Capsaicin and the Treatment of Vulvar Vestibulitis Syndrome: A Valuable Alternative?

Filippo Murina, MD, Gianluigi Radici, MD, and Vanda Bianco, MD

Disclosures
In This Article

Discussion

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamid) is the lipophilic vanilloid compound that makes hot chili peppers spicy. As well as structurally related molecules, capsaicin is an agonist of specific vanilloid receptors located on the sensitive terminals of nociceptors.[20] It has been recommended as a treatment for a variety of painful syndromes, as repeated topical application of capsaicin releases, and specifically prevents, the reaccumulation of neuropeptides in unmyelinated, polymodal C-type and small myelinated A-delta-type cutaneous nerves. Because nociceptive sensations are mediated by unmyelinated C-fibers and small myelinated A-delta-type neurons, depletion of neuropeptides upon continuous application of capsaicin impedes the perception of pain and itchy sensations, whereas tactile sensations remain unaffected.[21]

Vestibular tissue removed from women who underwent surgery for VVS has been analyzed for nerve fiber density and the presence of mast cells; a significant increase in both the number of mast cells and the number of intraepithelial nerve endings, which are coarse and thickened, was reported.[22,23] Thus VVS seems to be a complex regional pain syndrome, but other neuropathic pain mechanisms have also been postulated in the past few years, including a central sensory processing abnormality (accounting for syndromes such as increased headaches, fibromyalgia, and irritable bowel, that often accompany VVS). Relief of symptoms is possibly related to blockage of C-fiber conduction and inactivation of neuropeptide release from peripheral nerve endings, thus accounting for local antinociception with degeneration of epidermal nerve fibers.[24]

As to the only partial response to treatment that we report here, some hypotheses may be postulated, the foremost being that the concentration of the compound used may have been too low. Clinical investigations of topical capsaicin include trials dealing with chronic pain syndromes such as postherpetic neuralgia and diabetic neuropathy, and on the basis of the results of these studies, capsaicin should be applied at least 3 to 5 times a day with a 0.025% to 0.075% concentration.[20] In Friedrich's 1988 report of successful treatment of VVS with capsaicin, the concentration used was 0.025%.[16] However, tachyphylaxis may result from increasing capsaicin concentrations and from an irregular application strategy. Hence, we chose an overall lower dose (0.05%, twice a day to begin with, and the dosage was lowered with ongoing treatment), even though topical application of capsaicin has never been reported to cause systemic effects. This fact is of crucial importance because it has been shown with systemic administration of capsaicin and with capsaicin treatment of cultured sensory neurons that the agent can potentially damage C-type nerves in an irreversible manner as a result of the activation of intracytoplasmic calcium-sensitive proteases.[25]

Friedrich[16] reported the results for about 6 patients. In 4 cases, a significant reduction or complete remission of pain and tenderness was observed. This is the only published study about capsaicin use for treatment of VVS. No results or discussion about follow-up are presented. Ever since, however, capsaicin has been cited as a possible treatment for VVS.

In our series, complete remission was not observed, although the rate of satisfactory results is similar to those reported for most topical treatments of VVS, including Friedrich's report. In addition, prompt recurrence of symptoms in all responding patients after treatment was suspended suggests a symptomatic effect of treatment without curative efficacy, unless a persistent response could be demonstrated using higher doses. This is a disadvantage of this therapeutic approach, although, interestingly, the efficacy of capsaicin is promptly re-established with return to treatment at maintenance dosage. Recurrence of symptoms might be due to the reaccumulation of neuropeptides in unmyelinated, polymodal C-type vestibular fibers with reinnervation of the epidermis.[25] The second disadvantage is that all patients complained of severe burning at the site of capsaicin application, albeit transient, due to the primary release of neuropeptides. In addition, burning with application of capsaicin may be responsible for the absence of complete remission of symptoms, a finding different from the myriad of treatments tried for VVS for which there has always been at least a small number of fully responding patients.

Pretreatment with lidocaine + prilocaine cream was meant to reduce the burning and attenuate heat hyperalgesia expected on treatment. The time lapse between the capsaicin application and the occurrence of the side effect of burning suggests that the anesthetic application may have been useful. Where necessary, a second application of lidocaine + prilocaine cream after capsaicin might help make the burning more tolerable. Whether the anesthetic cream itself could be responsible for the results must also be considered. In some studies, topical anesthetics, such as lidocaine jelly, have been thought to relieve discomfort temporarily and make intercourse possible in some milder cases of vulvar pain. Unfortunately, the effects last for a couple of hours only, and repeated applications can cause damage to the underlying skin.[26]

There are several possible reasons why 13 women did not respond and why those who did respond experienced only partial remission of vulvodynia: too low concentrations of capsaicin, too long a time interval between applications, incomplete cream absorption, and incorrect application.

In conclusion, although capsaicin has been cited as a possible treatment approach to the VVS issue,[16,20] its role must be confined to a last-choice medical approach. In fact, the finding of only a partial response, the severe burning as an important side effect, and the need for continuing treatment largely limit the practicality of capsaicin therapy. Most of the published studies about VVS treatment have been criticized for sample size, lack of a control group, and unclear inclusion and exclusion criteria. The addition of a control group (with lidocaine cream, for example) to our study would no doubt have made the results more meaningful.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....