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The bigger picture

Migraine and our sense of smell — more about an astonishing connection

 

What we smell affects how we experience pain. This connection has been known literally for thousands of years. Even the ancient Egyptians wrote about it. However, research into the precise mechanisms behind the phenomenon is fairly new. Groundbreaking discoveries in this field were made by American scientists Richard Axel and Linda Buck, who were awarded the Nobel Prize in Medicine in 2004 for their work on our sense of smell. They found out that our perception of odor is governed by specialized olfactory cells in the lining of the nasal cavity. These cells are directly linked to the olfactory bulb in the brain. Interestingly, this olfactory center is also connected to brain regions responsible for memory, emotions, and our sensitivity to pain.

 

Do odors trigger migraine attacks? If so, which ones?

For many people in the migraine community, the link between pain and specific odors is nothing new. Quite a few migraine sufferers say that specific odors trigger migraine attacks. As a result, they try to avoid smells that have triggered an attack in the past. Response to odors is highly individual. Potential triggers include the scent of a particular flower, kitchen smells, cigarette smoke, car exhaust fumes, sweet perfumes, and more. The scientific term for an aversion to certain smells is “osmophobia”. Research shows that sensitivity to specific odors is particularly common among people who experience migraines with aura. No such connection has been found in people suffering from tension-type headaches.

 

Smell-induced migraines: the statistics

The relationship between odor sensitivity and migraines was investigated in a Dresden University Hospital study in over 100 participants. The researchers looked at the intensity and frequency of sensitivity to specific smells at different stages of a migraine attack. 62% of participants (nearly two-thirds) reported heightened sensitivity to smells during the pain stage of a migraine episode. 38% experienced this sensitivity even before the pain began. Almost one-third of respondents said they were hypersensitive to odors all the time.

Approximately half of the study participants suffered from migraines with aura. Individuals with aura were twice as likely to be hypersensitive to smell as those without aura. The study’s findings suggest that a longer lifetime history of migraine and more severe migraine-associated impairment correlate with a greater disease burden and poorer quality of life due to smell sensitivity issues.

 

The link between smell and pain

Smell sensitivity and pain perception are interconnected on a neurological level, with one sensory system influencing the other. As well as affecting the sensory cells of the olfactory mucosa, smells also activate the trigeminal nerve, which innervates parts of the face and plays a crucial role in pain processing. Additionally, direct neural connections exist between olfactory cells and the trigeminal nerve. As a result, stimuli affecting the olfactory system can activate the trigeminal nerve, thereby increasing the likelihood of a migraine attack.

The close relationship between smell and pain perception is further highlighted by the fact that some people with no sense of smell are also unable to feel pain. This phenomenon is caused by a genetic mutation that means these individuals lack a specific protein encoded in their DNA, affecting both their ability to detect odors and to feel pain.

 

Can you “unlearn” how to smell?

Given the link between heightened smell sensitivity and migraines, do migraine sufferers have a particularly acute sense of smell? The opposite appears to be true. A study in this area found that people with migraine consistently had a higher odor detection threshold (“olfactory threshold”) than individuals without migraines. In other words, they only detected smells when exposed to higher concentrations. This was especially true for individuals with aura.

Earlier research also revealed that many migraine sufferers have a slightly smaller than average olfactory bulb. Scientists attribute this to the avoidance strategies used by migraine sufferers. Because people with migraine try to avoid certain smell triggers, the neural area responsible for processing olfactory signals shrinks due to a lack of input. Interestingly, at the same time, the pain threshold decreases, leading to increased pain sensitivity.

 

Can smell training work for people with migraine?

To explore whether these changes can be influenced, the research team at Dresden University Hospital conducted smell training with migraine patients. Over four weeks, participants were exposed to subjectively pleasant scents multiple times a day, using “sniff sticks” containing scents such as rose, vanilla, peach or lavender. Smell perception improved as a result, accompanied by a significant increase in the pain threshold compared to a control group — when exposed to induced pain stimuli, treated individuals rated the pain as less intense. The authors of the study concluded that smell training might be a potential method for alleviating pain or even preventing migraine attacks. More extensive research is planned to investigate this promising approach in greater depth.

