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Therapeutic effects of antidepressants and Kampo medicines on chronic pelvic pain in women
International Congress Series 1287 (2006) 329 – 333
www.ics-elsevier.com
Therapeutic effects of antidepressants and Kampo medicines on chronic pelvic pain in women Mina Morimura a,*, Kouzo Hirai b, Chiho Yoshimura a, Tamaki Matsumoto c, Kei Tsumura a, Osamu Ishiko d a
d
Department of Graduate Medical Education and General Practice, Osaka City University Graduate School of Medicine, Osaka, Japan b Minami-Morimachi Ladies’ Clinic, Osaka, Japan c Department of Health Science, International Buddhist University, Osaka, Japan Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka, Japan
Abstract. Chronic pelvic pain is a common and significant disorder among women. However, its etiology is not clear, and effective treatments remain inconclusive. The present study was designed to investigate the efficacy of antidepressants and Kampo medicines, which have been applied for other pain disorders, to treat chronic pelvic pain in women. Twenty-nine gynecological outpatients received pharmacological treatments. None of the patients had clear organic abnormalities that could explain their pain, nor did they have menstruation-related disorders. After considering severity of pain and clinical and psychosocial conditions for each patient, the medication and its administration was determined. Pain severity decreased in patients with antidepressants, which have been demonstrated to alleviate general chronic pain modulating through the descending pain inhibitory system. Kampo medicines such as Shuji-bushi, Sanyaku and Takusha also mitigated pain in patients. Our findings suggest that chronic pelvic pain, especially vulval pain, is difficult to treat, but administration of appropriate medication is effective and adjuvant analgesics could eliminate the symptoms. The present study further implies that a suitable pharmacological therapy, together with a psychological one–if necessary–is crucial in effectively treating chronic pelvic pain, which might induce depression and, ultimately, deteriorate quality of life. D 2005 Elsevier B.V. All rights reserved. Keywords: Chronic pelvic pain; Antidepressant; Selective serotonin norepinephrine reuptake inhibitors; Kampo medicine; Descending pain inhibitory system; Gynecology
* Corresponding author. Tel.: +81 6 6645 3797; fax: +81 6 6 6645 3796. E-mail address: [email protected] (M. Morimura). 0531-5131/ D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2005.10.003
330
M. Morimura et al. / International Congress Series 1287 (2006) 329–333
1. Introduction In general, symptoms of chronic pain are diverse and differ greatly among individuals. Thus, medical doctors often have a difficult time diagnosing and providing appropriate treatment. In the field of gynecology, a wide variety of chronic pain diseases also exist. Doctors often use the term bnonexistence of appreciable diseasesQ when presented with chronic pain without any organic disease or known cause. Therefore, quite a lot of patients with agonizing chronic pain visit one doctor after another. Gynecological pelvic pain has been defined as bnonmenstrual pelvic pain lasting six or more months that is severe enough to cause functional disability or requires medical or surgical treatmentQ [1–3]. Compared with other countries, Japan has fewer research reports regarding such cases. However, some attention has been paid to chronic pelvic pain in women, and its appropriate treatments have been investigated. As general treatments for chronic pain, anti-inflammatory painkillers or opioids have been applied, but it has been reported that their long-term administration could cause side effects. Psychotherapy, including counseling, might be effective; however, such consultation takes a much longer time. In contrast, adjuvant analgesics have been reported to cause less adverse effects and facilitate recovery from chronic pain. Especially in the gynecological field, herbal medicine or Kampo, as well as hormone replacement therapy and ointments, have been used quite often. In addition, treatment with antidepressants to alleviate the pain has recently attracted attention. Accordingly, the present study was designed to investigate the efficacy of pharmacological therapy including antidepressants and Kampo medicines on women with chronic pain disorders including pelvic pain. 2. Materials and methods Twenty-nine subjects, who were patients at our gynecological outpatient clinic from June 2001 to June 2005, participated in the study. Patients’ ages ranged from 17 to 86 years. All patients suffered from the chronic pain lasting for at least 6 months. None of them had any clear organic abnormality that could explain the pain they reported, nor did they have any menstrual-related disorders. Of the 29 patients, 20 suffered from chronic pelvic pain including abdominal and vulval pain, and 9 had other chronic pain including headache and fibromyalgia. After considering severity of pain and clinical and psychosocial conditions for each patient, the doctor in charge determined the patient’s pharmacological treatment. 3. Results We had various kinds of cases, and effects of treatments varied among patients. We used mainly Kampo to treat vulval pain, and Gosha-jinki-gan was more effective than other Kampo medicines. Enterokinetic agents had a beneficial effect on treating lower abdominal pain including irritable bowel syndrome. Selective serotonin norepinephrine reuptake inhibitors were effective in alleviating head or muscle pain. Two typical cases follow with the results of the medical treatment summarized in Figs. 1 and 2, respectively. A 59-year-old woman, who worked part time, visited our clinic complaining of external genital pain. She had been receiving treatments of hormone replacement and painkillers, which did not work. She was somewhat depressed because of her refractory condition. We suggested starting Kampo therapy under informed consent. She was happy to receive, for the first time, an explanation
M. Morimura et al. / International Congress Series 1287 (2006) 329–333
331
Fig. 1. Pharmacological effects of Gosha-jinki-gan and Milnacipran on a 59-year-old patient.
