In November 2019, OrthoBuzz promised readers more details from the Pain Management Research Symposium held that month (see related post), which was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Those details are now available in the form of a JBJS Supplement containing 12 articles generated from that convening of > 30 orthopaedic researchers and journal editors. The Symposium focused on the unique challenges of designing studies that will answer pressing questions about pain management related to musculoskeletal conditions and procedures.
The content of this open-access Supplement ranges from subspecialty-specific considerations in pain management to “complementary medicine” approaches. It culminates in 7 key “Recommendations for Pain Management Research,” all targeted to identifying effective pain-management strategies, not just elimination of opioids. Among those recommendations are the following:
- Define all terms (such as “long-term opioid use”) precisely.
- Quantify opioid use in morphine milligram equivalents (MMEs), and state how MMEs were calculated.
- Precisely define the study population (including age, sex, and socioeconomic and cultural characteristics).
- Mental/emotional risk factors–including depression, catastrophizing, expectations, and coping ability–should be studied.
- Outcome measures should be patient-related, not just the number of pills taken.
JBJS would again like to thank NIAMS for its support and all Symposium participants and Supplement authors for their time and energy.
The public health crisis attributed to opioids has placed increasing emphasis on other approaches to pain management, both pharmacologic and nonpharmacologic. Although some people find the term “multimodal pain management” to be ambiguous when used in clinical research or patient care, it emphasizes the need for a broader (and multidisciplinary) approach to pain management.
On the pharmacologic side, pregabalin has been found to be a variably effective adjunctive analgesic in research involving joint arthroplasty. However, its use in adolescents and children has not been adequately explored. In the February 5, 2020 issue of The Journal, Helenius et al. investigate the impact of pregabalin on total opioid consumption and pain scores in a randomized, placebo-controlled trial of 63 adolescents undergoing posterior instrumented spinal-fusion procedures. These operations are quite invasive and often result in ICU admission because of the amount of narcotics required. In this study, induction and maintenance of anesthesia and mobilization protocols were standardized for patients in both the pregabalin and placebo groups, and the authors precisely measured opioid consumption during the first 48 hours after surgery with data from patient-controlled anesthesia systems.
According to the findings from this adequately powered trial, adjunctive pregabalin did not have a positive impact on opioid consumption or postoperative pain scores. Despite these negative findings, it is my hope that this drug and others being investigated as adjunctive “modes” in multimodal pain management will be subjected to similarly designed trials, so we can accurately determine which agents work best in limiting opioid utilization.
Marc Swiontkowski, MD
Designing studies to answer questions about surgical procedures takes a lot of thought, effort, and experience. Creating robust study designs to investigate pain management related to musculoskeletal conditions and procedures presents additional, unique challenges.
On November 19, 2019, more than 30 orthopaedic researchers and journal editors convened to identify—and propose solutions for—those challenges. The one-of-a-kind Pain Management Research Symposium was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS award number 1R13AR076879-01) and hosted by The Journal of Bone & Joint Surgery.
Several themes emerged from the daylong discussions and presentations:
- Despite the fact that 80% of opioid prescriptions worldwide originate in the US, outcome measures going forward should focus on effective pain management rather than reduced or “zero” opioids.
- The wide variability of definitions of key research terms such as “opioid naïve” and “persistent opioid use” makes it difficult to reach robust conclusions from prior opioid/pain management research.
- Beware false equations/assumptions. For example, opioid prescription filling is not the same as opioid consumption, and persistent opioid use after surgery does not equal iatrogenic opioid dependence.
- Surgeons and other physicians must maintain a biopsychosocial perspective on pain management. Risk factors for persistent use of opioids include mental/emotional states such as depression and catastrophizing.
- Despite some equivocal reports in the orthopaedic literature, there is no convincing evidence that NSAIDs negatively affect fracture healing. Therefore, absent specific patient contraindications, NSAIDs can be considered for pain management in trauma cases.
Many more details from the Pain Management Research Symposium will appear in a special JBJS supplement, scheduled for publication in the first half of 2020.
The Journal would again like to thank all the participants for their time and energy and NIAMS for its support.
Every month, JBJS publishes a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all such OrthoBuzz summaries.
This month, co-author Nitin B. Jain, MD, MSPH selected the most clinically compelling findings from the 40 studies summarized in the November 20, 2019 “What’s New in Orthopaedic Rehabilitation.”
–A randomized controlled trial compared pain-related function, pain intensity, and adverse effects among 240 patients with chronic back, hip, or knee pain who were randomized to receive opioids or non-opioid medication.1 After 12 months, there were no between-group differences in pain-related function. Statistically, the pain intensity score was significantly lower in the non-opioid group, although the difference is probably not clinically meaningful. Adverse events were significantly more frequent in the opioid group.
