Commentary
c pain
Use of botulinum toxin for chronic pelvic pain “It has been suggested that up to 85% of women with chronic pelvic pain have dysfunction of the musculoskeletal system...” First draft submitted: 1 February 2016; Accepted for publication: 3 February 2016; Published online: 10 June 2016 Keywords: botulinum toxin • levator ani spasm • pelvic pain • trigger points
Chronic pelvic pain (CPP) is a significant healthcare problem with estimated prevalence of 2.1–24% of the female population worldwide, depending on the definition [1] . It is defined as continuous or recurrent pain in the lower abdomen or the pelvis lasting at least 6 months, not related to pregnancy, and sufficiently severe to interfere with the habitual activities of the patient. The etiology of pelvic pain is poorly understood and it is often the result of a complex interaction between the gastrointestinal, urinary, gynecologic, musculoskeletal, and neurologic and endocrine systems and is also influenced by psychological and sociocultural factors [2] . The social, psychological and economic impact of CPP is high. Compared with women who have no pelvic pain, women with any type of pelvic pain were more likely to report having some form of sexual difficulty for at least a month during the previous 12 months [3] . Estimated direct medical costs for outpatient visits for chronic pelvic pain for the US population of women aged 18–50 years are US$881.5 million per year. This medical cost is compounded by the economic cost to the women as reported in a study of 548 employed respondents, 15% reported time lost from paid work and 45% reported reduced work productivity [4] . It has been suggested that up to 85% of women with CPP have dysfunction of the musculoskeletal system, including postural changes, as well as changes in the pelvic muscles, such as spasm of the levator ani or obtu-
10.2217/whe-2016-0007 © 2016 Future Medicine Ltd
rator internus muscle [5] . This has recently become easier to classify with the development of the FIGO prolapse assessment scoring system [6] . Botulinum toxin has been successfully used to treat chronic pelvic pain – painful bladder syndrome, detrusor overactivity, vulvodynia, pelvic floor muscle spasm, anismus and chronic constipation. In this commentary we will limit our discussion for the use of botulinum toxin in the treatment of chronic pelvic pain due to pelvic floor muscle spasm (short pelvic floor syndrome) [7] . Trigger points are described as discrete, nodular, focal, hyperirritable areas, usually less than 1 cm in circumference, located in a taut band of skeletal muscle from which impulses travel to the central nervous system, giving rise to pain at the same location or referred to another area [8] . The muscles commonly involved with chronic pelvic pain are the pubococcygeus, iliococcygeus, ischiococcygeus, piriformis, obturator internus and deep and superficial transverse perinei mucles. Botulinum toxin is a potent neurotoxin produced by bacteria Clostridium Botulinum. There are seven different serotypes of Botulinum toxin. Botulinum toxin type A and type B have been injected in various spastic disorders, dystonia, extraocular muscles and for reducing facial wrinkles. In 2013, US FDA approved use of onabotulinumtoxin A for overactive bladder refractory to treatment with anticholinergics. The toxin has been researched widely for its safety and efficacy
Womens Health (2016) 12(3), 293–296
Bhawana Purwar Department of Urogynaecology, St Mary’s Hospital, 4th Floor, Mary Stanford Building, London, W21NY, UK
Vik Khullar Author for correspondence: Department of Urogynaecology, St Mary’s Hospital, 4th Floor, Mary Stanford Building, London, W21NY, UK [email protected]
part of
ISSN 1745-5057
293
Commentary Purwar & Khullar in other areas but the use of botox for gynecological indications is limited and still off-licence. To understand the use of botox in pain syndromes it is important to understand the mechanism of pain with muscle spasm/myofascial trigger points and mode of action of botox. The main factor in generating pain appears to be ischemia due to compression of the muscle’s blood vessels in cases of muscle spasm. Ischemia leads to the release of bradykinin and sensitization or excitation of nociceptors. Similarly, in a hyperactive muscle nerve compression can occur which leads to pain. Botulinum toxin can relax hyperactive muscle and the pain due to compressions of muscles and nerves. Myofascial trigger points start with a muscle lesion (e.g., overload) that leads to an excessive release of acetylcholine (ACh) into the cleft of the neuro-muscular junction. Botulinum toxin (BoNT) exerts its action by inhibiting the exocytosis of ACh in cholinergic nerve endings. BoNT cleaves proteins (e.g., SNAP-25 or VAMP) that are necessary for the docking of the ACh vesicle to the presynaptic membrane. Without docking, no ACh can be released into the synaptic cleft and the innervated structure is paralyzed [9] .
