Treatment of Localized Vulvar Pain with Neural Therapy: A Case Series and Literature Review

Localized vulvar pain (LVP), previously known as vulvar vestibulitis or localized vestibulodynia, is defined as chronic pain and/or stinging located in the vulvar vestibule or the clitoris, without an identifiable cause that persists for 3 months or more. It can be provoked (most frequently), spontaneous, or mixed [1].

LVP is the most common subtype of chronic vulvar pain [2], with an unknown prevalence and incidence. The prevalence of chronic vulvar pain is estimated between 3 and 15% [3‒5]. Many women affected by vulvar pain do not seek medical advice; only 50% do, and among them, only a minority (1.4%) are diagnosed with vulvodynia [6]. LVP has a negative impact on health, self-esteem, mood, relationships, and quality of life for women who suffered from it [7, 8].

Although different etiopathogenic mechanisms have been proposed, no definitive cause has been defined. The 2 main etiopathogenic mechanisms are [6, 9]: neurogenic origin due to damage of peripheric nervous terminations (vestibular) and inflammatory origin due to chronic inflammation process in the vestibule with peripheric sensitization [10]. Both mechanisms would produce central sensitization (spinal cord) and change nociceptive transmission in the central nervous system, perpetuating pain.

The diagnosis is clinical, excluding specific causes of vulvar pain, such as infection, inflammation, neoplastic or atrophic diseases [6].

Although different treatments have been proposed, there is no specific treatment. A multidisciplinary approach is proposed considering the following interventions: medication, psychosexual therapy, physical therapy, neuromodulation procedures, and surgery techniques [11]. None of the proposed treatments is effective in permanently eliminating symptoms. The search for new therapeutic approaches for LVP is a need and a challenge [9].

Neural therapy (NT) is a regulatory treatment that consists of an injection of local anesthetics (LA), at low concentration (0.5 or 1%), into specific points with a therapeutic and diagnostic purpose, local anesthesia not being the goal (except for diagnostic issues) [12, 13]. The most widely used LA in NT is procaine, due to its safety profile, its prolonged action beyond pharmacological duration, and its additional favorable effects on microcirculation [12, 14]. The objective is the generation of a directed stimulus (through the needle) and the selective extinction of other stimuli (through the LA), thus affecting the nervous system and tissue perfusion [15] and allowing the interruption of positive feedback loops (vicious circles) of pain and other pathological processes [12, 13, 15]. The treatment modalities in NT are local therapy (injection in trigger points and in areas of tension or pain on palpation) [16]; segmental therapy (injection in reflex areas of HEAD, sympathetic ganglia, nerve roots, or peripheral nerves) [12, 13]; and interference field therapy (injection into areas of chronic alteration of a structure of the organism that can cause or maintain a symptomatic alteration in another area of the organism) [10, 12, 13].

We present a case series of 5 women with LVP treated with procaine 0.5% injections in painful vulvar points (local therapy modality of NT). All patients were attended as outpatients in a gynecology unit of a tertiary hospital between October 2016 and October 2017. The technique consisted of injecting at the painful points between 0.5 and 1 mL of 0.5% procaine with hydrochloric acid as excipient (Procaine Serra), with a hypodermic needle of 0.30 × 12 mm (30 G × 1/2 Sterican Braun) at the subcutaneous level (depth between 1 and 2 mm). Pain related to LVP was measured by the visual analogue scale (VAS) of 0–100 (VAS =  0, no pain; VAS  =  100, maximum pain).

The purpose of this case report is to motivate future studies to evaluate the efficacy of local procaine injections to treat LVP.

A 33-year-old single Caucasian woman with provoked LVP for 5 months reported to the gynecology department. She had a body mass index (BMI) of 22.3, was nulliparous, used oral combined hormonal contraception (OCHC), and suffered from polycystic ovary syndrome and recurrent candida vulvovaginitis (2 episodes at age 21 years and 1 at 28 years).

She had suffered from vulvar pain for 5 months that appeared immediately after genital contact or manipulation and had itching characteristics. The duration of pain was from 48 to 72 h after the onset and intensity measured by VAS was 70. She was unable to have sex or insert tampons.

On examination, no discoloration changes were observed either in the vagina or in the vulva, and the flow was normal. Vestibular palpations at 5 and 7 h were painful. It was defined as provoked LVP. No previous treatment had been made.

Procaine 0.5% injection was performed on painful localizations (5- and 7-time zones). The patient presented pain of VAS = 20 and scarce self-limiting bleeding related to the punctures. VAS after the intervention improved from 70 to 20, always associated with vulvar contact or manipulation. The improvement was maintained during the follow-up period (16 months) without relapses.

A 35-year-old married Caucasian woman reported to the department of gynecology with provoked LVP. She complained of vulvar pain for 36 months of evolution. She had a BMI of 25.7 and suffered from dysmenorrhea and endometriosis, with ovarian cystectomy at age 28 years. She had had 2 deliveries, the first with Cesarean section at age 29 years and the second with episiotomy and forceps at age 29 years, complicated by scar dehiscence that required 2 reparative interventions (the last at age 35 years). She used OCHC.

