Chronic pelvic pain affects 15% of women, resulting in considerable psychological, physical and economic burden and is difficult to treat. Tenderness or hypertonicity of the pelvic floor muscles can be a hyperalgesic muscular response in women with chronic pelvic pain. Pelvic floor hypertonicity is not routinely evaluated by physicians and is therefore likely underdiagnosed. This form of myofascial pain can represent a primary problem or a secondary adaptation to an acute or chronic injury to one or more of the musculoskeletal
components within the pelvic floor and surrounding structures. Chronic pelvic diseases such as endometriosis or interstitial cystitis can cause persistent hypertonic pelvic floorduring or long after treatment for the disease and are often associated with sensitization of the central nervous system. Because of the deep location of these muscles and the proximity of many visceral, neural and vascular structures, patients often cannot identify the source of their problem as musculoskeletal and present with a myriad of other symptoms, ranging fromdyspareunia to slow urinary stream, constipation and vaginal pressure.
Pelvic pain is a common disorder in women, causing significant morbidity. Often the aetiology is not clear as it results from a complex interaction between neurologic, musculoskeletal and endocrine systems that are further influenced by behavioural and psychological factors. Tenderness or hypertonicity of the pelvic floor muscles can be a hyperalgesic muscular response in women with chronic pelvic pain. Pelvic floor hypertonicity is not routinely evaluated by physicians and is therefore likely underdiagnosed. This form of myofascial pain can represent a primary problem or a secondary adaptation to an acute or chronic injury to one or more of the musculoskeletal components within the pelvic floor and surrounding structures. Chronic pelvic diseases such as endometriosis or interstitial cystitis can cause persistent hypertonic pelvic floor during or long after treatment for the disease and are often associated with sensitization of the central nervous system. Because of the deep location of these muscles and the proximity of many visceral, neural and vascular structures, patients often cannot identify the source of their problem as musculoskeletal and present with a myriad of other symptoms, ranging from dyspareunia to slow urinary stream, constipation and vaginal pressure. Injecting botulinum toxin type A (Botox) into hypertonic pelvic floor muscles may aid the relaxation of pelvic floor musculature and thereby relieve the pain and enable effective pelvic floor rehabilitation.
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 perineal) muscles. The deep pelvic floor muscles consist of pubococcygeus, iliococcygeus, 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, a 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), iliococcygeus, puborectalis and pubococcygeus and they 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 into the pelvic floor muscles, botulinum toxin can reduce 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 Acetylcholine (Ach) to cause muscle paralysis. BoNT-A inhibits ACh vesicle release in 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. Digital palpation is used for injecting most of the pelvic floor muscles and a thorough knowledge of anatomy is essential for performing this procedure. Ultrasound can be used for infiltration of some of the pelvic floor muscles like the obturator internus and the piriformis muscle.
The muscles that are commonly targeted include puborectalis coccygeus and the iliococcygeus, which together form the levator ani muscle/complex. Other muscles that can be targeted include coccygeus, piriformis, obturator internus and deep and superficial transverse perineal muscles. Superficial muscles including the bulbocavernosus and the ischiocavernosus may also be targeted if these muscles are tender to palpate. A total of 100 to 300 units of botox is injected into these muscles to reduce the hypertonicity. Botulinum toxin has a temporary effect, so repeat injections may be needed.
Botox injections can also be performed into the vestibular area for patients experiencing pain specifically in the vestibule.
Nesbitt-Hawes et al reported that clinical outcomes for single and subsequent Botox injections for recurrent pelvic pain are similar. In the subsequent injection, there is a cumulative effect with lower vaginal and maximal contraction pressures. Long-term treatment with Botox is generally tolerable and efficient; nevertheless, following an initial positive therapeutic effect, symptoms may fail to respond to upcoming treatments. Attributing factors considered for secondary nonresponse may include the development of neutralizing antibodies, missed injection of the target muscles, disease progression, and architectural changes following repeated injection. There is limited knowledge on the long-term implications, so further studies are required. Women who have benefitted from a single Botox injection can be informed that, if symptoms reoccur, repeated injections can be expected to be equally efficacious.
Injections are generally avoided in patients with systemic infection or skin infection over the 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 instability, history of reaction to the toxin, pregnancy and lactating females, and infection at the injection site.
Side effects are rare and include pain at the injection site, hematoma, and infection. The prevalence of side effects is similar to traditional trigger point injection therapy when used for myofascial pain. Adverse events associated with the neuromuscular effects of Botox have been rare and are dose-dependent. There can be mild injection pain and local oedema, erythema, transient numbness, headache, malaise or mild nausea. Post-procedural pain flare-up can occur in some patients, though this is rare with Botox injections and more common with steroid injections. Faecal incontinence occurs in less than 5% of patients after perianal injections of Botox and is also dose-related.