–A series of nested case-control studies found that the use of the NSAID diclofenac was associated with an increase in the risk of myocardial infarction in patients with spondyloarthritis and osteoarthritis, relative to those taking the NSAID naproxen.2
–Intra-articular injections of corticosteroids or hyaluronic acid are often used for pain relief prior to an eventual total knee arthroplasty (TKA). An analysis of insurance data found that patients who had either type of injection within three months of a TKA had a higher risk of periprosthetic joint infection (PJI) after the operation than those who had injections >3 months prior to TKA.
Partial-Thickness Rotator Cuff Tears
–A randomized controlled trial of 78 patients with a partial-thickness rotator cuff compared outcomes of those who underwent immediate arthroscopic repair with outcomes among those who delayed operative repair until completing 6 months of nonoperative treatment, which included activity modification, PT, corticosteroid injections, and NSAIDs.3 At 2 and 12 months post-repair, both groups demonstrated improved function relative to initial evaluations. At the final follow-up, there were no significant between-group differences in range of motion, VAS, Constant score, or ASES score. Ten (29.4%) of the patients in the delayed group dropped out of the study due to symptom improvement.
Stem Cell Therapy
–A systematic review that assessed 46 studies investigating stem cell therapy for articular cartilage repair4 found low mean methodology scores, indicating overall poor-quality research. Only 1 of the 46 studies was classified as excellent, prompting the authors to conclude that evidence to support the use of stem cell therapy for cartilage repair is limited by a lack of high-quality studies and heterogeneity in the cell lines studied.
- Krebs EE, Gravely A, Nugent S, Jensen AC, DeRonne B, Goldsmith ES, Kroenke K, Bair MJ, Noorbaloochi S. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018 Mar 6;319(9):872-82.
- Dubreuil M, Louie-Gao Q, Peloquin CE, Choi HK, Zhang Y, Neogi T. Risk ofcmyocardial infarction with use of selected non-steroidal anti-inflammatory drugs incpatients with spondyloarthritis and osteoarthritis. Ann Rheum Dis. 2018 Aug;77(8): 1137-42. Epub 2018 Apr 19.
- Kim YS, Lee HJ, Kim JH, Noh DY. When should we repair partial-thickness rotator cuff tears? Outcome comparison between immediate surgical repair versus delayed repair after 6-month period of nonsurgical treatment. Am J Sports Med. 2018 Apr;46(5):1091-6. Epub 2018 Mar 5.
- Park YB, Ha CW, Rhim JH, Lee HJ. Stem cell therapy for articular cartilage repair: review of the entity of cell populations used and the result of the clinical application of each entity. Am J Sports Med. 2018 Aug;46(10):2540-52. Epub 2017 Oct 12.
Several authors have described the medical-school experience as “socialization” into the medical field. Medical students often learn the scientific underpinnings simultaneously with the social processes of interviewing/dialoging, examining, and then developing a treatment plan with the patient. One “subspecialty” social process that orthopaedists learn is pain management. While we are certainly encouraged to understand the scientific basis of this important and complex topic, much of the learning comes in the form of mirroring: junior residents do what senior residents instruct them to do, while senior residents follow the direction of attendings. These passed-on habits are culturally ingrained and persistent.
As Young et al. show in the July 17, 2019 issue of The Journal, the pain-management habits learned in training vary greatly from country to country, which is not surprising. Specifically, these authors examined the prescribing of postprocedural opiates by residents in the Netherlands, Haiti, and United States. They found that US residents prescribe significantly more morphine milligram equivalents (MMEs) of opioids at patient discharge than residents from either of the other 2 countries. The authors also showed that residents from the United States were the only group prescribing a significantly greater amount of MMEs to patients younger than 40 years old than to those above the age of 70.
Many pundits pin the phenomenon of opioid overprescribing in the US on the American public’s wish to be free from discomfort, along with the aggressive marketing and advertising of these medications in the United States. While this may be true, I think Young et al. have further identified the major influence that a resident’s training environment may have on prescribing practices. As already mentioned, residents often imitate what they see from more experienced residents and attendings, but sometimes those lessons, especially in pain management, lack a scientific basis.
What is missing from this survey-based study is data on patient satisfaction with postprocedural opiate prescribing. Having been involved in clinical care in Haiti, my impression is that patients there accept the local practice of pain management, constrained as it might be by resource limitations. I suspect the same is true in the United States and the Netherlands. Regardless, these findings demand that emphasis be placed on teaching orthopaedic residents evidence-based pain-management protocols. This will require a concerted effort from teachers and mentors at all levels of our medical-education system. This investigation is an important reminder that developing solutions to the opioid overprescribing problem in the US might begin in residency, where “cultural formation” occurs.