The vulvar pain, starting after the last reparative intervention for scar dehiscence, had itching and burning characteristics and was provoked by vaginal manipulation or contact, preventing intercourse and the application of tampons. Physical examination revealed vestibular palpation pain at 5- and 8-time zones without other abnormalities. The diagnosis orientation was provoked LVP. VAS at first visit was 100.

Two sessions of procaine 0.5% injection were performed with an interval of 4 weeks on painful points (5- and 8-time zones). The patient presented pain of VAS = 20 and scarce self-limiting bleeding related to the punctures. VAS after the intervention was 0. The pain did not reappear during the follow-up period of 7 months. The patient was able to resume the use of tampons and intercourse normally.

A 33-year-old married Caucasian woman reported to the gynecology department for provoked LVP for 18 months of evolution, starting after delivery. The pain appeared immediately after genital contact or manipulation with a VAS intensity of 100, persisting for 2 h after contact. The pain prevented any genital contact, so she was not able to partake in sexual practices. She had a BMI of 26.5, had had 1 delivery with episiotomy at age 31 years, and used condoms as contraception. As a medication, she received promestriene (vaginal) and chlorhexidine (topical).

Physical examination revealed episiotomy scar and vestibular palpation pain at the 5-time zone without other abnormalities.

Procaine 0.5% injection in a painful point, localized in the 5-time zone, was performed. She reported pain of VAS = 70 for a very brief duration (just at the puncture time) and scarce self-limiting bleeding related to the puncture. VAS after the intervention was 0.

The patient was able to resume intercourse and the use of tampons. There were no relapses during the follow-up period of 18 months.

A 44-year-old married Caucasian woman with mixed LVP (provoked and spontaneous) for 4 months presented to a gynecology consultant. She had a BMI of 25.3 and suffered from dysmenorrhea. She had had 1 delivery by vacuum and episiotomy at age 35 years and used OCHC. She was on treatment with fluomizin (vaginal), antifungal (topical), and corticosteroids (topical).

The patient reported pain with itching and burning characteristics with baseline VAS = 80 that increased to VAS = 100 with any vulvar manipulation or contact. The pain impaired intercourse or the use of tampons. She had received various treatments before consultation: antifungal treatment for 7 days, vaginal dequalinium chloride ovules (fluomizin) for 6 days, topical corticosteroids for 2 weeks, and moisturizing creams (active treatment at consultation). None of these treatments had improved LVP.

Physical exploration revealed episiotomy scar and painful palpation at the 5-time zone without other abnormalities.

Procaine 0.5% injection (0.5 mL) was performed in the 5-time zone in 2 sessions with an interval of 4 weeks. After the first session, the pain decreased from VAS = 100 to 50, and after the second session from 50 to 30. She presented pain of VAS = 20 and scarce self-limiting bleeding related to the punctures.

The improvement was maintained during the follow-up of 10 months. The patient was able to resume coitus and the use of tampons.

A 33-year-old married Caucasian woman with a prior medical history significant for Crohn’s disease and hypothyroidism reported provoked LVP for 36 months. She had a BMI of 20.9 and suffered from dysmenorrhea and endometriosis. She had had 1 delivery at age 30 years with forceps and episiotomy (suffering from perineal second-grade tear). She used OCHC and vaginal ring. In addition, she had recurrent vulvovaginitis from age 25 years with the last episode at 32 years, having treatment with antifungal, either oral or topical in each episode. She was on treatment with azathioprine (oral), mesalazine (rectal), and levothyroxine (oral). She complained from vulvar pain immediately after contact with burning and itching characteristics and VAS = 70. The pain impaired intercourse and the use of tampons.

Physical exploration revealed pain in the 5-time zone and episiotomy scar without other abnormalities.

Procaine 0.5% (0.7 mL) injection was performed into the 5-time zone and episiotomy scar (painful points) in 2 sessions with an interval of 4 weeks. She presented pain of VAS = 20 and scarce self-limiting bleeding related to the punctures. After the first intervention, pain improved from VAS = 70 to 40, and after the second, VAS decreased to 30. The patient was able to resume intercourse and the use of tampons. There were no relapses during the follow-up period of 18 months.

Table 1 summarizes the demographic and clinical characteristics of the women; Table 2 describes the main characteristics of LVP; and Table 3 summarizes treatment and clinical evolution.

In our case series, subcutaneous procaine injection was found to be a fast and safe treatment for LVP. Since it is a minimally invasive technique, the treatment can be performed on an outpatient basis. The fact that only 1 or 2 sessions resolved a chronic problem is another outstanding result of this technique. The fact that patients could resume sexual intercourse after the intervention is another remarkable point.

To our knowledge, this is the first case series to describe subcutaneous procaine injection to treat LVP.

