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

Abstract

Objective

To assess the efficacy of topical capsaicin in the treatment of vulvar vestibulitis syndrome.

Study Design

Thirty-three consecutive women referred for vulvar vestibulitis syndrome were treated with topical capsaicin 0.05 %. The capsaicin cream was applied twice a day for 30 days, then once a Day for 30 days, and finally 2 times a week for 4 months.

Results

In 19 patients (59%), improvement of symptoms was recorded, but no complete remission was observed. Symptoms recurred in all patients after the use of capsaicin cream was discontinued. A return to a twice-weekly topical application of the cream resulted in the improvement of symptoms. Severe burning was reported as the only side effect by all the patients.

Conclusion

Response to treatment was only partial, possibly due to the concentration of the compound being too low, or to the need for more frequent than daily applications. The therapeutic role of capsaicin should hence be confined to a last-choice medical approach.

Introduction

The most pressing issue concerning vulvodynia is effective treatment. Vulvodynia, a vulvar discomfort mainly characterized by an individual's complaint of irritation, burning, stinging and/or rawness,[1] may be divided into many subtypes. Among them, vulvar vestibulitis syndrome (VVS) is the most common, and a major cause of chronic vulvar discomfort.[2] VVS is a chronic, persistent clinical entity characterized by severe pain on vestibular touch or attempted vaginal entry, as well as acute tenderness to a cotton-swab palpation of the vestibular area. Furthermore, there is no evidence of physical findings, except for a varying degree of vestibular erythema.[3] Vestibular pain can develop either gradually, following a period of pain-free intercourse, or during the first intercourse attempt. Hence, some authors have classified the latter case as primary VVS, and the former as secondary.[4] Any stimulus that results in pressure on the vulva--including intercourse, tampon insertion, tight-fitting clothing, and cycling--can intensify pain.

The etiology of VVS is unknown. As has been postulated for many chronic pain syndromes, alterations of neural functioning in the vulva of patients with VVS has been suggested recently.[5,6] Some authors have demonstrated reduced vestibular pain thresholds in patients with VVS, raising the possibility of more generalized pain disorder.[7,8] The hypothesis is that persistent nociceptive input from locally acting noxae at the vestibular area leads to central sensitization followed by hyperalgesia and pain. In fact, a vestibular nerve fiber proliferation has been reported in VVS patients (nerve hyperplasia and/or sprouting), and an increased sensitization of thermoreceptors and nociceptors was also found in their vestibular mucosa.[9,10]

Treatment is controversial. Medical,[11] surgical,[12-14] and electromyographic biofeedback treatments[15] have all been tried, with varying degrees of success. An interesting finding of beneficial treatment of VVS with capsaicin was reported by Friedrich in 1988.[16] Treatment with capsaicin 0.025% achieved significant reduction in, or disappearance of, pain and tenderness.[16] The finding has remained isolated, however, as we have found no subsequent published data that confirm these results . Our rationale to investigate capsaicin as a potential therapy for VVS is related to the most recent hypothesis that persistent nociceptive stimuli trigger hyperalgesia and pain in this syndrome; an increased vanilloid receptor (VR1) innervation has also been found in vulvodynia.[17] In fact, capsaicin acts as an agonist of specific vanilloid receptors located on the sensitive peripheral terminals of nociceptors.[18] The application of capsaicin to skin or mucous membranes produces irritation and hyperesthesia; after the initial exposure, capsaicin produces a long-lasting desensitization to burning and pain.[19] This is the basis for positing a neurogenic mechanism as a rationale for capsaicin use in VVS patients. The mode of capsaicin action and the above-mentioned and, so far, unconfirmed report elicited our interest in this compound.

Materials and Methods

Thirty-three women affected by VVS took part in the study; they were informed about the study and gave their consent. Diagnosis was in accordance with Friedrich's criteria.[3] Cultures of the vagina for Candida, Trichomonas vaginalis, bacteria, Chlamydia trachomatis, mycoplasma, and ureoplasma were negative. Pap smear and colposcopic examinations were negative for human papillomavirus. Vulvoscopy indicated vestibular erythema in 29 women. All of the patients had previously undergone different topical therapies without success. The average age was 34.2 years (range, 21 to 55 years), and the average duration of the disease was 15.4 months (range, 6 to 36 months). Of the 33, 15 women were on oral contraception when VVS was diagnosed.

Treatment consisted of a cream preparation of capsaicin powder (0.05 %) in hydrophilic means with glycerine and wax. Since capsaicin is known to cause intense burning, a lidocaine + prilocaine cream was applied 20 minutes before the actual treatment. Patients were instructed to apply about 1/4 teaspoon of the cream to the vestibular area, twice a day for 30 days, then daily for an additional 30 days, and finally 2 times a week for 4 months.

Patients agreed to abstain from sexual intercourse for the first month of therapy. They were scheduled for follow-up examinations after 4, 8, and 16 weeks of treatment and subsequently every 6 months. At first visit and at each follow-up assessment, symptoms of irritation and burning were assessed on a visual analogue scale; dyspareunia was graded on a scale of 0 to 3, where 0 stands for absence of the symptom, 1 for mild pain, 2 for moderate pain, and 3 for severe pain that makes intercourse impossible. All of the women completed a follow-up program of at least 18 months.

Results

Thirty-two women completed the therapy protocol. One patient abandoned the therapy after using capsaicin cream for 5 days due to intense burning. In 19 patients (59%), improvement of symptoms was recorded (Table 1), but none reported complete remission. In these women, a mean 100-mm visual analogue scale was 67.3 before treatment and 15.8 after 8 weeks; whereas dyspareunia ranged from a baseline score of 2.7 to 1.0 after 8 weeks of treatment. Symptoms recurred in all of the patients an average of 15 days after they had stopped using the capsaicin cream. Symptoms improved again about 20 days after the twice-weekly topical application of capsaicin was resumed. Thirteen patients (41%) didn't show improvement of any kind despite using capsaicin for 2 months. According to baseline symptom scores, factors such as age, duration of disease, use of oral contraceptive, and primary vs secondary VVS, there was no significant difference between women who had pain reduction compared with those who did not.

Table 1.

Mean 100-mm Visual Analogue Scale of Vulvodynia and Mean 0-3 Dyspareunia Score Before and After 4, 8, and 24 Weeks of Treatment With Capsaicin 0.05% Cream

	Baseline	4 weeks	8 weeks	24 weeks
Vulvodynia (irritation, burning)	67.30	18.94	15.78	15.78
Dyspareunia	2.7	1.2	1.1	1.0

Burning was reported as the only side effect, but it was reported as severe by all of the patients. It occurred 20 to 30 minutes post application, in spite of pretreatment with anesthetic cream; it abated 40 to 60 minutes later, and decreased at each subsequent application in the majority of patients. In 1 case, it was so severe that the patient abandoned treatment. No systemic effects were observed.

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.