about the disease rather than being told she had an unknown mental problem. The symptoms began subsiding during treatment with several kinds of Kampo, estrogen, and external medication. She gradually accepted the conditions of the disease and agreed to the treatment with an antidepressant. Soon after starting Milnacipran and Gosha-jinki-gan, she recovered from the symptoms, with VAS going down from 8.5 to 1.9 cm. The medical record of the second case follows. A 52-year-old housewife suffered from severe arthritic and muscle pain from her upper body to her pelvis. She also experienced menopausal symptoms and incontinence. As to her personal situation, her husband unexpectedly lost his job to corporate restructuring, which might be associated with stress exacerbating her condition. Soon after the administration of Gosha-jinki-gan, her arthritic and muscle pain were alleviated. Estrogen replacement therapy was also conducted to treat menopausal symptoms.
4. Discussion Weak pain is not generally recognized in humans because the sensory transmission is controlled via the descending noradrenergic and/or serotonergic pain inhibitory system.
Fig. 2. Pharmacological effects of Gosha-jinki-gan on a 52-year-old patient.
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M. Morimura et al. / International Congress Series 1287 (2006) 329–333
Chronic pain, however, might cause a disruption in the descending pain inhibitory system, which normally prevents the transmission of pain sensation (Fig. 3) [4]. Recently, it has been reported that antidepressants might accelerate the effect of inhibitory mechanisms through modulating neurotransmitters such as noradrenalin and serotonin to alleviate chronic pain [5]. In Japan, Kampo medicine has been applied as a treatment for chronic abnormal sensation. This includes Gosha-jinkigan, used to treat diabetic neuropathy or lower-limb pain caused by side effects of anticancer drugs. According to previous research, Shujibushi facilitates the release of dynorphin, which stimulates the intramedullary-eˆ-opioid receptor. This stimulation activates the descending pain modulatory system, inducing analgesic action [6,7]. Sanyaku or Takusha increases the production of nitric oxide, which enhances pain relief and improves blood circulation, resulting in alleviation of chronic pain and its associated symptoms [8]. The present study provides intriguing and novel information regarding the efficacy of antidepressants and Kampo medicines for women with chronic pain disorders. Our data indicate that for treating chronic pain disorder, administration of appropriate medication could eliminate symptoms effectively. For instance, as well as antidepressants, Kampo, such as Shuji-bushi, which activates the descending pain modulatory system, and Sanyaku or Takusha, which enhances blood circulation by the action of nitric oxide, contribute to eliminating chronic pelvic pain. In addition, adjuvant analgesics could also eliminate symptoms of vulval pain associated with chronic pelvic pain, which is especially difficult to treat. The majority of patients with chronic pain feel anxiety if they cannot receive a convincing explanation regarding their symptoms from their primary doctor. Therefore, it is of importance to listen carefully to patients’ complaints and to describe a patient’s medical condition as clearly as possible. Previous clinical studies have reported that chronic pain disorder may cause depression and markedly worsen the quality of life of the patient [9]. In addition, women with chronic pelvic pain could have a higher incidence of
Fig. 3. Central neural modulation of chronic pain.
