Drug-Free Noninvasive Thermal Nerve Block: Validation of Sham Devices.

Headache is a leading cause of disability and suffering. One major challenge in developing device treatments is demonstrating their efficacy given devices' often-high placebo rate. This paper reviews the importance of validating sham devices as part of finalizing the design for larger-scale prospective randomized controlled trials in patients with chronic headache as well as the results of a prospective, single-blind trial to validate two potential sham noninvasive thermal nerve block devices. Study participants were trained to self-administer thermal nerve block treatment using sham devices in an office visit. Two different sham systems with different temperature profiles were assessed. Devices were offered for patients to use daily at-home for one week to assess the durability of sham placebo effects before participants were given active treatment in a second office visit followed by another optional week of self-administered active treatment at-home use. Sham treatments reduced pain scores by an average of 31% from 6.0 ± 2.3 to 4.3 ± 3.3, including two participants who fell asleep during the in-office treatment and woke up with no pain, but whose pain recurred after returning home during at-home use of the sham system. In-office active treatments reduced pain scores by 52% from 6.7 ± 2.1 to 3.3 ± 2.9 with sustained pain relief during optional at-home use. Successful blinding for the study was confirmed with an ideal Bang's Blinding Index of 0 and an ideal James' Blinding Index of 1. Both the sham and active treatments were viewed by participants as highly credible, and credibility increased from the beginning to end of sham treatments on average.

Temperature-Mediated Nerve Blocks in the Treatment of Pain.

PURPOSE OF REVIEW: Analgesic hot and cold temperatures have been used for both conservative and ablative therapies for millennia. There are well-known locoregional neurovascular changes associated with the application of heat or ice in the literature and in practice. The oscillation between heat and cold has recently been identified as a synergistic mechanism of action with early translational results in humans. RECENT FINDINGS: Recent mechanistic work in the feline model has demonstrated that a reliable, reversible nerve block can be achieved within a temperature range that is non-destructive (15-45°C). The underlying mechanism is a newly described hysteresis in the responsiveness of peripheral nerves to alternating thermal stimuli resulting in nerve blockade. Recently presented feasibility data reports positive results in subjects with occipital pain and peripheral scar pain in terms of pain and associated symptom improvement. Temperature-mediated changes in pain and sensation have been observed for hot and cold applications at a variety of temperatures. Recent insights into the synergy between preheating followed by cooling resulting in peripheral nerve fiber block has potential in a variety of conditions in which peripheral nerve etiology is noted. Recent findings in chronic headache patients report decreased pain and symptom improvement. Further studies are ongoing to understand the indications for this novel therapy.