<p>Usefulness of a Double-Blind Placebo-Controlled Response Test to Demonstrate Rapid Onset Analgesia with Phenytoin 10% Cream in Polyneuropathy</p>

Abstract

Purpose: Topical analgesics are an upcoming treatment option for neuropathic pain. In this observational study, we performed a double-blind placebo-controlled response test (DOBRET) in patients with polyneuropathy to determine the personalized analgesic effect of phenytoin 10% cream. Patients and Methods: In a double-blind fashion, 12 consecutive adult patients with symmetrical painful polyneuropathy and equal pain intensity of ≥4 on the 11-point numerical rating scale (NRS) applied phenytoin10% cream on one painful area and a placebo cream on the corresponding contralateral area. We defined responders as patients who experienced a pain reduction ≥2 NRS points from baseline and ≥1 NRS point difference in pain reduction in favour of phenytoin 10% cream compared with placebo cream within 30 minutes after application. We also evaluated the percentage of pain reduction and frequency of 30% and 50% pain relief from baseline. Results: Six patients (50%) were responders. Compared with placebo cream, pain reduction was higher in phenytoin 10% cream-applied areas with mean difference in pain reduction of 1.3 (95% CI: 1.1 to 1.8; p<0.001) on the NRS and mean percentage difference in pain reduction of 22% (95% CI: 13% to 32%; p =0.03). All responders had at least 30% pain reduction, and 4 out of 6 had at least 50% pain reduction in the phenytoin 10% cream applied area. All nonresponders had less than 30% pain reduction. No side effects were reported. Conclusion: A DOBRET is easy to perform, quickly identifies an analgesic effect in responders and could be a useful tool to personalize neuropathic pain treatment with topical formulations.

No Detectable Phenytoin Plasma Levels After Topical Phenytoin Cream Application in Chronic Pain: Inferences for Mechanisms of Action

“…A noticeable pain reduction was reported after a median onset of action of 22.5 minutes. This fast onset of action and no systemic side effects also correspond with earlier reports, 9,20,21 and supports a peripheral mechanism of action. In contrast, pain reduction after intake of oral phenytoin emerges approximately after 24 hours, supporting a central mechanism of action.…”

Neuropathic pain in spinal cord injury: topical analgesics as a possible treatment

“…Decrease in NP will be described during these treatments. This N-of-1 response test has been used in clinical practice to establish a personalized treatment [33,34].…”

Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain—Narrative Review

“…The long history of topical phenytoin utilization in wound healing without any signs of dermatotoxicity and its possible mechanisms of action lead to the idea of topical phenytoin application in patients with LNP. To date, observational studies on the efficacy and safety of topical phenytoin up to 30% have been performed in more than 100 patients with LNP of several etiologies including hernia pain [ 95 , 96 , 97 , 98 , 99 , 100 , 101 ]. In an observational study describing 70 neuropathic pain patients treated with phenytoin 5% and 10% creams, 70% of these patients experienced at least 50% pain relief [ 95 ].…”

“…The mean pain reduction after 30 min as measured with the 11-point numerical rating scale in the phenytoin 10% cream area was 3.3 (SD: 1.3) and in the placebo cream area 1.2 (SD: 1.1). The pain-relieving effects of phenytoin cream compared with placebo cream were confirmed by a study examining the double-blind placebo-controlled response test (DOBRET) [ 98 ]. Six out of 12 NP patients were classified as responders.…”