It has been recently noticed that dust originating from deserts can be transported to other continents by the atmosphere and has an adverse effect on public health, such as increased asthma attacks. Dust originating from the Saharan Desert could initiate a series of reactions upon contact with cloud water and results in the formation of reduced iron (Fe2+), oxalate and various basic amino acids. We aimed to evaluate whether the simulation of Saharan dust-containing atmospheric conditions could trigger the trigeminovascular system. Freely moving rats incubated within simulated atmospheric conditions containing (i) Saharan dust, (ii) Co-60 gamma ray-treated Saharan dust (sterilized) and (iii) dust-free air, were investigated for the presence of c-fos expression in trigeminal nucleus caudalis (TNC) and for NOx (nitrate+nitrite) levels in blood samples. Atmospheric samples were analysed for microorganisms. Saharan dust-containing atmospheric conditions induced c-fos expression in nociceptive neurons within TNC. The number of c-fos+ neurons in superficial lamina of TNC was significantly higher in the Saharan dust group (32.9 +/- 5.3, P = 0.0001) compared with dust-free air (11.02 +/- 2.7) or Co-60-treated Saharan dust groups (15.01 +/- 2.4). An increase in NOx levels was detected in blood samples of rats exposed to Saharan dust-containing atmosphere. This study has revealed an unknown environmental factor as a possible trigger for headache. It is the first time that transport of Saharan dust with the atmospheric air stream has been documented to be able to trigger the trigeminovascular system in animals. Further studies are needed to explore the mechanisms and molecules that mediate the nociceptive effect and to guide new treatment strategies.