PHILADELPHIA — Blocking agents delivered to genicular nerves around the knee markedly reduced osteoarthritis patients’ perceptions of pain, far more than those receiving placebo injections, a randomized trial showed.

At week 4 following the injections, patients in the nerve block group reported mean reductions in pain scores of 3.0 points from baseline on a standard 10-point scale, compared with an average 0.2-point reduction among those assigned to placebo, reported Ernst Shanahan, BMBS, MPH, PhD, of Flinders Medical Centre in Adelaide, Australia, and colleagues.

But by week 8, the effect had clearly begun to fade, with average pain scores rising by 0.7 points from week 4 in the nerve block group. And at week 12, mean scores had increased another 0.7 points and no longer differed significantly from the placebo group.

The findings were published in Arthritis & Rheumatology and were also set to be presented Monday at the American College of Rheumatology annual meeting.

It’s the first demonstration in a randomized, placebo-controlled trial that local nerve block effectively relieves knee osteoarthritis pain.

Shanahan and colleagues conceived the trial to determine whether previous reports of success in individual cases were really credible. These were summarized in a recent review, which indicated that the approach improved function and reduced pain for up to 6 months. But these studies had no controls, a crucial limitation given that knee osteoarthritis pain is notoriously subject to the placebo effect.

For the randomized trial, Shanahan’s group enrolled 64 patients, assigned 1:1 to receive nerve blocks or placebo in a single session. Celestone chronodose and bupivacaine were the blocking agents used, injected adjacent to three nerves around the knee: the superolateral, superomedial, and inferomedial genicular nerves. These were located via ultrasound for precise placement. The placebo group received subcutaneous saline injections at the same sites on the skin surface but not penetrating to the nerves. Patients were allowed to continue taking their usual pain medications as needed.

Pain was assessed via visual analog scales. Overall osteoarthritis severity was evaluated with the Western Ontario-McMaster Universities Osteoarthritis Index (WOMAC) system, which measures pain, stiffness, and disability in separate domains and in a total score.

Mean patient age was about 70 in the nerve block group and 66 in the placebo group. Just over half of the former were women, while two-thirds were women in the placebo group. Baseline pain scores averaged 6.3 in the nerve block group and 5.5 in the placebo group.

All of the key outcome measures including WOMAC scores followed the same pattern: the nerve block group saw sharp improvements at their first post-injection evaluation, conducted at week 2, which was maintained through week 4. Scores on each then began returning to baseline levels. The placebo group, meanwhile, had little change in any measure during the study.

The latter may raise eyebrows among rheumatologists, given that placebo recipients in other intervention trials for osteoarthritis typically show major improvement, if temporary. Shanahan and colleagues offered an explanation in the journal report: “We speculate that the patients’ prior pain experiences, extending over years, the degree of severity of their structural changes (most were waiting for total knee arthroplasty), or the fact that the trial was a placebo-controlled study and not a comparator study may have diminished the placebo effect.”

Overall, though, the future looks bright for nerve block as an osteoarthritis palliative. “Many of the patients requested repeat [treatments] at the end of the study. Based on our findings, we believe it is reasonable to offer this intervention,” the researchers wrote.

The nerve blocks appeared safe as well as effective. Shanahan and colleagues said no complications were observed, either during procedures or at subsequent clinic visits.

Limitations included the small number of patients and the possibility that patients could tell which treatment they were getting (clinicians giving the injections obviously were not blinded). Also, the researchers noted that five patients were lost to follow-up, which “may have slightly affected the overall results of our study.”

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