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How can patients and clinicians effectively manage diabetic neuropathic pain in 2024? At the French Diabetes Society congress, three experts provided a comprehensive overview of the treatment for these pains, the prevalence of which is increasing worldwide. A salient point was what they deemed the insufficient use of spinal cord stimulation.

Managing diabetic neuropathic pain begins with better diabetes control. But clinicians should take care not to mislead patients, said Agnès Hartemann, MD, PhD, head of the diabetology department at Pitié-Salpêtrière Hospital in Paris, France. "Managing diabetes will not have any consequences for the perceived pain," she said. In addition, there is a risk for "insulin neuritis," a rapid diabetes equilibrium usually described under insulin treatment. This condition can occur with strict diets, glucagon-like peptide 1 analogs, and semi-closed–loop systems. Rapid glycemic reduction can lead to diffuse hyperexcitability and dysfunction of small fibers and the autonomic nervous system.

Confronting Hyperexcitability

Diabetic neuropathy (DN) treatments like alpha-lipoic acid are not reimbursed in France, making access difficult. They are commonly prescribed in countries such as Italy. Nonetheless, "given their minimal effect on pain, they do not replace symptomatic treatment," said Nadine Attal, MD, PhD, neurologist at the Pain Study and Treatment Center of Ambroise-Paré Hospital in Boulogne-Billancourt, France. Therefore, there is often a shift toward purely symptomatic multimodal treatments that incorporate not only pharmacologic but also psychological means and consider patient phenotypes.

Regarding pharmacologic treatments, conventional analgesics (such as aspirin, nonsteroidal anti-inflammatory drugs, paracetamol, and weak opioids such as codeine, lamaline, and opium powder) prove ineffective because DN does not involve classical pain mechanisms like ectopic discharges.

Common and established central-acting treatments include antidepressants (duloxetine, a serotonin [5-hydroxytryptamine] and norepinephrine reuptake inhibitor, approved for DN) and certain antiepileptics like pregabalin, amitriptyline, clomipramine, and gabapentin. Clomipramine has been approved for DN, with central rather than peripheral action, no effect on small fibers or excitability. Gabapentin has been approved for peripheral DN.

"Opioids should never be prescribed as first- or second-line treatment," said Attal. Tramadol is a potential exception, but it requires discussion with specialists. In addition, "therapeutic combinations can be very interesting," she added, especially the combination of gabapentinoids and antidepressants at moderate dosages. This combination can be as effective as increasing doses in monotherapy.

Topical Treatments

Topical treatments are particularly useful for focal DN. Highly concentrated capsaicin patches (8%) are approved for peripheral DN. Application in outpatient settings provides relief for about 3 months. Capsaicin acts on small fibers, especially sensitized C-fibers. "It puts them to rest for about 3 months, thus reducing painful sensation," said Attal. Moreover, due to its effect on damaged C-fibers, it potentially has a "disease-modifying" effect, as seen in post-chemotherapy neuropathy where the painful area decreases with each application.

Another prescribed analgesic patch, 5% lidocaine, is not approved for this indication but shows effectiveness despite significant placebo effect when pain is distal and localized.

Lastly, botulinum toxin, apart from its muscle effect, has an analgesic effect. "We have shown that subcutaneous injection into the painful area can provide relief for DN, especially diabetic neuropathy," said Attal. At this stage, off-label injections are performed in pain management centers.

Neuromodulation

Pharmacologic treatments can be combined with techniques such as noninvasive neurostimulation, including transcutaneous electrical nerve stimulation (TENS) or transcranial direct current stimulation. While TENS is an older technique reimbursed with a prescription from a pain management center, an emerging cerebral neurostimulation technique in DN, which has long been known in psychiatry, include repetitive transcranial magnetic stimulation. Ambroise-Paré's pain center tested this technique on the motor cortex and found beneficial effects for at least 6 months in DN, as well as excellent tolerance. Several meta-analyses have been published on the treatment of DN. Good responses are observed in one out of two to one out of four cases.

The therapeutic algorithm of the International Association for the Study of Pain dates to 2015. It is under revision, and the updated version is expected by early 2025. The new algorithm will include neuromodulation techniques. Diabetology recommendations will emphasize therapeutic combinations. The 2020 recommendations from the French Society for the Study and Treatment of Pain distinguished between extended and localized pains. The risks associated with pregabalin have somewhat excluded it from first-line therapy.

But because a significant number of patients do not respond to pharmacotherapy, research must continue, according to the experts. For example, oxcarbazepine has shown a predominant effect in patients with DN and burning and paroxysmal pain. The goal now is to individualize management based on phenotype. New drugs are in development, including some sodium channel blockers. One molecule recently was abandoned despite promising studies. Regarding cannabis, data suggest a considerable placebo effect and moderate to negligible efficacy in meta-analyses of contradictory studies.

Spinal Cord Stimulation

Chronic electrical stimulation of dorsal columns via a posterior epidural electrode is used to strengthen pain-inhibitory physiological controls. This reversible neuromodulation technique is a symptomatic treatment for severe neuropathic pains. It induces perceptible paresthesia in the painful area. Newer modes than tonic stimulation often eliminate paresthesia.

"In France, 1600-2000 procedures are performed annually (44 centers in France)," said Denys Fontaine, MD, PhD, professor of neurosurgery at Nice University Hospital in Nice, France. "The technique has been known for 50 years, has recently undergone technological improvements and miniaturization (the stimulator has been autonomous for 3-4 years), and is without any serious complications. In the literature, the rate of infections is 2%."

"Diabetic polyneuropathy [DPN] pains fit perfectly into the indications for spinal cord stimulation, as a third-line treatment, very rarely used in France for this purpose," Fontaine added.

Yet threerandomized controlled trials suggest major efficacy in DPN, with 60% of patients experiencing more than 50% improvement, persisting long-term. Improved aspects include intensity of daytime and nighttime pains, functional and emotional impact, and quality of life.

"But we lack real-world data, and technical questions remain (such as those about sites and stimulation modalities and patient selection). Potentially, 30,000-60,000 diabetic people in France could benefit from it compared with less than 20 who undergo operation annually. This gap is mainly due to the unfamiliarity with the technique among diabetologists and those managing DN, the high burden on pain management centers, and the fact that specialized surgeons ultimately do not see diabetic patients. In 2024, too few patients are treated with spinal cord stimulation, which could potentially bring them significant relief," said Fontaine.

Hartemann had no relevant financial relationships to disclose. Attal disclosed relationships with Novartis, Grünenthal, Merz, Biogen, and Viatris. Fontaine has been a consultant for Medtronic, St. Jude-Abbott, Autonomic Technologies, Renishaw, Axonic, Boston Scientific, and Novartis and received research grants from Medtronic and St. Jude-Abbott.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.