  • Aktürk T, Tanık N, Serin Hİ, Saçmacı H, İnan LE. Olfactory bulb atrophy in migraine patients. Neurol Sci. 2019 Jan;40(1):127-132. doi: 10.1007/s10072-018-3597-6. Epub 2018 Oct 2. PMID: 30280362.

    Buck L, Axel R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell. 1991 Apr 5;65(1):175-87. doi: 10.1016/0092-8674(91)90418-x. PMID: 1840504.

    Doğan A, Bayar Muluk N, Şahan MH, Asal N, Inal M, Ergün U. Olfactory bulbus volume and olfactory sulcus depth in migraine patients: an MRI evaluation. Eur Arch Otorhinolaryngol. 2018 Aug;275(8):2005-2011. doi: 10.1007/s00405-018-5029-x. Epub 2018 Jun 6. PMID: 29876641.

    Gossrau G, Frost M, Klimova A, Koch T, Sabatowski R, Mignot C, Haehner A. Interictal osmophobia is associated with longer migraine disease duration. J Headache Pain. 2022 Jul 15;23(1):81. doi: 10.1186/s10194-022-01451-7. PMID: 35840888; PMCID: PMC9284850.

    Lötsch J, Hähner A, Gossrau G, Hummel C, Walter C, Ultsch A, Hummel T. Smell of pain: intersection of nociception and olfaction. Pain. 2016 Oct;157(10):2152-2157. doi: 10.1097/j.pain.0000000000000599. PMID: 27152690.

    Mignot C, Faria V, Hummel T, Frost M, Michel CM, Gossrau G, Haehner A. Migraine with aura: less control over pain and fragrances? J Headache Pain. 2023 May 17;24(1):55. doi: 10.1186/s10194-023-01592-3. PMID: 37198532; PMCID: PMC10189721.

    Rottstaedt F, Weidner K, Strauß T, Schellong J, Kitzler H, Wolff-Stephan S, Hummel T, Croy I. Size matters - The olfactory bulb as a marker for depression. J Affect Disord. 2018 Mar 15;229:193-198. doi: 10.1016/j.jad.2017.12.047. Epub 2017 Dec 28. PMID: 29324366.

    Schlenger, R.L. Geruchssinn und Migräne: Wenn der Schmerz zu riechen ist. Dtsch Ärztebl 2021; 118(50): A-2398 / B-1965.

    Silva-Néto RP, Rodrigues ÂB, Cavalcante DC, Ferreira PH, Nasi EP, Sousa KM, Peres MF, Valença MM. May headache triggered by odors be regarded as a differentiating factor between migraine and other primary headaches? Cephalalgia. 2017 Jan;37(1):20-28. doi: 10.1177/0333102416636098. Epub 2016 Sep 30. PMID: 26924838.

    Sjöstrand C, Savic I, Laudon-Meyer E, Hillert L, Lodin K, Waldenlind E. Migraine and olfactory stimuli. Curr Pain Headache Rep. 2010 Jun;14(3):244-51. doi: 10.1007/s11916-010-0109-7. PMID: 20490744.

    Weiss J, Pyrski M, Jacobi E, Bufe B, Willnecker V, Schick B, Zizzari P, Gossage SJ, Greer CA, Leinders-Zufall T, Woods CG, Wood JN, Zufall F. Loss-of-function mutations in sodium channel Nav1.7 cause anosmia. Nature. 2011 Apr 14;472(7342):186-90. doi: 10.1038/nature09975. Epub 2011 Mar 23. PMID: 21441906; PMCID: PMC3674497.

    Zufall F, Pyrski M, Weiss J, Leinders-Zufall T. Link between pain and olfaction in an inherited sodium channelopathy. Arch Neurol. 2012 Sep;69(9):1119-23. doi: 10.1001/archneurol.2012.21. PMID: 22733046.

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