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333
sexual abuse than women without the pain [10,11]. Taken together, the present investigation further implies that a suitable pharmacological therapy accompanying a psychological one–if necessary–could be crucial to treating chronic pelvic pain effectively. References [1] F.M. Howard, The role of laparoscopy in chronic pelvic pain: promise and pitfalls, Obstet. Gynecol. Surv. 48 (1993) 357 – 387. [2] F.M. Howard, Chronic pelvic pain, Obstet. Gynecol. 101 (2003) 594 – 611. [3] S.D. Mathias, et al., Chronic pelvic pain: prevalence, health-related quality of life, and economic correlates, Obstet. Gynecol. 87 (1996) 321 – 327. [4] T. Tsubokawa, et al., Thalamic relay nucleus stimulation for relief of intractable pain. Clinical results and beta-endorphin immunoreactivity in the cerebrospinal fluid, Pain 18 (1984) 115 – 126. [5] M. Stephen, The effect of antidepressant treatment on chronic back pain, Arch. Intern. Med. 162 (2002) 19 – 24. [6] Y. Omiya, et al., Analgesia-producing mechanism of processed aconiti tuber: role of dynorphin, an endogenous n-opioid ligand, in the rodent spinal cord, Jpn. J. Pharmacol. 79 (1999) 295 – 301. [7] Y. Suzuki, et al., Kamei: antinociceptive effect of Gosha-jinki-gan, a Kampo medicine, in streptozotocininduced diabetic mice, Jpn. J. Pharmacol. 79 (1999) 169 – 175. [8] Y. Suzuki, et al., Kamei: effect of Gosha-jinki-gan, a Kampo medicine, on enhanced platelet aggregation in streptozotocin-induced diabetic rats, Jpn. J. Pharmacol. (1998) 78 – 87. [9] B.L. Dinoff, S.M. Meade-Pruitt, D.M. Doleys, Mental health care providers: resource rather than last resort in patients with chronic pelvic pain, Clin. Obstet. Gynecol. 46 (4) (2003) 804 – 810. [10] R. Bodden-Heidrich, et al., Chronic pelvic pain syndrome (CPPS) and chronic vulvar pain syndrome (CVPS): evaluation of psychosomatic aspects, J. Psychosom. Obstet. Gynaecol. 20 (1999) 145 – 151. [11] B.J. Collett, et al., A comparative study of women with chronic pelvic pain, chronic nonpelvic pain and those with no history of pain attending general practitioners, Br. J. Obstet. Gynaecol. 105 (1998) 87 – 92.
www.ics-elsevier.com
Therapeutic effects of antidepressants and Kampo medicines on chronic pelvic pain in women Mina Morimura a,*, Kouzo Hirai b, Chiho Yoshimura a, Tamaki Matsumoto c, Kei Tsumura a, Osamu Ishiko d a
d
Department of Graduate Medical Education and General Practice, Osaka City University Graduate School of Medicine, Osaka, Japan b Minami-Morimachi Ladies’ Clinic, Osaka, Japan c Department of Health Science, International Buddhist University, Osaka, Japan Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka, Japan
Abstract. Chronic pelvic pain is a common and significant disorder among women. However, its etiology is not clear, and effective treatments remain inconclusive. The present study was designed to investigate the efficacy of antidepressants and Kampo medicines, which have been applied for other pain disorders, to treat chronic pelvic pain in women. Twenty-nine gynecological outpatients received pharmacological treatments. None of the patients had clear organic abnormalities that could explain their pain, nor did they have menstruation-related disorders. After considering severity of pain and clinical and psychosocial conditions for each patient, the medication and its administration was determined. Pain severity decreased in patients with antidepressants, which have been demonstrated to alleviate general chronic pain modulating through the descending pain inhibitory system. Kampo medicines such as Shuji-bushi, Sanyaku and Takusha also mitigated pain in patients. Our findings suggest that chronic pelvic pain, especially vulval pain, is difficult to treat, but administration of appropriate medication is effective and adjuvant analgesics could eliminate the symptoms. The present study further implies that a suitable pharmacological therapy, together with a psychological one–if necessary–is crucial in effectively treating chronic pelvic pain, which might induce depression and, ultimately, deteriorate quality of life. D 2005 Elsevier B.V. All rights reserved. Keywords: Chronic pelvic pain; Antidepressant; Selective serotonin norepinephrine reuptake inhibitors; Kampo medicine; Descending pain inhibitory system; Gynecology
* Corresponding author. Tel.: +81 6 6645 3797; fax: +81 6 6 6645 3796. E-mail address: [email protected] (M. Morimura). 0531-5131/ D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2005.10.003
330
M. Morimura et al. / International Congress Series 1287 (2006) 329–333
