Pelvic pain is a common disorder in women, causing significant morbidity. Often the etiology is not clear as it results from a complex interaction between neurologic, musculoskeletal and endocrine systems that is further influenced by behavioral and psychological factors. A comprehensive approach to the problem requires recognition of the multiple organ systems that may be involved. A thorough history and physical examination, followed by selected laboratory and imaging studies, is essential in evaluation of these patients. Medical and surgical management improves or controls the symptoms in the majority of cases, but there remains a group of women who are difficult to treat. Botulinum toxin is a presynaptic neuromuscular blocking agent inducing selective and reversible muscle weakness that lasts several months when injected intramuscularly. It has been shown to be effective in treating pain caused by muscular spasm in conditions other than pelvic pain caused by muscular hypertonicity.
Endometriosis occurs when the uterine tissue lining grows outside of the uterus and is estimated to affect up to 176 million women worldwide. It is an inflammatory condition that can lead to infertility and cause chronic pain. The usual gynecologic treatments include hormonal therapy and surgery to remove the growths. However, in many cases, pain returns after the interventions.
In the study conducted by scientists at the National Institute of Neurological Disorders and Stroke (NINDS),women with surgically treated endometriosis who were generally taking hormones to suppress menses, but who continued to experience pain and had pelvic floor muscle spasm, initially received injections of botulinum toxin or saline as part of a placebo-controlled clinical trial, targeting areas of spasm. At least one month after the masked study injection, 13 participants chose to receive open-label botulinum toxin injections in areas that remained in spasm and were then followed for at least four months. These patients were described in the current study at the NIH Clinical Center. The participants experienced a decrease in muscle spasm and had pain relief that resulted in less disability and less use of pain medication. These findings suggest that pelvic floor muscle spasm may be experienced by women with endometriosis and contribute to pain persisting after standard treatment. Importantly, the beneficial effects were long-lasting, with many patients reporting pain relief lasting at least six months.
Countless women suffer from this debilitating condition: the scant population data available suggest a prevalence of 8–13%.Vaginismus is generally thought to be under-reported, it is frequently undiagnosed and it is sometimes inappropriately treated with surgical interventions, such as Fenton’s procedure. It is a psychosomatic condition causing involuntary contraction of the muscles surrounding the vagina, which either makes penetrative intercourse painful or prevents it altogether. The pain is usually described as stinging or burning in nature and the association of intercourse with pain leads to avoidance,which frequently has a serious negative impact on relationships. It is commonly triggered by relationship problems, feelings of guilt about sex, or past sexual abuse, but the causes are legion and can be difficult to determine. In addition to causing sexual difficulties, it can make gynaecological examination and the taking of cervical smears difficult or impossible.Women with vaginismus have been shown to have increased pelvic muscle tone,an increased frequency of defensive/avoidance distress behaviour during pelvic examination, and they recall attempts at intercourse with more affective distress.
Botulinum toxin should not be seen as a substitute for more traditional methods of managing this distressing condition, namely psychosexual counselling using psychotherapeutic or behavioural techniques. It may, however, prove to be a useful adjunct to treatment in the same way that sildenafil has been used to help men with erectile dysfunction of psychogenic origin.
Vulvar vestibular syndrome or vulvar vestibulitis encompasses the terms vulvodynia and vestibulodynia, which describe slightly different distributions of a condition characterised by altered pain perception in the vulval area. The pain is characterised by extreme tenderness to pressure and it is a common impediment to sexual intercourse. Studies have shown that these women also have increased pelvic muscle tone. The treatments used included: local anaesthetic gel; biofeedback to reduce pelvic muscle tone; tricyclic antidepressants; other drugs used for neuropathic pain, such as carbamazepine and gabapentin; hypnosis and surgical vestibulectomy.
A retrospective study (Yoon, H.; Chung, W.S.; Shim, B.S. Botulinum toxin A for the management of vulvodynia) recruited seven women aged 28–61 years with intractable genital pain that was refractory to conventional treatment. Twenty units of BoNT-A was injected into the pain sites including the vestibule, levator ani muscle and the perineal body. If the symptoms had not subsided totally, 40 U of BoNT-A was injected repeatedly every two weeks. After BoNT-A injections, pain decreased or disappeared in all patients. The mean VAS score decreased to 1.4 from 8.3 before the treatment, with no recurrence. The study showed improvement of sexual life without significant pain or discomfort during or after sexual activity.