Marc Swiontkowski, MD
There is little doubt that dramatic increases in prescriptions for opioid analgesics during the 21st century have been a major contributor to the current opioid crisis. Although primary care providers are at the front line of pain management and addiction prevention and treatment, recent research indicates that orthopaedic surgeons frequently overprescribe opioids to their patients. To help support safer prescribing, NEJM Group, through an independent educational grant and with support from Boston University School of Medicine, recently launched a NEJM Knowledge+ Pain Management and Opioids module.
The course, which contains more than 60 case-based questions on this timely and important topic, is available free of charge at https://knowledgeplus.nejm.org/pain-opioids. The activity conforms to the FDA’s Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) Education Blueprint for Health Care Providers Involved in the Treatment and Monitoring of Patients with Pain.
Many of the case-based questions in the module are geared toward primary care physicians, but approximately 50% of them deal with managing pain associated with musculoskeletal conditions. Just like JBJS Clinical Classroom, which was developed with the NEJM Knowledge+ adaptive-learning platform, this new pain management and opioid module delivers each case-based question and then uses an algorithm that identifies individual learners’ knowledge gaps, followed by targeted content that addresses those gaps after each question has been answered.
OrthoBuzz has previously reported on studies examining the narcotic-prescribing patterns of foot and ankle surgeons. New findings published by Finney et al. in the April 17, 2019 issue of The Journal of Bone & Joint Surgery strongly suggest that the single most powerful and modifiable risk factor for persistent opioid use after bunion surgery was the opioid dose perioperatively prescribed by the surgeon.
The authors analyzed a US private-insurance database to identify >36,500 opioid-naïve patients (mean age, 49 years; 88% female) who underwent one of three surgical bunion treatments. Among those patients, the rate of new persistent opioid use (defined as filling an opioid prescription between 91 and 180 days after the surgery) was 6.2%, or >2,200 individuals. The authors found that patients who underwent a first metatarsal-cuneiform arthrodesis were more likely to have new persistent opioid use, compared with those who received a distal metatarsal osteotomy, which was the most common procedure performed in this cohort. Additional findings included the following:
- Patients who filled an opioid prescription prior to surgery were more likely to continue to use opioids beyond 90 days after surgery.
- Patients who resided in regions outside the Northeastern US demonstrated significantly higher rates of new persistent opioid use.
- The presence of medical comorbidities, preexisting mental health diagnoses, and substance-use disorders were associated with significantly higher new persistent opioid use.
However, physician prescribing patterns had the biggest influence on new persistent opioid use. A total prescribed perioperative opioid dose of >337.5 mg (equivalent to approximately 45 tablets of 5-mg oxycodone) was the major modifiable risk factor for persistent opioid use in this cohort. The authors also pointed out that 45 tablets of 5-mg oxycodone “is a relatively low amount when compared with common orthopaedic prescribing patterns” (see related JBJS study).
As orthopaedic surgeons in all subspecialties rethink their narcotic-analgesic prescribing habits, they should remember that regional anesthesia and non-opiate oral pain-management protocols have had a positive impact on pain management while minimizing narcotic use. The smallest dose of opioids for the shortest period of time seems to be a good rule of thumb.
Sometimes, patients with painful knee osteoarthritis do not get sufficient pain relief with conservative treatments and do not want (or are not suitable candidates for) arthroplasty. Now, with the advent of genicular nerve radiofrequency ablation (GNRFA), such patients have another option.
As described in a recent issue of JBJS Essential Surgical Techniques, GNRFA has been shown to provide consistent pain relief for 3 to 6 months. Using heat generated from electricity delivered via fluoroscopically guided needle electrodes, the procedure denatures the proteins in the 3 genicular nerves responsible for transmitting knee pain. Although there is a paucity of high-quality studies on the efficacy of this procedure, one study found that, on average, GNRFA led to improvement of >60% from baseline knee pain for at least 6 months.
In the authors’ practice, GNFRA is generally not repeated if it is ineffective the first time, but the procedure has been shown to be safe when administered repeatedly in patients who respond well. Proper positioning of the electrodes is essential, but the authors caution that without ample experience, “it may be difficult to isolate the exact anatomic location of ≥1 of the genicular nerves.”
General anesthesia is not required for the procedure, which is commonly performed by interventional pain specialists. Despite theoretical concerns, no Charcot-type joints have been reported after GNRFA. The authors emphasize, however, that the procedure provides temporary relief at best; it does not eliminate the potential for nerve regrowth and does not alter the arthritic disease process. Even more importantly, GNRFA needs to be studied with higher-level clinical research designs, ideally an adequately powered sham/placebo-controlled randomized trial.
