25-32 2009 SD 200-270g n 28 4 1 2 3 4 PE-50 4-5 0.25 60 C Key words acupuncture stimulation overactive bladder rat bladder irritation C C fiber Received November 17, 2008; Accepted January 9, 2009 I Overactive Bladder; OAB 1,2 40 12.4 810 70 22.5 33.3 3 629-0392 TEL: 0771-72-1181 FAX: 0771-72-0394 E-mail: hinokokoro@meiji-u.ac.jp Aδ silent C 4 Adenosine triphosphate; ATP C C 4
26 The Bulletin of Meiji University of Integrative Medicine Ach 63 74 5 30 6-8 1 9 1 C transient receptor potential vanilloid receptor-1; TRPV1 10 QOL II 1 19-4-1 Sprague-Dawley 28 200 270g 25 1 12 lights on at 7:00 and off at 19:00 2 50mg/kg 3cm PE-50 3 11 4-5 Yamashita Giken, Tokushima, Japan Brain Science Idia, USA 0.25 6ml/hr Nihon Kohden, Tokyo, Japan PowerLab/8s Chart Program V5.2.1 PowerLab/8s AD Insturuments Fig. 1 3 0.25 60 60 60 4 4 A n 8 B n 8 60 1 C n 8 1 D n 4 4 125mg/kg C 20mg/ml Sigma 10 ethanol 10 Tween 80 80 12 negative eye wipe test
Fig. 1. Schematic diagram of the experiment protocol. (A) Rats with bladder overactivity induced by acetic acid, (B) those treated with sacral acupuncture stimulation after induction of bladder overactivity by acetic acid (acupuncture stimulation rats), (C) non-acetic acid infusion rats and (D) those treated with sacral acupuncture stimulation after capsaicin-desensitization (capsaicin-desensitized rats). 1 27 7 One-way factorial ANOVA Tukey HSD test 5 Fig. 2. The analysis parameters on cystometrograms. intercontraction interval (ICI), basal pressure (BP), threshold pressure (TP) and micturition pressure (MP). 60 1 5 Fig. 2 min 1 cmh 2 O cmh 2 O cmh 2 O 6 0.3mm 30mm S3 1 2Hz III 1 Table 1 3 Fig. 3 Table 1 vs P 0.006 vs P 0.004 vs P 0.003 vs P 0.072 16.2 1.9min 19.3 1.8min vs
28 Table 1. Changes in cystometric parameters in the four group of rats. (A) Rats with bladder overactivity induced by acetic acid, (B) those treated with sacral acupuncture stimulation after induction of bladder overactivity by acetic acid (acupuncture stimulation rats), (C) non-acetic acid infusion rats and (D) those treated with sacral acupuncture stimulation after capsaicindesensitization (capsaicin-desensitized rats). The Bulletin of Meiji University of Integrative Medicine Cystometric parameters shown as mean SE. P<0.05, P<0.01: Before acetic acid infusion vs After acetic acid infusion. P<0.01: Before acetic acid infusion vs After saline infusion. Fig. 3. Typical cystometric findings in a rat with bladder overactivity induced by acetic acid (A), those in a rat treated with acupuncture stimulation after the induction of bladder overactivity by acetic acid before and after sacral acupuncture stimulation (B), those in a non-acetic acid infusion rat before and after sacral acupuncture stimulation (C) and those in a rat treated with sacral acupuncture stimulation with capsaicin-desensitization either before or after sacral stimulation (D). P 0.445 vs P 0.024 vs P 0.022 Table 1 vs P 0.212 vs P 0.141
C 2 C C Table 1 Fig. 3 C IV C 4 1 11 Aδ 14,15 C 9 C C 11 9 C TRPV1 C C TRPV1 4,16,17 12 13 C C Sato 18 19 29
30 The Bulletin of Meiji University of Integrative Medicine Tanaka 20 Wang 21 Locus ceruleus; LC Mitsui 22 Periaqueductal grey; PAG 6ml/hr 12ml/hr V 1 2 C 3 C 1. Abrams P, Cardozo L, Fall M, et al: The standardization of terminology of lower urinary tract function: Report from the standardization sub-committee of the International Continence Society. Neurourol Urodyn, 21: 167-178, 2002. 2. Dugan E, Cohen SJ, Bland DR, et al: The association of depressive symptoms and urinary incontinence among older adults. J Am Geriatr Soc, 48: 413-416, 2000. 3. 14: 266-277, 2003. 4. Zhang X, Igawa Y, Ishizuka O, et al: Effects of resiniferatoxin desensitization of capsaicinsensitive afferents on detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP in conscious rats. Naunyn Schmiedebergs Arch Pharmacol, 367: 473-479, 2003. 5. pp 30-51, 2005. 6. Yoshimura N, Chancellor MB: Current and future pharmacological treatment for overactive bladder. J Urol, 168: 1897-1913, 2002. 7. Andersson KE, Chapple C, Wein A: The basis for drug treatment of the overactive bladder. World J Urol, 19: 294-298, 2001. 8. Kakizaki H, de Groat WC: Role of spinal nitric oxide in the facilitation on the micturition reflex by bladder irritation. J Urol, 155: 355-360, 1996. 9. Chancellor MB, de Groat WC: Intravesical capsaicin and resiniferatoxin therapy, spicing up the ways to treat the overactive bladder. J Urol, 162: 3-11, 1999. 10. 86: 1514-1519, 1998. 11. 41: 29-39, 2007. 12. Birder LA, Kanai AJ, de Groat WC, et al: Vanilloid receptor expressioon suggests a sensory
