Pain Management
Kevin Willmann
Ten years after their last recommendations for neuropathic pain treatment, a special interest group conducted an analysis that’s findings support modest revisions to recommended treatments. The group’s recommendations were published in the May 2025 issue of The Lancet Neurology.
According to the recommendations, capsaicin cream is now considered a second-line treatment for neuropathic pain, although with a weak recommendation. Its efficacy was considered “inconclusive” a decade ago. Tramadol—considered a second-line treatment 10 years ago—has now been grouped with opioids as a third-line treatment with a weak recommendation. One other treatment, repetitive transcranial magnetic stimulation, was not evaluated in 2015 but was assessed in 2025. The group recommended this noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain as third-line treatment due to its low certainty of evidence, low availability, and high cost.
Neuropathic pain is “pain caused by a lesion or disease of the somatosensory nervous system,” according to the International Association for the Study of Pain (IASP). NIH notes that neuropathic pain results in “impaired quality of life and is often poorly managed.” The health agency estimates that 7% to 8% of adults suffer from neuropathic pain, and it can be found in a quarter of people suffering from diabetes and 35% of people with HIV.
The first guidelines for treatment of neuropathic pain were published in 2007 by the Special Interest Group on Neuropathic Pain of the IASP, with the most recent revision published in 2015.
The 2025 analysis was “a pretty work-intensive project, and it took us quite a bit of time to get it all together, so some of the difference in time is related to the amount of work that went into this iteration of the guidelines,” said Ted Price, PhD, Ashbel Smith Professor at the University of Texas in Dallas, who also serves on the special interest group.
For the 2025 analysis, the group searched PubMed, EMBASE, Clinical trials.gov, and International Clinical Trials Registry for pharmacological interventions for neuropathic pain to make its recommendations. Researchers performed a review and meta-analysis of 40,000 participants across 313 randomized controlled trials.
The group used GRADE methodology to assess the certainty of evidence provided in the results and conducted analyses to evaluate any potential biases. Other considerations used to align recommendations with patient priorities included adverse events, accessibility, cost, and engaged lived experience.
Based on their review, the group continues to recommend tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, and gabapentinoids as first-line treatments. Due to the increased risk of adverse effects in older adults, plus drug-related deaths in those taking gabapentinoids and opioids, the study authors recommend prescribers assess the risks when proposing those treatments.
Price said the new recommendation of capsaicin cream as a “second-line” treatment with a weak recommendation was due to a larger number of studies showing efficacy completed over the last 10 years. Tramadol was demoted as a third-line treatment with a weak recommendation. The key change in this recommendation “is that it is now clear that this drug has stronger opioid effects than was previously appreciated, so the abuse potential is higher,” said Price. He noted that weak recommendations “boil down to quality of evidence, number of studies, and agreement from the authors of the study.”
Price is optimistic in regard to future testing for better and more effective treatment options for those suffering from neuropathic pain.
“There is a lot of exciting work happening in the pain field now, and I think we are going to see many new treatments emerge in the next 10 years,” he said. ■