Repeated intranasal capsaicin applications to treat chronic migraine

B. M. Fusco, G. Barzoi and F. Agrò

Rome, Italy

Editor—Capsaicin is a useful tool in studying pain pathways, because of its specificity of action on nociceptive fibres.1 It acts on the recently cloned polymodal vanilloid receptor-1 (VR1) which responds to stimulation by thermal and pH changes as well as to vanilloids, such as capsaicin. The VR1 has been localized on sensory neurons and within the central nervous system. Exposure of peripheral nociceptive fibres to the drug not only stimulates the sensory function of the fibres but also causes the peripheral release of active neuropeptides, such as substance P and calcitonin gene-related peptide. In man, in vivo, this corresponds to the burning sensation and reddening, which are observed after local application of capsaicin. Repeated administration of capsaicin results in block of the VR1 with a consequent refractoriness of nociceptive fibres, however, which become insensitive not only to capsaicin, but also to other stimuli.2 This desensitizing effect suggests that capsaicin is a potential therapeutic tool in pain therapy.3 In fact, capsaicin has been shown to be effective in the treatment of post-herpetic neuralgia, diabetic neuropathy, osteoarthritic pain, and trigeminal neuralgia.46

Cluster headache has also been significantly improved by treatment with repeated applications of an emulsion containing capsaicin, which was applied in the nostril homolateral to the attacks.7 In contrast, the results of the same treatment in patients suffering from episodic migraine did not have the same effect, probably because of the variability in the frequency of migraine attacks (personal communication). Chronic migraine, also known as ‘transformed migraine’, is a common condition characterized by a progressive increase in the frequency of attacks until the headache is permanently present, with frequent exacerbations (1–2 per week).8

We have evaluated the effect of repeated intranasal administration of capsaicin on chronic migraine. Eight patients affected by chronic migraine were enrolled. In this double-blind study, four patients were randomly assigned to a capsaicin group and four to placebo. Patients in the capsaicin group received 100 µl of an emulsion containing capsaicin 300 µg dissolved in 80% saline solution, 10% paraffin oil, and 10% polyethylene glycol sorbitan monooleate (Tween® 80, Sigma-Aldrich), applied in both nostrils once a day for 7 days. The composition of the emulsion and the method of administration were the same as a previous study, which was carried out in cluster headache patients;7 a single daily administration was chosen in order to reduce the burning sensation experienced after each capsaicin application.

In order to mimic the decreasing burning sensation in the placebo group, with daily administration, these patients each day received solutions of increasing pH (+0.5 pH each day) ranging from 1.5 to 4.5. This was obtained with decreasing concentrations of citric acid, dissolved in the same emulsion as capsaicin. No other treatments were allowed, except for escape medication (ketorolac 10–15 mg orally) for the exacerbation episodes. For 10 days before and 30 days after the beginning of treatment, a daily evaluation of the intensity of the headache was made using a numerical scale from 1 to 10, as well as an assessment of the treatment by the patient once it had started.

The nasal burning sensation was tolerated in both groups; it lasted about 10 min and no patient dropped out of the study because of it. All patients treated with capsaicin reported an improvement in their migraine, which was judged to be between 50 and 80%. One patient treated with placebo reported a 20% improvement. Statistical evaluation ({chi}2, P<0.01) showed that capsaicin was significantly efficacious compared with placebo.

This preliminary study suggests a therapeutic effect of nasal application of capsaicin in chronic migraine.

B. M. Fusco

G. Barzoi

F. Agrò

Rome, Italy

References

1 Maggi CA, Geppetti P, Santicioli P, et al. Tachykinin-like immunoreactivity in the mammalian urinary bladder: correlation with the functions of the capsaicin-sensitive sensory neurons. Neuroscience 1988; 26: 233–42[CrossRef][ISI][Medline]

2 Szallasi A. Vanilloid (capsaicin) receptors in health and disease. Am J Clin Pathol 2002; 118: 110–21[ISI][Medline]

3 Winter J, Bevan S, Campbell EA. Capsaicin and pain mechanisms. Br J Anaesth 1995; 75: 157–68[Free Full Text]

4 Fusco BM, Giacovazzo M. Peppers and pain: the promise of capsaicin. Drugs 1997; 53: 909–14[ISI][Medline]

5 Rains C, Bryson HM. Topical capsaicin. A review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis. Drugs Aging 1995; 7: 317–28[ISI][Medline]

6 Fusco BM, Alessandri M. Analgesic effect of capsaicin in idiopathic trigeminal neuralgia. Anesth Analg 1992; 74: 375–7[Abstract]

7 Fusco BM, Marabini S, Maggi CA, Fiore G, Geppetti P. Preventative effect of repeated nasal applications of capsaicin in cluster headache. Pain 1994; 59: 321–5[CrossRef][ISI][Medline]

8 Mathew NT, Reuveni U, Perez F. Transformed or evolutive migraine. Headache 1987; 27: 102–7[ISI][Medline]





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