PITTSBURGH, Pennsylvania — Transcranial direct-current stimulation (tDCS) is gaining interest as a potentially useful nonpharmacologic approach to the treatment of chronic pain, with new research from a clinical randomized trial showing significant improvements in pain associated with knee osteoarthritis in older adults.

"We chose to test this on knee osteoarthritis because that is the leading cause of pain and disability in people aged 45 and above," Brian Ahn, PhD, RN, University of Texas Health Center at Houston, Texas, told Medscape Medical News.

"We found a statistically significant mean difference between patients receiving tDCS and a sham treatment in terms of clinical pain severity," he said.

TDCS has been evaluated for applications ranging from depression to stroke rehabilitation and cognitive aging and dementia, but the new study represents the first double-blind, randomized study of tDCS in chronic pain, Dr Ahn noted.

The study, presented here at the American Pain Society (APS) 2017 Annual Scientific Meeting, involved 40 adults aged 50 to 70 years (mean age, 59 years), including 21 women, with pain from knee osteoarthritis. They were randomly assigned to receive five daily sessions of tDCS or a sham treatment for 20 minutes in each session.

Because tDCS produces a tingling sensation, the sham treatment involved 30 seconds of tDCS current at the beginning of the session and 30 seconds at the end to provide a similar sensation. The current was delivered with a code that allowed the tDCS operator to be blinded to the treatment the patient was receiving.

The treatment involved placement of the anode electrode over the primary motor cortex of the brain hemisphere that was contralateral to the affected knee, and the cathode electrode was placed over the supraorbital regions ipsilateral to the affected knee.

The results, after the five daily sessions, showed a greater reduction in knee pain on a clinical pain severity scale of 0 to 100 in the tDCS group (18.50 ± 3.60) compared with the sham group (6.45 ± 2.26), for a mean difference between the groups of 12.05 (P = .007; Cohen's d = 0.90).

"Because the study was small, it's important to see an effect size, and this was a large effect size showing the treatment was effective."

Dr Ahn speculated that the mechanism by which tDCS may address knee osteoarthritis pain could be related to its neuromodulatory effects.

"Recent evidence shows that knee osteoarthritis pain is a centralized pain, so there could be centrally modulated mechanisms," he said.

Adam J. Woods, MD, assistant director of the Center for Cognitive Aging and Memory at the University of Florida's McKnight Brain Institute, Gainesville, a coauthor on the study, underscored that the results were encouraging.

"The overall effect size was large and exciting," he said in presenting the findings at the meeting.

"Comparatively, in most medication trials, you might see effect sizes of about 0.2 or 0.3, so this is an example of why we're excited about tDCS as a treatment for pain," he said.

Dr Woods and his colleagues are evaluating tDCS in a larger, multisite study, the Augmenting Cognitive Training in Older Adults (ACT) trial, which is the first phase 3 study to evaluate the intervention for neurocognitive effects.

While pain is not a primary outcome, the study should offer important insights for pain nonetheless, he said.

"About 40% of older adults who come into these trials have chronic pain of one form or another, and it will be helpful that some in the study will and will not have pain."

"This is an ancillary add-on, so, while we're not specifically targeting pain it's an opportunity to evaluate a variety of pain types that typically affect older adults."

Some key insights that have already been determined regarding tDCS include the observation that certain medications can alter the effects of the treatment, including sodium channel blockers and glutamatergic drugs.

"Studies have shown that sodium channel blockers can completely block the excitatory effects of tDCS, and glutamatergic and GABAergic drugs are much the same, while calcium channel blockers tend to attenuate but not block the effect."

The placement of electrodes is more important than previously believed, Dr Woods added.

"In the early days of tDCS, placement did not seem to matter, but we now know that where we put the electrodes appears to matter in terms of neurophysiological as well as behavioral response."

"Moving the electrode by as little as 2 cm can change effects," he said.

Dr Woods noted that important advances are being made to potentially allow for in-home use of the tDCS, which could make a substantial difference in its feasibility for many patients.

"A person in pain may be willing to come into the clinic for 5 days a week for 2 weeks, but if they can come to the clinic and receive their equipment and then go home and use the telemedicine to use it, that could dramatically increase adherence and the ability to reach pain patients who can benefit from this."

The study was funded by the Claude D. Pepper Older American's Independence Center, the University of Texas School of Nursing at Houston, the University of Florida Center for Cognitive Aging and Memory, and the National Institute on Aging. The authors have disclosed no relevant financial relationships.

American Pain Society (APS) 2017 Annual Scientific Meeting. Abstract 456. Presented May 19, 2017.

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