1. Introduction In general, symptoms of chronic pain are diverse and differ greatly among individuals. Thus, medical doctors often have a difficult time diagnosing and providing appropriate treatment. In the field of gynecology, a wide variety of chronic pain diseases also exist. Doctors often use the term bnonexistence of appreciable diseasesQ when presented with chronic pain without any organic disease or known cause. Therefore, quite a lot of patients with agonizing chronic pain visit one doctor after another. Gynecological pelvic pain has been defined as bnonmenstrual pelvic pain lasting six or more months that is severe enough to cause functional disability or requires medical or surgical treatmentQ [1–3]. Compared with other countries, Japan has fewer research reports regarding such cases. However, some attention has been paid to chronic pelvic pain in women, and its appropriate treatments have been investigated. As general treatments for chronic pain, anti-inflammatory painkillers or opioids have been applied, but it has been reported that their long-term administration could cause side effects. Psychotherapy, including counseling, might be effective; however, such consultation takes a much longer time. In contrast, adjuvant analgesics have been reported to cause less adverse effects and facilitate recovery from chronic pain. Especially in the gynecological field, herbal medicine or Kampo, as well as hormone replacement therapy and ointments, have been used quite often. In addition, treatment with antidepressants to alleviate the pain has recently attracted attention. Accordingly, the present study was designed to investigate the efficacy of pharmacological therapy including antidepressants and Kampo medicines on women with chronic pain disorders including pelvic pain. 2. Materials and methods Twenty-nine subjects, who were patients at our gynecological outpatient clinic from June 2001 to June 2005, participated in the study. Patients’ ages ranged from 17 to 86 years. All patients suffered from the chronic pain lasting for at least 6 months. None of them had any clear organic abnormality that could explain the pain they reported, nor did they have any menstrual-related disorders. Of the 29 patients, 20 suffered from chronic pelvic pain including abdominal and vulval pain, and 9 had other chronic pain including headache and fibromyalgia. After considering severity of pain and clinical and psychosocial conditions for each patient, the doctor in charge determined the patient’s pharmacological treatment. 3. Results We had various kinds of cases, and effects of treatments varied among patients. We used mainly Kampo to treat vulval pain, and Gosha-jinki-gan was more effective than other Kampo medicines. Enterokinetic agents had a beneficial effect on treating lower abdominal pain including irritable bowel syndrome. Selective serotonin norepinephrine reuptake inhibitors were effective in alleviating head or muscle pain. Two typical cases follow with the results of the medical treatment summarized in Figs. 1 and 2, respectively. A 59-year-old woman, who worked part time, visited our clinic complaining of external genital pain. She had been receiving treatments of hormone replacement and painkillers, which did not work. She was somewhat depressed because of her refractory condition. We suggested starting Kampo therapy under informed consent. She was happy to receive, for the first time, an explanation
M. Morimura et al. / International Congress Series 1287 (2006) 329–333
331
Fig. 1. Pharmacological effects of Gosha-jinki-gan and Milnacipran on a 59-year-old patient.
about the disease rather than being told she had an unknown mental problem. The symptoms began subsiding during treatment with several kinds of Kampo, estrogen, and external medication. She gradually accepted the conditions of the disease and agreed to the treatment with an antidepressant. Soon after starting Milnacipran and Gosha-jinki-gan, she recovered from the symptoms, with VAS going down from 8.5 to 1.9 cm. The medical record of the second case follows. A 52-year-old housewife suffered from severe arthritic and muscle pain from her upper body to her pelvis. She also experienced menopausal symptoms and incontinence. As to her personal situation, her husband unexpectedly lost his job to corporate restructuring, which might be associated with stress exacerbating her condition. Soon after the administration of Gosha-jinki-gan, her arthritic and muscle pain were alleviated. Estrogen replacement therapy was also conducted to treat menopausal symptoms.
4. Discussion Weak pain is not generally recognized in humans because the sensory transmission is controlled via the descending noradrenergic and/or serotonergic pain inhibitory system.
Fig. 2. Pharmacological effects of Gosha-jinki-gan on a 52-year-old patient.