“Vaginal examination is key to the diagnosis...” Release of muscle tightness (paralysis) due to taut band will improve blood circulation and break the vicious cycle of spasm and pain. Other suggested mechanism is direct analgesic effect of BoNT as few patients report alleviation of pain before muscle relaxing effects of BoNT has set in [9] . When BoNT is injected into a striated muscle, paresis occurs after 2–5 days and lasts for 2–3 months before it gradually starts to wear off. When antibodies against BoNT are formed, the duration of action and the extent of the maximal therapeutic effect are usually reduced after few BoNT applications (partial therapy failure) before complete therapy failure occurs. There does seem to dose effect for BoNT as well [10] . Use of botulinum toxin for different musculoskeletal conditions has been described since 1990s but Brin and Vapnek first described the use of BoNT for vaginismus in 1997 [11] . Since then botox has increasingly been used for pelvic floor muscle spasm but there is still paucity of robust data for its use. Vaginal examination is key to the diagnosis and taut muscles are easily palpable and usually sufficient to make the diagnosis of pelvic floor spasm on vaginal examination. Electromyography (EMG) and perineometry may be used to aid diagnosis. Similarly ultrasound and EMG have been used for better recognition of trigger points for injections but there is limited use of diagnostic tools in current studies.
294
Womens Health (2016) 12(3)
Jarvis et al. carried out a prospective cohort study using forty units of BoNT at three different dilutions: 10; 20; and 100 IU/ml in 12 women and median visual analog scale scores were significantly improved for dyspareunia and dysmenorrhea, with nonsignificant reductions in nonmenstrual pelvic pain and dyschezia. Quality of life scores (EQ-5D and SF-12) were improved from baseline at week 12, but did not reach statistical significance. Sexual activity scores were markedly improved, with a significant reduction in discomfort (4.8 vs 2.2; p = 0.02) and improvement in habit (0.2 vs 1.9; p = 0.03). These results were not influenced by dilution [12] . Abbott et al. recruited women who presented with chronic pelvic pain of more than 2 years duration and evidence of pelvic floor muscle spasm in a double-blinded, randomized, placebo-controlled trial [13] . In total, 30 women had 80 units of botulinum toxin type A injected into the pelvic floor muscles, and 30 women received saline. Vaginal manometry was performed preoperatively. There was significant change from baseline in the botulinum toxin type A group for dyspareunia (visual analog scale [VAS] score 66 vs 12; p
c pain
Use of botulinum toxin for chronic pelvic pain “It has been suggested that up to 85% of women with chronic pelvic pain have dysfunction of the musculoskeletal system...” First draft submitted: 1 February 2016; Accepted for publication: 3 February 2016; Published online: 10 June 2016 Keywords: botulinum toxin • levator ani spasm • pelvic pain • trigger points
Chronic pelvic pain (CPP) is a significant healthcare problem with estimated prevalence of 2.1–24% of the female population worldwide, depending on the definition [1] . It is defined as continuous or recurrent pain in the lower abdomen or the pelvis lasting at least 6 months, not related to pregnancy, and sufficiently severe to interfere with the habitual activities of the patient. The etiology of pelvic pain is poorly understood and it is often the result of a complex interaction between the gastrointestinal, urinary, gynecologic, musculoskeletal, and neurologic and endocrine systems and is also influenced by psychological and sociocultural factors [2] . The social, psychological and economic impact of CPP is high. Compared with women who have no pelvic pain, women with any type of pelvic pain were more likely to report having some form of sexual difficulty for at least a month during the previous 12 months [3] . Estimated direct medical costs for outpatient visits for chronic pelvic pain for the US population of women aged 18–50 years are US$881.5 million per year. This medical cost is compounded by the economic cost to the women as reported in a study of 548 employed respondents, 15% reported time lost from paid work and 45% reported reduced work productivity [4] . It has been suggested that up to 85% of women with CPP have dysfunction of the musculoskeletal system, including postural changes, as well as changes in the pelvic muscles, such as spasm of the levator ani or obtu-
10.2217/whe-2016-0007 © 2016 Future Medicine Ltd
