Why it matters

Surgeries from Orthopedics and Traumatology rank amongst the most painful interventions overall. Millions of musculoskeletal surgeries are performed annually and this number is increasing. Achieving adequate pain relief after musculoskeletal surgery is a major challenge. To date, opioids fulfil a central role in the treatment of postoperative pain, but there are increasing concerns about their use. Toxic side-effects of the systemic use of opioids can lead to insufficient relief of pain, malnutrition, delayed mobilization and unnecessary long hospital stay. Furthermore, opioids can be highly addictive even after relatively short periods of use.

Most painful interventions

Musculoskeletal surgical procedures are amongst the most painful surgical interventions. A study performed in 2013 analyzed and ranked postoperative pain in 179 different types of surgery. Seven of the top ten most painful surgical procedures were either orthopedic or traumatologic interventions.1 The pain experienced by patients is presumably caused by injury to the periosteum, a thin layer around the bone with a high density of sensory innervation.2

Number of surgeries is increasing

Due to an aging population and increased prevalence of obesity, the worldwide prevalence of debilitating musculoskeletal conditions, for example osteoarthritis, is growing. As a result, the annual number of orthopedic surgical interventions is increasing. Currently, 438.000 total hip arthroplasties (THA’s) and 686.000 total knee arthroplasties (TKA’s) are performed each year in the United States. These numbers are expected to increase to 850.000 THA’s and 1.920.000 TKA’s by the year 2030.3 Furthermore, the US number of spinal fusion surgeries increased from 174.223 to 413.171 between the years 1998 and 2008, and this number is also expected to grow.4 Similar trends are expected in Europe.

Pain treatment is a major challenge

Adequate pain management remains one of the most challenging aspects of postoperative treatment and can presently be considered an unmet clinical need. Moderate to severe postoperative pain is commonly reported both early (up to 6 days) and late (up to 14 days) in the postoperative period.5 Inadequate postoperative pain management is reported in up to 75% of patients.6

Increasing concerns with opioids

Opioids play an important role in most multimodal pain regimens. The use of opioids, however, comes with many drawbacks. Firstly, the use of opioids is associated with systemic side-effects, including nausea, vomiting, constipation, urinary retention, bowel dysfunction, dizziness, respiratory depression and decreased cognitive function.7 Secondly, opioids can be highly addictive and preventing their continued use remains a major challenge amongst health-care providers.8 In 2017, the U.S. Status of Health and Human Services (HHS) declared a public health emergency and announced a 5-point strategy to combat the so-called ‘Opioid Crisis’.9

Long hospital stay

Over the past two decades, recognizing the importance of fast recovery after musculoskeletal surgery has gained in popularity. Numerous studies have shown that early mobilization leads to reduced hospital stay, less morbidity and better overall convalescence.10 For total hip arthroplasty procedures, the introduction of ‘enhanced recovery after surgery’ (ERAS) protocols has led to a reduction in mean length of hospital stay from 3.8 days in 2006-2009 to 2.7 days in 2014-2016.11 The length of hospital stay currently depends greatly on the pain treatment related side-effects experienced by the patient.


1. Gerbershagen HJ, Aduckathil S, van Wijck AJM, et al: Pain Intensity on the First Day after Surgery. Anesthesiology 118:934–944, 2013

2. Nencini S, Ivanusic JJ: The physiology of bone pain. How much do we really know? Front Physiol 7:1–15, 2016

3. Singh JA, Yu S, Chen L, et al: Rates of Total Joint Replacement in the United States: Future Projections to 2020–2040 Using the National Inpatient Sample [Internet]. J Rheumatol jrheum.170990, 2019Available from: http://www.jrheum.org/lookup/doi/10.3899/jrheum.170990

4. Rajaee SS, Bae HW, Kanim LEA, et al: Spinal fusion in the United States: Analysis of trends from 1998 to 2008. Spine (Phila Pa 1976) 37:67–76, 2012

5. Roberts M, Brodribb W, Mitchell G: Reducing the Pain: A Systematic Review of Postdischarge Analgesia Following Elective Orthopedic Surgery. Pain 711–727, 2012

6. Joshi GP, Ogunnaike BO: Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain. Anesthesiol Clin North America 23:21–36, 2005

