Case Letter

Management of Refractory Pain From Hereditary Cutaneous Leiomyomas With Nifedipine and Gabapentin

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We then increased the patient’s gabapentin regimen to 300 mg in the morning and 600 mg in the evening, as tolerated. The patient reported that she was better able to tolerate the sedating side effects of the increased dose of gabapentin because she had stopped working due to her severe pain episodes. We also added oral nifedipine 10 mg 3 times daily, as needed. Within 30 minutes of starting this treatment regimen, the pain associated with the lesions remarkably improved (10/10 severity before starting treatment vs 3/10 after starting treatment). Her pain levels remained stable (3/10 severity) during 3 weeks of treatment with this combination regimen, but unfortunately she developed headaches and malaise, which she associated with the nifedipine at the 3 times daily dose.

The patient was able to better tolerate the nifedipine after reducing the dose to once daily on an as-needed basis. On average, the patient took nifedipine once every 3 days; however, she reported that she had to periodically increase the frequency of the nifedipine to once daily for up to 2 weeks at a time for periods of more frequent pain flares. The patient reported a consistent pattern of the breakthrough symptoms rapidly improving with each dose of nifedipine, though she did feel that taking consistent gabapentin enhanced baseline symptom control. The patient also noticed on a few occasions when she did not have access to her nifedipine that her pain would flare to 10/10 severity and would decrease to 4/10 severity 30 minutes after restarting nifedipine at 10 mg once daily. She experienced breakthrough pain due to exacerbating factors including her menstrual cycle; exposure to the sun and cold temperatures or water; excessive physical activity; and mild trauma. Due to exacerbations from sun exposure, the patient often wore long-sleeved shirts, which helped reduce the severity of the pain episodes while she was outdoors.

The exact mechanism for the pain associated with cutaneous leiomyomas is unknown but is thought to be due to infringement of the lesion on the surrounding cutaneous nerves. In addition, norepinephrine activates alpha receptors on the smooth muscle to contract through an influx of ions such as calcium. When smooth muscle contracts, the compression of nerves likely is worsened.

There are a limited number of case reports in the literature that have demonstrated successful treatment of the pain associated with cutaneous leiomyomas. Previously reported treatment modalities have included phenoxybenzamine, an alpha-blocking agent that may reduce pain through its antiadrenergic effects2; nitroglycerin, a venous and arterial dilator that may reduce pain by decreasing muscle oxygen requirements2; gabapentin, an antiepileptic and analgesic medication with structural similarity to the gamma-aminobutyric acid neurotransmitter for which the exact mechanism of action is unknown3; botulinum toxin, a neuromuscular blocker that prevents the release of presynaptic acetylcholine and may decrease neuropathic pain by reducing hyperactive nerves5,6; hyoscine butylbromide and topical hyoscine hydrobromide, both antispasmodics that may reduce pain through their anticholinergic effects, which relax smooth muscle7,8; and the CO2 laser, a treatment that has been utilized for its resurfacing, excisional, and ablative properties.9,10

Calcium channel blockers such as amlodipine, verapamil, and nifedipine also have been used to treat the pain associated with piloleiomyomas.11 Calcium ion channel antagonists inhibit the influx of calcium ions across the cell membrane; therefore, nifedipine and other calcium channel blockers may prevent the smooth muscle contraction that is hypothesized to cause pain in patients with cutaneous leiomyomas.12

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