New Randomized Trial: Don’t Use Opioids for Acute Nonspecific Low-Back or Neck Pain

Sudden low-back and neck pain are frequent causes of substantial discomfort and dysfunction. Although opioid analgesics are commonly used to treat such pain, there is little evidence they are effective.

A recent clinical trial, conducted in Australia and published in The Lancet in July 2023, adds to the evidence from prior research that opioids are no better than placebo and some nonprescription medicines (such as ibuprofen) for acute nonspecific musculoskeletal pain.[1],[2],[3]

Background on acute low-back and neck pain

Low-back pain is the leading cause of disability in the United States, and neck pain is the sixth leading cause.[4] In a given three-month period, and generally increasing with age, low-back pain occurs in 28-46% of adults age 18-64 years.[5] The problem usually resolves within four to six weeks, though 5-10% of cases may last longer.[6] The goal of treatment, when needed, is short-term relief from pain and dysfunction.[7] For neck pain, degenerative changes (age-related wear and tear that, for example, can lead to pinched nerves) are more common than muscle or ligament strains, but similar treatment principles otherwise apply.[8]

Non-pharmacologic approaches to treatment include posture and sleep-position modifications, in-home exercises, superficial heat, massage, acupuncture and spinal manipulation. Treatment with nonsteroidal anti-inflammatory drugs also may be helpful. When such approaches fail to limit symptoms within a few weeks, cognitive behavioral therapy, physical therapy, muscle relaxants or drugs other than opioids sometimes are used.

Despite guidelines recommending that opioids be used rarely for acute low-back or neck pain (such as when other treatments have not worked, and then for only for a maximum of three days),[9],[10] in Australia up to two-thirds of people receive an opioid as an initial treatment. In the United States, as of 2020, opioid prescriptions were down from previous years but still at a high rate of 43 prescriptions per 100 people.[11]

The new randomized placebo-controlled trial[12]

In the randomized placebo-controlled trial, opioids for low-back and neck pain were compared with placebo. Subjects were recruited from 157 primary-care or emergency departments in Sydney, Australia, and 347 subjects with 12 or fewer weeks of moderate-to-severe low-back or neck pain were enrolled. The subjects were randomized to receive either an oral opioid (174) or placebo (173) to treat their pain. The opioid analgesic selected was oxycodone (OXYCONTIN, ROXICODONE, ROXYBOND, XTAMPZA ER and generics). In Australia, oxycodone is the most commonly prescribed drug for acute back pain.

Oral oxycodone (up to 10 milligrams [mg] twice per day) was combined into a single tablet with the opioid antagonist naloxone (nasal sprays: KLOXXADO, NARCAN, RIVIVE and generics, up to 5 mg twice per day). The researchers’ goal was to create a formulation that minimized the common opioid adverse effect of constipation and to reduce the likelihood that the development of constipation might have allowed the research subjects to guess their treatment. Although naloxone can reverse or eliminate the bioactivity of opioids, naloxone’s effects were attenuated in the formulation used in the trial because the bioavailability of oral naloxone is only 3%, compared with 60-70% for oxycodone.

The trial was triple-blinded, meaning that the subjects, clinicians and dispensing pharmacists all did not know which treatment arm each subject was assigned to. In addition to instruction in the monitoring of the medication and placebo doses, all participating doctors were trained to provide guideline-recommended care that included reassurance of a positive prognosis, encouragement towards activity (rather than bed rest) and non-opioid analgesics as needed.

Of the subjects, 51% were male and 49% were female. Their mean age was 45 years; 80% had low-back pain exclusively, and the mean pain duration was 18 days. Almost all (97%) of the subjects were referred to the study from primary care. On a 10-point pain-severity scale, where 0 is the absence of pain and 10 is the worst pain imaginable, the mean pain score at the beginning of the study was 6. The primary outcome was pain severity as measured with the same scale and assessed six weeks after medication dosing began. Patients continued their opioid or placebo treatment for a maximum of six weeks (or less if their pain score declined to 0 or 1 for at least three consecutive days).

After excluding subjects who had dropped out of the trial by week six, 151 subjects in the opioid group and 159 subjects in the placebo group were included in the primary analysis. The mean pain score at six weeks was 2.8 in the opioid group and 2.3 in the placebo group, a 0.5-point difference that was not statistically significant. By week 52, there was a small (0.6 point) but significant difference in pain severity favoring the placebo group. At weeks six and 12, quality-of-life scores for “physical functioning” were equivalent between the groups; for “mental health,” the quality-of-life scores were slightly better in the placebo group.

There was no difference between groups in the proportion of patients reporting adverse events. Although the risk of misuse was similar between groups at weeks 12 and 26, it was significantly higher in the opioid group at week 52 (20% of the subjects in the opioid group who were assessed at 52 weeks, as compared with 10% of those assessed in the placebo group). Subjects in the opioid group reported nausea and vomiting, constipation, dizziness and drowsiness more frequently. Nonetheless, the trial showed no treatment-group imbalances for the number of subjects who were compliant with their assigned drug regimen or who were able to guess their group assignment before the trial was unblinded.

What You Can Do

The new study of opioid analgesia for nonspecific acute low-back and neck pain is a rigorous and well-conducted clinical trial that adds to the evidence from prior trials that opioids are ineffective and should not be used for these indications. When treatment is needed for these common ailments, consider non-pharmacologic approaches and nonsteroidal anti-inflammatory drugs unless there are reasons not to use these medications.

Remember that acute low-back and neck pain are usually self-limiting and often resolve within four to six weeks if not sooner, with or without treatment. If your pain is unbearable or does not begin to resolve in a few weeks, consult with a doctor for additional diagnostic and treatment options.
 

References

[1] Scott G, Gong J, Kirkpatrick C, Jones P. Systematic review and meta-analysis of oral paracetamol versus combination oral analgesics for acute musculoskeletal injuries. Emerg Med Australas. 2021;33(1):107-113.

[2] Busse JW, Sadeghirad B, Oparin Y, et al. Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries : A Systematic Review and Network Meta-analysis of Randomized Trials. Ann Intern Med. 2020;173(9):730-738.

[3] Friedman BW, Dym AA, Davitt M, et al. Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial. JAMA. 2015;314(15):1572-80.

[4] Damm H, Jönsson A, Rosengren BE, et al. Prevalence and morbidity of neck pain: a cross-sectional study of 3000 elderly men. J Orthop Surg Res. 2023;18(1):36.

[5] Lucas JW, Connor EM, Bose J. Back, lower limb, and upper limb pain among U.S. adults, 2019. NCHS Data Brief. 2021 Jul;(415):1-8.

[6] Shokri P, Zahmatyar M, Falah Tafti M, et al. Non-spinal low back pain: global epidemiology, trends, and risk factors. Health Sci Rep. 2023;6(9):e1533.

[7] Knight CL, Deyo RA, Staiger TO, Wipf JE. Treatment of acute low back pain. UpToDate. December 2023.

[8] Isaac Z. Management of nonradicular neck pain in adults. UpToDate. December 2023.

[9] Knight CL, Deyo RA, Staiger TO, Wipf JE. Treatment of acute low back pain. UpToDate. December 2023.

[10] Isaac Z. Management of nonradicular neck pain in adults. UpToDate. December 2023.

[11] Jones CMP, Day RO, Koes BW, et al. OPAL Investigators Coordinators. Opioid analgesia for acute low back pain and neck pain (the OPAL trial): a randomised placebo-controlled trial. Lancet. 2023 Jul 22;402(10398):304-312.

[12] Ibid.