Transnasal cooling a promising drug-free approach to tackling acute migraine attacks

An investigational neuromodulation device that delivers a controlled flow of dry, room-temperature air through the nasal passage helps relieve migraine pain, as shown in a study.

Named Mi-Helper, the tabletop device takes in ambient air, dries it with an internal desiccant, and then channels it through a single-use tubeset. Patients self-administer the air flow through the nostrils using a handpiece attached to the end of the tubeset.

The flow of dehumidified air extracts energy and induces local cooling of the nasal passage, which modulate the sphenopalatine ganglion (SPG), explained lead researcher Dr Maryann Mays from the Cleveland Clinic in Cleveland, Ohio, US.

“SPG is a nerve bundle in the back of the upper airway that is closely linked to the trigeminal nerve and is implicated in the symptomatology of migraine attacks,” Mays added.

In a randomized, double-blinded, dose-finding, sham-controlled, decentralized trial, transnasal evaporative air flow at 10 L/min vs sham was associated with significantly greater frequency of achieving freedom from pain at 2 hours post-treatment compared with sham (47.1 percent vs 16.0 percent; p=0.029). [Mays M, et al, AAN 2025]

Likewise, more patients who underwent treatment with transnasal evaporative air flow at 10 L/min vs sham achieved pain relief at 2 hours (70.6 percent vs 56.0 percent), although the difference did not reach statistical significance (p=0.339), Mays noted.

Result for sustained pain freedom without rescue medication was also in favour of transnasal evaporative air flow at 10 L/min vs sham (41.2 percent vs 16 percent), but the p-value was slightly above the conventional threshold for significance (p=0.069).

Mays pointed out none of the nine patients who achieved freedom from pain at 2 hours with 10 L/min transnasal evaporative air flow took rescue medications within 24 hours, and only one had recurrence of mild headache pain.

In terms of tolerability, none of the patients discontinued treatment due to discomfort with device use. The overall incidence of device-related adverse events was low, even though it was highest among patients in the 10 L/min-dose group, according to Mays.

“Most common side effects were rhinorrhoea, nasal irritation, ear pressure, and congestion. Importantly, all side effects were mild or moderate and self-limited, with only one patient [in the 10 L/min-dose group] requiring over-the-counter medication,” she continued. “There were no serious adverse events.”

The findings point to the potential of Mi-Helper as a noninvasive, drug-free alternative for acute migraine treatment, Mays said. “The treatment is short and provides a quick, acting, and durable effect.”

The SPG has long been recognized as a promising target for migraine treatment, according to Mays. In line with this, three earlier studies on acute migraine were conducted in headache clinics using a prototype of the transnasal cooling device. The present study was aimed at establishing the most effective dose for the Mi-Helper device, while evaluating its safety and tolerability for the acute treatment of migraine with or without aura in an in-home setting.

A total of 172 adult patients who met the criteria for episodic migraine were enrolled and randomized to treatment with the Mi-Helper device at an air flow of 4 (n=14), 6 (n=18), or 10 L/min (n=17) or sham (n=25). Treatment was self-administered for 15 min during an acute attack.

The mean age of the patients ranged between 38 and 44 years across groups, more than three-fourths overall were women, and most were White. The best active dose was 10 L/min.

Mays shared that recruitment for a decentralized, pivotal trial of the Mi-Helper commenced at the end of March 2025. The results are anticipated to be available by November.