Topical application of LA is one of the most commonly prescribed treatments for vulvodynia [17]. In contrast, repeated applications of lidocaine are considered an elective treatment for this condition with variable outcomes. A common side effect is stinging, which causes many patients to discontinue treatment [9]. In contrast, subcutaneous injections of procaine 0.5% in our series of cases were shown to improve symptoms, requiring only 1 or 2 sessions. The difference in the route of administration of LA (subcutaneous versus topical) could influence the different outcomes and treatment tolerance. The generation of a directed stimulus (caused by the needle) and the selective extinction of other stimuli (by means of LA) could have an impact on the organization of the nervous system and tissue perfusion, interrupting positive feedback actions (vicious circle) of pain [12, 13, 15].

The infiltration with ropivacaine of the impar ganglion has been previously described for treatment of rebel vulvodynia with good favorable results in a case series with 8 patients [18]. The main difference in our case series is the requirement of computed tomography and contrast injection. In addition, in 2 patients botulinic toxin was also administrated. As in our case series, the improvement was maintained over time without requiring other treatments during the follow-up period.

Weinschenk et al. [10] reported a case of long-lasting vulvodynia successfully treated with repeated injections of procaine 1% in HEAD’s zone and trigger points of different locations and interference fields (abdomen, hypogastrium, maxillary, and scar jaw). The patient received 14 sessions and the improvement was maintained in the follow-up period. The main differences from our case series are the number of injections (much lower in our case series) and the points of injections (distant from the vulvar area in that case vs. exclusively in the vulvovaginal area in our case series).

In our case series, the adverse effects were limited to a brief pain at the puncture site without residual discomfort afterwards. This finding coincides with the results of other studies in the medical literature, considering the injection of LA at low concentrations as a safe intervention in the management of pain control [10, 12, 18‒20].

The therapeutic effect of LA has been mainly related to their nerve-blocking properties, secondary to their interaction with the Na²⁺ channels. During the last few decades, a wide range of attributes, beyond their anesthetic effect, have been related to LA, probably due to their action over the K⁺ and Ca²⁺channels [21], inhibitory actions on the receptors coupled to the protein G [14], and inhibitory action on the N-methyl-D-aspartate (NMDA) receptors [22, 23].

The modulating effects of LA on the immune system have been widely described [14, 24], and different mechanisms of action have been proposed [14, 25‒36]: leucocyte inhibition, decrease in synthesis and release of inflammatory mediators, and decrease in vascular hyperpermeability and edema formation (Table 4).

The modulating effects of LA on the neural system have also been previously described in the medical literature. LA may interrupt the vicious circle of nociceptor acting over different pathogenic mechanisms involved in pain perception, such as sympathetic excitation, vascular alteration, neurogenic inflammation, and muscular contraction [12, 14].

Our case series raises the question about the role of LA in the treatment of chronic pain and their long-acting analgesic action. In the medical literature, we find reports about the therapeutic effects of LA beyond their anesthetic local effect, showing favorable evolution of chronic pain treated with injections of LA [12, 13, 37‒41]. Puente de la Vega Costa et al. [15] summarize the following mechanisms of action of the LA to explain their lasting effects on pain: reduction of long-term potentiation in the sympathetic ganglia [42, 43], decrease of sympathetic sprouting related to sympathetic-afferent coupling [44‒46], decrease of the inflammation related to vasomotor phenomena [47], decrease of the release of proinflammatory neuropeptides from sympathetic fibers [14, 47], decrease of the sympathetically mediated activity of wide dynamic range neurons [48], interruption of interaction between the sympathetic nervous system and immune system [47, 49], temporary interruption of the positive feedback neuronal circuits (“reset”), with the involvement of the sympathetic nervous system at the spinal and supraspinal levels and the subsequent reorganization of the systems involved [12, 13].

The etiopathogenic mechanisms related to LVP described previously are focused on a neurogenic and/or inflammatory origin. Regardless of whether LVP starts with nerve injury or a chronic inflammatory process, the alteration (irritation) of the vestibular nerve endings and the modification of nerve transmission occur originating anomalous impulses [50]. This causes peripheral sensitization that, when maintained over time or by very intense stimuli, gives rise to central sensitization and perpetuation of pain [12]. Treatment with local modality of NT could eliminate the anomalous stimuli of the central nervous system and, consequently, resolve the pain.

None of the treatments proposed up to now for LVP have shown to be effective in permanently improving the symptoms. The results of our case series of 5 patients with LVP suggest that local injection with procaine may be an option to consider, whether it is applied primarily or after insufficient standard procedures. Well-designed studies should be done to assess the efficacy of this treatment in LVP.

We thank Paloma Lobo Abascal for her comments on the article. We also thank all the women who participated in the study.

An informed consent was obtained for this minimally invasive treatment modality. All patients gave their informed consent for the publication of this study.

The authors declare that they have no competing interests.

The authors received no external funding to conduct this study.

M.R.N. conceived the idea, carried out the fieldwork, and contributed to drafting the manuscript and reviewing the literature. M.M.-S. wrote the final manuscript and contributed to reviewing the literature. M.C.S. contributed to drafting the manuscript. D.V.C. contributed to reviewing the literature and revised the paper. All authors read and approved the final manuscript.