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. Department 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