Cite as: Rasouli M, Narouze S, Shanthanna H. Opioid analgesia for acute low back pain and neck pain: putting the OPAL trial findings in the right context and perspective. ASRA Pain Medicine News 2024;49. https://doi.org/10.52211/asra080124.007.

Neck and low back pain are very common in adults. It is estimated that 84% and 50% of individuals experience clinically significant back and neck pain, respectively, during their lifetimes.^1,2 Neck and low back pain are considered major causes of disability³ and are considered a significant burden to society and the health care system.⁴ Interestingly, social factors and culturally constructed illness behaviour could influence the transition from acute pain to chronic pain, as has been observed in whiplash injury patients with country-specific differences, despite similar rates of vehicular collisions.⁵ Acute neck and low back pain are usually self-limiting, and improvement is expected within 1 to 2 months in the majority of patients.^2,4 Based on the American College of Physicians guidelines, nonpharmacologic therapy, and non-opioid pharmacotherapy are considered as the first line of treatment.⁶ Opioids are not usually recommended as the initial treatment for acute neck and low back pain^6,7. However^, there is a paucity of literature regarding the use of opioids for the treatment of acute neck and back pain. Given this background, we review the recently published opioid analgesia for acute low back pain and neck pain (OPAL trial),⁸ discuss methodological considerations and limitations that need to be considered for future trials, and highlight key messages for clinical practice.

The OPAL trial was designed and conducted to address the gap in the available literature regarding the use of opioids in treating acute axial neck and low back pain in patients with or without radiation to their arms or legs, respectively.⁸ This triple-blinded, randomized, placebo-controlled trial (RCT) was performed in 157 primary care clinics and emergency departments in Sydney, Australia. The study was conducted over 6 years, from February 2016 to March 2022, recruiting 347 patients. The trial aimed to assess the safety and efficacy of short-term (maximum 6 weeks) opioid therapy for the treatment of acute axial neck and low back pain. Pain severity at 6 weeks after randomization was considered as the primary outcome. Multiple secondary outcomes, including but not limited to physical functioning, quality of life, work absenteeism, and adverse effects, were evaluated. Patients in the opioid group received “modified release” oxycodone-naloxone (5 mg-2.5 mg) twice a day that was titrated up to the maximum dose of 10 mg oxycodone twice a day if needed. The study did not find a significant difference between the opioid and placebo groups for pain scores at 6 and 12 weeks. There was no difference between the groups in terms of physical functioning endpoints. More patients in the opioid group had ongoing pain at 26 and 52 weeks; however, it was not statistically significant. The number of reported adverse effects was similar between the two groups. The findings of the OPAL trial seem to be consistent with a previous RCT conducted by Friedman and colleagues.⁹

It is important to consider the challenges and methodological limitations of the OPAL trial. It took 6 years to finish recruitment from 157 centers. The exclusion criteria were modified to facilitate recruitment. A modified-release opioid (long-acting oxycodone) was used for the intervention. However, long-acting opioids are not recommended for the treatment of acute pain, including acute low back or neck pain with or without radicular symptoms, particularly in opioid naïve patients.¹⁰ A more reasonable approach would have been a prescription of as-needed immediate-release weak opioids.

Implementing a standardized treatment protocol and compliance with treatment is critical for evaluating the effect of the study intervention. In the OPAL trial, apart from study interventions, the study doctor was asked to provide guideline-recommended treatment to both groups without controlling which care guidelines were followed and without collecting data on which treatments were used. In the face of recruitment challenges, the study investigators were more liberal with the treatment protocol. The variability of care implementation makes the fidelity of study interventions uncertain. Nearly the same rate (56% versus 58%) used concomitant medications in both the opioid and non-opioid groups. In addition, only half were compliant with study interventions; among 58% of the participants reporting compliance, only 50% were compliant with treatment, defined as taking equal or greater than 80% of prescribed medications. These factors, when combined with the fact that nearly 70% of acute low back pain patients self-recover within 6 weeks,¹¹ could make the study population non-responsive to any potential therapy (including opioids). In general, strong analgesics, such as opioids, are recommended for the treatment of moderate to severe acute pain, and continuing opioids for the treatment of mild pain (as followed in the study with an attempt to have 0 or 1 level pain) is not justified or recommended. All these factors could have contributed to the non-compliance and a higher rate (overall 25%) of dropout in both groups.

Implementing a standardized treatment protocol and compliance with treatment is critical for evaluating the effect of the study intervention.

Despite these limitations and concerns, the OPAL trial makes an important contribution to the current literature regarding the use of opioids for the treatment of acute neck and low back pain.

As highlighted by the OPAL investigators, it's true that there is paucity of literature evaluating the benefits of opioids in acute neck and low back pain, including when acute musculoskeletal pain conditions are considered.¹² However, study findings might not be applicable to the United States with a different health care system and recent changes to opioid prescribing. In a 2019 database study of opioid prescriptions for acute and chronic pain management among Medicaid beneficiaries (5,051,288 patients), prescriptions of opioids for low back pain accounted for only 14% of prescriptions, with orthopedic indications being the most common reason (34.8%) followed by patients having a dental diagnosis (17.3%).¹³ This is a much lower figure compared to the 2019 Australian study in which two-thirds (69%) of back pain patients in the emergency room were prescribed opioids as the first line of treatment.¹⁴ In fact, between 2009 and 2018, opioid prescriptions decreased by 66.3% among emergency departments in the United States, with a greater relative reduction in musculoskeletal pain as compared to kidney stones or fractures.¹⁵ Patients are more likely to receive multimodal analgesia when presenting to primary care and emergency medicine physicians than opioid therapy, particularly long-acting opioids.¹⁰

In conclusion, opioids are not recommended for the treatment of acute non-specific neck and back pain, as supported by the OPAL study findings. However, there may be some patients with moderate-to-severe pain refractory who might benefit from a short-term, low-dose opioid prescription. When opioids are prescribed for acute pain, they should be at the lowest effective dose, in a short-acting form, to be taken as needed, and for a short duration appropriate to the expected recovery.¹⁰ With all opioid prescriptions, it is important that the prescribing physician includes an assessment of treatment goals, benefits, and risks. Given the considerations discussed above, it is unlikely that future placebo-controlled trials looking at opioid use with similar designs would add much to the given evidence. To address the variability in treatment response based on genetic and phenotypic characteristics, researchers should consider adaptive trial designs, such as an enrichment trial^16, where patients who might benefit are selected either by clinical response or biomarkers, which would be more meaningful and clinically relevant. At the same time, it is important to take measures to ensure treatment compliance and follow-up so that the potential for bias is minimized and the internal validity of the trial is not compromised. The OPAL trial and existing literature support the existing guidelines and recommendations for clinicians to maximize the use of non-pharmacological interventions and, if necessary, preferentially use acetaminophen and NSAIDs for the management of acute low back and neck pain.

References

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