332
M. Morimura et al. / International Congress Series 1287 (2006) 329–333
Chronic pain, however, might cause a disruption in the descending pain inhibitory system, which normally prevents the transmission of pain sensation (Fig. 3) [4]. Recently, it has been reported that antidepressants might accelerate the effect of inhibitory mechanisms through modulating neurotransmitters such as noradrenalin and serotonin to alleviate chronic pain [5]. In Japan, Kampo medicine has been applied as a treatment for chronic abnormal sensation. This includes Gosha-jinkigan, used to treat diabetic neuropathy or lower-limb pain caused by side effects of anticancer drugs. According to previous research, Shujibushi facilitates the release of dynorphin, which stimulates the intramedullary-eˆ-opioid receptor. This stimulation activates the descending pain modulatory system, inducing analgesic action [6,7]. Sanyaku or Takusha increases the production of nitric oxide, which enhances pain relief and improves blood circulation, resulting in alleviation of chronic pain and its associated symptoms [8]. The present study provides intriguing and novel information regarding the efficacy of antidepressants and Kampo medicines for women with chronic pain disorders. Our data indicate that for treating chronic pain disorder, administration of appropriate medication could eliminate symptoms effectively. For instance, as well as antidepressants, Kampo, such as Shuji-bushi, which activates the descending pain modulatory system, and Sanyaku or Takusha, which enhances blood circulation by the action of nitric oxide, contribute to eliminating chronic pelvic pain. In addition, adjuvant analgesics could also eliminate symptoms of vulval pain associated with chronic pelvic pain, which is especially difficult to treat. The majority of patients with chronic pain feel anxiety if they cannot receive a convincing explanation regarding their symptoms from their primary doctor. Therefore, it is of importance to listen carefully to patients’ complaints and to describe a patient’s medical condition as clearly as possible. Previous clinical studies have reported that chronic pain disorder may cause depression and markedly worsen the quality of life of the patient [9]. In addition, women with chronic pelvic pain could have a higher incidence of
Fig. 3. Central neural modulation of chronic pain.
M. Morimura et al. / International Congress Series 1287 (2006) 329–333
333
sexual abuse than women without the pain [10,11]. Taken together, the present investigation further implies that a suitable pharmacological therapy accompanying a psychological one–if necessary–could be crucial to treating chronic pelvic pain effectively. References [1] F.M. Howard, The role of laparoscopy in chronic pelvic pain: promise and pitfalls, Obstet. Gynecol. Surv. 48 (1993) 357 – 387. [2] F.M. Howard, Chronic pelvic pain, Obstet. Gynecol. 101 (2003) 594 – 611. [3] S.D. Mathias, et al., Chronic pelvic pain: prevalence, health-related quality of life, and economic correlates, Obstet. Gynecol. 87 (1996) 321 – 327. [4] T. Tsubokawa, et al., Thalamic relay nucleus stimulation for relief of intractable pain. Clinical results and beta-endorphin immunoreactivity in the cerebrospinal fluid, Pain 18 (1984) 115 – 126. [5] M. Stephen, The effect of antidepressant treatment on chronic back pain, Arch. Intern. Med. 162 (2002) 19 – 24. [6] Y. Omiya, et al., Analgesia-producing mechanism of processed aconiti tuber: role of dynorphin, an endogenous n-opioid ligand, in the rodent spinal cord, Jpn. J. Pharmacol. 79 (1999) 295 – 301. [7] Y. Suzuki, et al., Kamei: antinociceptive effect of Gosha-jinki-gan, a Kampo medicine, in streptozotocininduced diabetic mice, Jpn. J. Pharmacol. 79 (1999) 169 – 175. [8] Y. Suzuki, et al., Kamei: effect of Gosha-jinki-gan, a Kampo medicine, on enhanced platelet aggregation in streptozotocin-induced diabetic rats, Jpn. J. Pharmacol. (1998) 78 – 87. [9] B.L. Dinoff, S.M. Meade-Pruitt, D.M. Doleys, Mental health care providers: resource rather than last resort in patients with chronic pelvic pain, Clin. Obstet. Gynecol. 46 (4) (2003) 804 – 810. [10] R. Bodden-Heidrich, et al., Chronic pelvic pain syndrome (CPPS) and chronic vulvar pain syndrome (CVPS): evaluation of psychosomatic aspects, J. Psychosom. Obstet. Gynaecol. 20 (1999) 145 – 151. [11] B.J. Collett, et al., A comparative study of women with chronic pelvic pain, chronic nonpelvic pain and those with no history of pain attending general practitioners, Br. J. Obstet. Gynaecol. 105 (1998) 87 – 92.