rator internus muscle [5] . This has recently become easier to classify with the development of the FIGO prolapse assessment scoring system [6] . Botulinum toxin has been successfully used to treat chronic pelvic pain – painful bladder syndrome, detrusor overactivity, vulvodynia, pelvic floor muscle spasm, anismus and chronic constipation. In this commentary we will limit our discussion for the use of botulinum toxin in the treatment of chronic pelvic pain due to pelvic floor muscle spasm (short pelvic floor syndrome) [7] . Trigger points are described as discrete, nodular, focal, hyperirritable areas, usually less than 1 cm in circumference, located in a taut band of skeletal muscle from which impulses travel to the central nervous system, giving rise to pain at the same location or referred to another area [8] . The muscles commonly involved with chronic pelvic pain are the pubococcygeus, iliococcygeus, ischiococcygeus, piriformis, obturator internus and deep and superficial transverse perinei mucles. Botulinum toxin is a potent neurotoxin produced by bacteria Clostridium Botulinum. There are seven different serotypes of Botulinum toxin. Botulinum toxin type A and type B have been injected in various spastic disorders, dystonia, extraocular muscles and for reducing facial wrinkles. In 2013, US FDA approved use of onabotulinumtoxin A for overactive bladder refractory to treatment with anticholinergics. The toxin has been researched widely for its safety and efficacy
Womens Health (2016) 12(3), 293–296
Bhawana Purwar Department of Urogynaecology, St Mary’s Hospital, 4th Floor, Mary Stanford Building, London, W21NY, UK
Vik Khullar Author for correspondence: Department of Urogynaecology, St Mary’s Hospital, 4th Floor, Mary Stanford Building, London, W21NY, UK [email protected]
part of
ISSN 1745-5057
293
Commentary Purwar & Khullar in other areas but the use of botox for gynecological indications is limited and still off-licence. To understand the use of botox in pain syndromes it is important to understand the mechanism of pain with muscle spasm/myofascial trigger points and mode of action of botox. The main factor in generating pain appears to be ischemia due to compression of the muscle’s blood vessels in cases of muscle spasm. Ischemia leads to the release of bradykinin and sensitization or excitation of nociceptors. Similarly, in a hyperactive muscle nerve compression can occur which leads to pain. Botulinum toxin can relax hyperactive muscle and the pain due to compressions of muscles and nerves. Myofascial trigger points start with a muscle lesion (e.g., overload) that leads to an excessive release of acetylcholine (ACh) into the cleft of the neuro-muscular junction. Botulinum toxin (BoNT) exerts its action by inhibiting the exocytosis of ACh in cholinergic nerve endings. BoNT cleaves proteins (e.g., SNAP-25 or VAMP) that are necessary for the docking of the ACh vesicle to the presynaptic membrane. Without docking, no ACh can be released into the synaptic cleft and the innervated structure is paralyzed [9] .
“Vaginal examination is key to the diagnosis...” Release of muscle tightness (paralysis) due to taut band will improve blood circulation and break the vicious cycle of spasm and pain. Other suggested mechanism is direct analgesic effect of BoNT as few patients report alleviation of pain before muscle relaxing effects of BoNT has set in [9] . When BoNT is injected into a striated muscle, paresis occurs after 2–5 days and lasts for 2–3 months before it gradually starts to wear off. When antibodies against BoNT are formed, the duration of action and the extent of the maximal therapeutic effect are usually reduced after few BoNT applications (partial therapy failure) before complete therapy failure occurs. There does seem to dose effect for BoNT as well [10] . Use of botulinum toxin for different musculoskeletal conditions has been described since 1990s but Brin and Vapnek first described the use of BoNT for vaginismus in 1997 [11] . Since then botox has increasingly been used for pelvic floor muscle spasm but there is still paucity of robust data for its use. Vaginal examination is key to the diagnosis and taut muscles are easily palpable and usually sufficient to make the diagnosis of pelvic floor spasm on vaginal examination. Electromyography (EMG) and perineometry may be used to aid diagnosis. Similarly ultrasound and EMG have been used for better recognition of trigger points for injections but there is limited use of diagnostic tools in current studies.
294
Womens Health (2016) 12(3)
Jarvis et al. carried out a prospective cohort study using forty units of BoNT at three different dilutions: 10; 20; and 100 IU/ml in 12 women and median visual analog scale scores were significantly improved for dyspareunia and dysmenorrhea, with nonsignificant reductions in nonmenstrual pelvic pain and dyschezia. Quality of life scores (EQ-5D and SF-12) were improved from baseline at week 12, but did not reach statistical significance. Sexual activity scores were markedly improved, with a significant reduction in discomfort (4.8 vs 2.2; p = 0.02) and improvement in habit (0.2 vs 1.9; p = 0.03). These results were not influenced by dilution [12] . Abbott et al. recruited women who presented with chronic pelvic pain of more than 2 years duration and evidence of pelvic floor muscle spasm in a double-blinded, randomized, placebo-controlled trial [13] . In total, 30 women had 80 units of botulinum toxin type A injected into the pelvic floor muscles, and 30 women received saline. Vaginal manometry was performed preoperatively. There was significant change from baseline in the botulinum toxin type A group for dyspareunia (visual analog scale [VAS] score 66 vs 12; p
