedic Surgery, Arthritis Program, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Gandhi
authors.affiliation: Health Care and Outcomes Research, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada Division of Orthopaedic Surgery, Department of Surgery and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahomed
authors.affiliation: Health Care and Outcomes Research, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada Department of Physical Therapy and Surgery, Graduate Department of Rehabilitation Science, the Institute of Health Policy, Management and Evaluation and Institute of Medical Science, Toronto, Ontario, Canada.
authors.forename: Aileen M
authors.initials: AM
authors.lastname: Davis
mesh_terms: D000779:Anesthetics, Local / Q000009:adverse effects / Q000627:therapeutic use*; D000842:Ankle / Q000294:innervation*; D016512:Ankle Injuries / Q000150:complications; D002045:Bupivacaine / Q000009:adverse effects / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy / Q000209:etiology; D004311:Double-Blind Method; D005240:Feasibility Studies; D005528:Foot / Q000294:innervation*; D018409:Foot Injuries / Q000150:complications; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007267:Injections; D008775:Methylprednisolone / Q000009:adverse effects / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D010865:Pilot Projects; D011788:Quality of Life
chemical_list: D000779:Anesthetics, Local; D005938:Glucocorticoids; D008775:Methylprednisolone; D002045:Bupivacaine
keywords: neuropathic pain; perineural; steroids