7. Richard Kessler E, Shah M, Gruschkus SK, et al: Cost and quality implications of opioid-based postsurgical pain control using administrative claims data from a large health system: Opioid-Related adverse events and their impact on clinical and economic outcomes. Pharmacotherapy 33:383–391, 2013

8. Colvin LA, Bull F, Hales TG: Perioperative opioid analgesia—when is enough too much? A review of opioid-induced tolerance and hyperalgesia [Internet]. Lancet 393:1558–1568, 2019Available from: https://linkinghub.elsevier.com/retrieve/pii/S0140673619304301


10. Kehlet H: Fast-track hip and knee arthroplasty. Lancet 381:1600–1602, 2013

11. Grosso MJ, Neuwirth AL, Boddapati V, et al: Decreasing Length of Hospital Stay and Postoperative Complications after Primary Total Hip Arthroplasty: A Decade Analysis From 2006 to 2016 [Internet]. J Arthroplasty , 2018Available from: https://linkinghub.elsevier.com/retrieve/pii/S0883540318311185

Dr. Vaccaro has served as the president of the Rothman Orthopaedic Institute since 2014, and is the Richard H. Rothman Professor and Chairman in the Status of Orthopaedic Surgery, and Professor of Neurosurgery at Thomas Jefferson University in Philadelphia, Pennsylvania.

He is the President-elect of Cervical Spine Research Society (CSRS), 2019. He was the recipient of the Leon Wiltse award given for excellence in leadership and clinical research for spine care by the North American Spine Society (NASS) and is the past President of the American Spinal Injury Association and the Association for Collaborative Spine Research.

He has over 730 peer reviewed and 200 non-peer reviewed publications.  He has published over 346 book chapters and is the editor of over 55 textbooks and co-editor of OKU-Spine I and editor of OKU-8.  Dr. Vaccaro also serves as Co-Director of the Regional Spinal Cord Injury Center of the Delaware Valley and  Co-Director of Spine Surgery and the Spine Fellowship program at Thomas Jefferson University Hospital, where he instructs current fellows and residents in the diagnosis and treatment of various spinal problems and disorders.


Raymond Schiffelers is professor of Nano Medicine at the faculty Clinical Chemistry and Hematology at the UMC Utrecht. He is specialized in drug delivery and drug targeting. Currently he coordinates the H2020 B-Smart program and participates in several EU and national projects on nano-medicine.


Professor Jos Malda is Head of Research at the Status of Orthopaedics, University Medical Center Utrecht and the Status of Equine Sciences, University of Utrecht. He also leads the Utrecht Biofabrication Facility. He is a long-standing Board member of the International Cartilage Repair Society and President of the International Society for Biofabrication.


Marianna Tryfonidou is professor of the Orthopaedics section of the department of Clinical Sciences of Companion Animals.

She is a specialist veterinary surgeon for companion animals and researcher into tissue regeneration. She coordinates theiPSpineproject that was recently awarded €15 million under the Horizon 2020 programme, towards researching a solution for chronic lower back pain.


Bas Oosterman is co-founder and CEO of SentryX.

Before he served as Chief Operating Officer of Julius Clinical and worked for Philips Electronics in various positions. He studied econometrics, received his PhD degree in Management and Organization, and is a (six sigma) Black Belt. His PhD thesis dealt with speeding up the time-to-market of new product innovation projects.


Jorrit-Jan Verlaan is co-founder and CTO/CMO of SentryX.

Sinds 2010 is dr. Verlaan werkzaam als orthopedisch chirurg in het UMC Utrecht. In hetzelfde centrum is hij (cum laude) gepromoveerd en opgeleid. Afwijkingen van de wervelkolom op basis van ongevallen, stofwisselingsziekten en, voornamelijk, oncologische aandoeningen behoren tot zijn terrein. Dr. Verlaan is actief in basale en toegepaste wetenschap en begeleidt meerdere PhD-studenten. Hij is (co-)auteur van meer dan 75 internationale peer-reviewed artikelen en vijftien hoofdstukken in internationale vakboeken. In de functie van opleider draagt hij zorg voor de ontwikkeling van assistenten in opleiding tot orthopedisch chirurg.