Nasal Cavity Cooling for the Symptomatic Relief of Migraine Headache - A Randomized, Double Blind, Placebo Controlled Study" , the BrainCool-Migraine Study

Mechanical techniques to alleviate migraine symptoms have been used for many years, cooling and compression being the most frequently applied. Cryotherapy is the most common non-pharmacological self-administered pain-relieving method currently used by migraine sufferers. The first manuscript documenting the application of ice mixtures was published by James Arnott in 1849. Simple techniques based on cryotherapy, using various methods of cold and ice application have been reported over the last three decades. Friedman described a device using hollow metal tubes cooled by circulating cold water, applied to the periapical area of the maxillary molars. Sprouse-Blum reported benefit from applying frozen icepacks targeting carotid arteries at the front of the neck in migraine treatment.

Several pathophysiological mechanisms of action have been proposed. These mechanisms include:

1. Neurovascular mechanism: Application of cold induces vasoconstriction with subsequent decreased downstream blood flow. This leads to inhibition of the release of inflammatory mediators which results in decreased vascular permeability and local oedema.
2. Pain gating by differential effect on nerve conduction: Cryotherapy induces analgesia by slowing nerve conduction velocity, with small myelinated fibers being affected first, followed by large myelinated fibers and the unmyelinated fibers being affected last. Via mechanism of the gate control of pain, affecting the small myelinated nociceptive pain afferents first, cryotherapy induces analgesia.
3. Metabolic mechanism: Cryotherapy decreases metabolic and enzymatic activity, due to reduced demand for adenosine triphosphate (ATP) and oxygen.
4. Transient Receptor Potential (TRP) channels: Recent studies suggest that TRP channels may have a role in headache and pain genesis due to their response to environmental stimuli such as temperature changes.

The nasal cavity provides a large diffuse surface area that is highly vascular. Cooling via the nasal cavity therefore offers the ability to cool across the thin cribriform plate via both direct conductive mechanisms that do not rely on spontaneous circulation as well as indirect haematogenous mechanisms. Numerous subarachnoid and pial arterial branches exposed to the cerebrospinal fluid (CSF) have diameters in the range of the vessels of the retia mirabilia of animals in which selective brain cooling has been clearly established experimentally. Vascular anatomy allows transfer of venous blood from the skin of the head as well as nasal and paranasal mucous membranes to the dura mater thereby providing an excellent basis for the convective process of intranasal evaporative cooling. The dura mater, with its high vascularization, may transmit temperature changes to the CSF compartment, which may influence the temperature of brain parenchyma directly or indirectly, via brain arteries.

We suppose that another effect of intranasal cooling may be local vasoconstriction and subsequent associated vasoconstriction of cerebral arteries due to the presence of the nebulized coolant in the nasal cavity.