The pelvic floor is comprised of a number of muscles and they are organized into superficial and deep muscle layers. There is significant controversy with regards to the nomenclature, but generally speaking the superficial muscle layer and the muscles relevant to the anal canal function are the external anal sphincter, perineal body, and possibly the puboperineal (or transverse perinei) muscles. The deep pelvic floor muscles consist of pubococcygeus, ileococcygeus, coccygeus, and puborectalis muscles. Puborectalis muscle is located in between the superficial and deep muscle layers, and it is better to view this as the middle muscle layer of the pelvic floor. In addition to the skeletal muscles of the pelvic floor, caudal extension of the circular and longitudinal smooth muscles from the rectum into the anal canal constitutes the internal anal sphincter and external anal sphincter of the anal canal, respectively.
The pelvic diaphragm, first so named in 1861 by Meyer, included primitive flexors and abductors of the caudal part of the vertebral column. These muscles included coccygeus (also referred to as ischiococcygeus), ileococcygeus, and pubococcygeus and these three muscles are believed to constitute the levator ani muscle. They originate from the pectinate line of the pubic bone and the fascia of the obturator internus muscle and are inserted into the coccyx. It seems that the puborectalis muscle originates from the middle of inferior pubic rami rather than from the pubic symphysis. The puborectalis muscle is now included in the levator ani muscle group and the term ‘‘levator ani’’ is used synonymously with pelvic diaphragm muscles.
Branches from the sacral nerve roots of S2, S3, and S4 innervate the pelvic floor muscles. There is considerable controversy, however, as to whether the pudendal nerves actually innervate the levator ani muscles. It is possible that the puborectalis muscle (middle layer of pelvic floor muscle) is actually innervated by the pudendal nerve (from below) and the deep muscles (pubococcygeus, ileococcygeus, and coccygeus) are innervated by the direct branches of sacral nerve roots S3 and S4.
There are three major mechanisms of botulinum toxin that function on the muscles, neural system, and inflammation to relieve pain symptoms. Botulinum toxin plays an important function in the reduction of pain symptoms. It is believed that spasms and tenderness of the PFMs are highly associated with CPPS in women. Botulinum toxin injection has been used to paralyze muscles, and its effect is localized, partial, and reversible. After injecting in to the pelvic floor muscles, botulinum toxin can reduce the hypertonic pressure and improve pelvic muscle spasms.
Botulinum toxin A (BoNT-A) is a selective neurotoxin that acts on neuromusculatures. After binding to terminal receptors on the motor neuron, it can inhibit the release of ACh to cause muscle paralysis. BoNT-A inhibits ACh vesicles releasing to the synaptic cleft by cleaving particular proteins, such as SNAP-25 or VAMP, which are essential for binding with ACh vesicles at the presynaptic membrane. Due to the effect of BoNT-A, there is no release of ACh in the synaptic cleft, and it can paralyze the innervated muscles subsequently. This mechanism has been used to relieve the storage of lower urinary tract symptoms of IC/BPS such as frequency and urgency.
In addition, BoNT-A has the analgesic effect of relieving pain symptoms. Animal and human studies have shown that increased expression of cell membranes receptors, such as the TRPV1 in the nociceptors may up-regulate the symptoms of neuralgia. BoNT-A has been reported to reduce the expression of TRPV1 in rats with neuropathic pain.
After the injection of BoNT-A, paralysis of muscle occurs after 2–5 days. The functional effects can typically last from three to six months. The clinical efficacy of BoNT-A injection for CPPS in women was durable to 24 weeks. This long-term but reversible effect has made BoNT-A an important therapy for a wide variety of neuromuscular diseases.
The procedure is usually done on an outpatient basis. Ultrasound can be used for infiltration of the pelvic floor muscles.The muscles that are commonly targeted include pubococcygeus, iliococcygeus, ischiococcygeus, piriformis, obturator internus and deep and superficial transverse perinei mucles. A total of 100 to 200 units of botox is injected in to these muscles to reduce the hyper tonicity. Botulinum toxin has temporary effect, so repeat injections may be needed.
Injections are generally avoided in patients with systemic infection or skin infection over puncture site, bleeding disorders or coagulopathy, and allergy to the drugs that are being administered.
Botulinum toxin is contraindicated in patients afflicted with a preexisting motor neuron disease, myasthenia gravis, Eaton-Lambert syndrome, certain neuropathies, psychological unstability, history of reaction to the toxin, pregnancy and lactating females, and infection at the injection site.
Injections with botulinum toxin are generally well tolerated and side effects are few. Generalized idiosyncratic reactions are uncommon, generally mild, and transient. There can be mild injection pain and local edema, erythema, transient numbness, headache, malaise or mild nausea. Its effect diminishes with increasing distance from the injection site, but spread to nearby muscles and other tissues is possible. The most feared adverse effect is temporary unwanted weakness/paralysis of nearby musculature caused by the action of the toxin. It usually resolves in several months and in some patients in a few weeks, depending on the site, strength of the injections, and the muscles made excessively weak.
Post-procedural pain flare-up can occur in some patients, though this is rare with botox injections and more common with steroid injections.