role for urinary bladder epithelial cells. Proc 18. Sato A, Sato Y, Suzuki A: Mechanisms of the Natl Acad Sci USA, 98: 13396-13401, 2001. reflex inhibition of micturition contractions of 13. Szallasi A, Blumberg PM: Vanilloid (capsaicin) the urinary bladder elicited by acupuncturelike stimulation in anesthetized rats. Neurosci receptors and mechanisims. Pharmaclo Rev, 51: 159-212, 1999. Res, 15: 189-198, 1992. 14. Yoshimura N, de Groat WC: Neural control of 19. the lower urinary tract. Int J Urol, 4: 111-125, 29: 1997. 592-598, 1992. 15. de Groat WC, Kruse MN, Vizzard MA, et al: 20. Tanaka Y, Koyama Y, Jodo E, et al: Acupuncture to the sacral segment on the bladder activ- Modification of urinary bladder function after spinal cord injury. Adv Neurol, 72: 347-364, ity and electroencephalogram. Psychiatry Clin 1997. Neurosci, 56: 249-250, 2002. 16. Cheng CL, Ma CP, de Groat WC: Effects of capsaicin on micturition and associated reflexes in stimulation to the sacral segment affects state 21. Wang H, Tanaka Y, Seki H, et al: Acupuncture rats. Am J Physiol, 265: 132-138, 1993. of vigilance in rats. Neurosci Res, 57: 531-537, 17. Mitsui T, Kakizaki H, Matsuura S, et al: Afferent fibers of the hypogastric nerves are in- 22. Mitsui T, Kakizaki H, Matsuura S, et al: Chemi- 2007. volved in the facilitating effects of chemical cal bladder irritation provokes c-fos expression bladder irritation in rats. J Neurophysiol, 86: in the midbrain periaqueductal gray matter of 2276-2284, 2001. the rat. Brain Res, 967: 81-88, 2002. 31
32 The Effects of Sacral Acupuncture on Acetic Acid-induced Bladder Overactivity in Rats Kokoro Hino Department of Clinical Acupuncture and Moxibustion, Meiji University of Integrative Medicine The Bulletin of Meiji University of Integrative Medicine ABSTRACT Objectives: This study investigated the effects of sacral acupuncture on bladder overactivity induced by acetic acid in conscious rats. Methods: A total of 28 female Sprague-Dawley rats weighing 200 to 270 g were used in the present study. Animals were divided into 4 groups such as: A) Rats with bladder overactivity induced by acetic acid; B) those treated with sacral acupuncture stimulation after the induction of bladder overactivity by acetic acid (acupuncture stimulation rats); C) non-acetic acid infusion rats; and D) those treated with sacral acupuncture stimulation after capsaicin-desensitization (capsaicin-desensitized rats). Four or five days after polyethylene catheter implantation into the bladder, cystometry (CMGs) was performed without anesthesia. After obtaining base line CMG values with saline infusion, 0.25% acetic acid was infused constantly at the same infusion rate for 60 min. The following variables such as the intercontraction interval (ICI), basal pressure (BP), threshold pressure (TP) and micturition pressure (MP) were measured. Results: In control rats and acupuncture stimulation rats, ICI after induction of bladder overactivity by acetic acid was significantly decreased compared with the baseline, from 14.4±1.4 min to 8.2±1.3 min and from 15.7±1.7 min to 7.7±1.1 min, respectively. In acupuncture stimulation rats, ICI recovered from 7.7±1.1 min to 10.7±1.7 min by the sacral acupuncture stimulation. After recovery, ICI was not significantly shorter than that before acetic acid infusion. In non-acetic acid infusion rats, ICI after acupuncture increased from 16.2±1.9 min to 19.3±1.8 min, which did not reach a significant level. In capsaicin-desensitized rats, ICI did not decrease after induction bladder overactivity by acetic acid. Furthermore, there were no significant differences in ICI after sacral acupuncture stimulation. Conclusions: Sacral acupuncture might contribute to improving bladder overactivity induced by acetic acid through inhibition of capsaicin-sensitive C-fiber activation.