For more information about JBJS Essential Surgical Techniques, watch this video featuring JBJS Editor-in-Chief Dr. Marc Swiontkowski.
The anticipation of postoperative pain associated with a large operation such as a total knee arthroplasty (TKA) scares many patients. Some worry to the point of “catastrophizing” pain prior to surgery. As orthopaedic surgeons, we try to assuage our patients’ fears through preoperative education and multimodal pain-management modalities after surgery, but there are still some patients in whom the fear of pain—and the pain itself that inevitably accompanies arthroplasty— negatively affect their outcome. Preparing such patients for surgery and helping them recover afterward despite this high anxiety are big challenges for the orthopaedic care team. Some data suggest that cognitive behavioral therapy (CBT) might help.
However, a multisite randomized trial by Riddle et al. published in the February 6, 2019 issue of JBJS did not find any differences in pain or function among patients with moderate to high preoperative pain catastrophizing scores who underwent a form of CBT focused on pain coping skills, when their outcomes were compared to those of similar patients in “usual care” or “arthritis education” arms of the study. Each group had similar WOMAC pain scores and pain catastrophizing scores to start, and all patients were found to have significant but very similar decreases in their pain scores at 2, 6, and 12 months postoperatively. Independent assessors determined that the quality of the intervention in the coping-skills and arthritis-education arms was high, suggesting that it was not poor-quality interventions that accounted for the consistent similarities among the 3 groups.
While there are many physiological and psychological factors contributing to an individual’s experience of pain, the results of this study ran surprisingly counter to prior evidence. The authors speculate that differences between the 3 groups may have been masked by the fact that all patients had such a large decrease in pain after the TKA. While that would appear to be good news, we know that there is a stubbornly large subset of patients (cited in this article as 20%) who undergo a technically and radiographically ”successful” knee arthroplasty only to have continued pain without an obvious cause. (See related OrthoBuzz Editor’s Choice post.)
These findings lead me to believe a statement that probably cannot be proven: there are some patients who will experience function-limiting pain no matter what surgery is performed, no matter which drugs are administered, and no matter what rehabilitative therapy is provided. Learning how to identify those patients and clearly communicating expectations to them pre- and postoperatively might help improve their satisfaction with their procedure.
Chad A. Krueger, MD
JBJS Deputy Editor for Social Media
This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
Orthopaedic surgeons may not be at the forefront of dealing with nonoperative nerve pain, but many of our patients who are not candidates for surgery suffer from spine-related nerve pain in their limbs, such as sciatica. Both gabapentin (GBP, Neurontin) and pregabalin (PGB, Lyrica) are used to treat chronic sciatica (CS).
Gamma-aminobutyric acid (GABA) is an important pain-related neurotransmitter, although neither GBP nor PGB affect the GABA receptor. Instead, both drugs associate with the ligand of the auxiliary α2δ-1 and α2δ-2 subunits of certain voltage-dependent calcium channels in nerves. Among other uses, Neurontin is prescribed to treat diabetic peripheral neuropathy, and Lyrica is commonly used to treat fibromyalgia.
Investigators reporting in JAMA Neurology sought to help guide practitioners in the initial choice of drug. Eighteen patients with MRIs corroborating single-sided nerve-root sciatic pain of at least 3 months duration were evaluated in an interim analysis as part of a randomized, double-blind, double-dummy crossover trial of PGB vs GBP (8 weeks of exposure to each drug with a 1-week washout in between). The primary outcome was pain intensity measured with a 10-point visual analog scale (VAS) at baseline and 8 weeks. Secondary outcomes included disability as measured with the Oswestry Disability Index and the severity and frequency of adverse events.
Relative to baseline, both drugs showed significant VAS pain reductions and disability-score improvements, However, head-to-head, GBP showed superior VAS pain reduction (mean [SD], GBP: 1.72 [1.17] vs PGB: 0.94 [1.09]; P = 0.035), regardless of the order in which it was given. There were no between-drug differences in disability scores, but adverse events for PGB were more frequent (PGB, 31 [81%] vs GBP, 7 [19%]; P = 0.002), especially when PGB was taken first.
The authors conclude that GBP was superior with fewer and less severe adverse events, and they suggest that gabapentin should be commenced before PGB to permit optimal crossover of medicines.
Robertson K, Marshman LAG, Plummer D, Downs E. Effect of Gabapentin vs Pregabalin on Pain Intensity in Adults WIth Chronic Sciatica: A Randomized Clinical Trial. JAMA Neurol. 2018 Oct 15. doi: 10.1001/jamaneurol.2018.3077. [Epub ahead of print] PMID: 30326006