Caffeine enhances micturition through neuronal activation in micturition centers

Cho,Young‑Sam; Ko,Il‑Gyu; Kim,Sung‑Eun; Hwan,Lakkyong; Shin,Mal‑Soon; Kim,Chang‑Ju; Kim,Sang‑Hoon; Jin,Jun‑Jang; Chung,Jun‑Young; Kim,Khae‑Hawn

doi:10.3892/mmr.2014.2646

Caffeine enhances micturition through neuronal activation in micturition centers

Authors:
- Young‑Sam Cho
- Il‑Gyu Ko
- Sung‑Eun Kim
- Lakkyong Hwan
- Mal‑Soon Shin
- Chang‑Ju Kim
- Sang‑Hoon Kim
- Jun‑Jang Jin
- Jun‑Young Chung
- Khae‑Hawn Kim
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Affiliations: Department of Urology, Kangbuk Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 110‑746, Republic of Korea, Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea, Department of Physical Education, Graduate School of Education, Sangmyung University, Seoul 110‑743, Republic of Korea, Department of Physical Activity Design, College of Science, Hanseo University, Seosan 356‑706, Republic of Korea, Department of Anesthesiology and Pain Medicine, Gangdong Kyung Hee Hospital, College of Medicine, Kyung Hee University, Seoul 134‑727, Republic of Korea, Department of Urology, Gachon University Gil Medical Center, Incheon 405‑760, Republic of Korea
Published online on: October 15, 2014 https://doi.org/10.3892/mmr.2014.2646
Pages: 2931-2936

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Abstract

Caffeine may promote incontinence through its diuretic effect, particularly in individuals with underlying detrusor overactivity, in addition to increasing muscle contraction of the bladder smooth muscle. Caffeine may also affect bladder function via central micturition centers, including the medial preoptic area, ventrolateral periaqueductal gray, and pontine micturition center. However, the biochemical mechanisms of caffeine in central micturition centers affecting bladder function remain unclear. In the present study, the effects of caffeine on the central micturition reflex were investigated by measuring the degree of neuronal activation, and by quantifying nerve growth factor (NGF) expression in rats. Following caffeine administration for 14 days, a urodynamic study was performed to assess the changes to bladder function. Subsequently, immunohistochemical staining to identify the expression of c‑Fos and NGF in the central micturition areas was performed. Ingestion of caffeine increased bladder smooth muscle contraction pressure and time as determined by cystometry. Expression levels of c‑Fos and NGF in all central micturition areas were significantly increased following the administration of caffeine. The effects on contraction pressure and time were the most potent and expression levels of c‑Fos and NGF were greatest at the lowest dose of caffeine. These results suggest that caffeine facilitates bladder instability through enhancing neuronal activation in the central micturition areas.

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1	Anderson BL, Juliano LM and Schulkin J: Caffeine’s implications for women’s health and survey of obstetrician-gynecologists’ caffeine knowledge and assessment practices. J Womens Health (Larchmt). 18:1457–1466. 2009.
2	Jura YH, Townsend MK, Curhan GC, Resnick NM and Grodstein F: Caffeine intake, and the risk of stress, urgency and mixed urinary incontinence. J Urol. 185:1775–1780. 2011. View Article : Google Scholar : PubMed/NCBI
3	Lohsiriwat S, Hirunsai M and Chaiyaprasithi B: Effect of caffeine on bladder function in patients with overactive bladder symptoms. Urol Ann. 3:14–18. 2011. View Article : Google Scholar : PubMed/NCBI
4	Liao YM, Dougherty MC, Biemer PP, Liao CT, Palmer MH, Boyington AR and Connolly A: Factors related to lower urinary tract symptoms among a sample of employed women in Taipei. Neurourol Urodyn. 27:52–59. 2008. View Article : Google Scholar : PubMed/NCBI
5	Lee JG, Wein AJ and Levin RM: The effect of caffeine on the contractile response of the rabbit urinary bladder to field stimulation. Gen Pharmacol. 24:1007–1011. 1993. View Article : Google Scholar : PubMed/NCBI
6	Rickey LM, Sarkey S and DonCarlos LL: Estrogen-sensitive projections from the medial preoptic area to the dorsal pontine tegmentum, including Barrington’s nucleus, in the rat. Neurourol Urodyn. 27:440–445. 2008.
7	Blok BFM and Holstege G: Direct projections from the periaqueductal gray to the pontine micturition center (M-region). An anterograde and retrograde tracing study in the cat. Neurosci Lett. 166:93–96. 1994. View Article : Google Scholar
8	de Groat WC and Yoshimura N: Mechanisms underlying the recovery of lower urinary tract function following spinal cord injury. Prog Brain Res. 152:59–84. 2006.
9	Lachance MP, Marlowe C and Waddell WJ: Autoradiographic disposition of [1-methyl-14C]- and [2–14C]caffeine in mice. Toxicol Appl Pharmacol. 71:237–241. 1983.
10	Tanaka H, Nakazawa K, Arima M and Iwasaki S: Caffeine and its dimethylxanthines and fetal cerebral development in rat. Brain Dev. 6:355–361. 1984. View Article : Google Scholar : PubMed/NCBI
11	Pelligrino DA, Xu HL and Vetri F: Caffeine and the control of cerebral hemodynamics. J Alzheimers Dis. 20(Suppl 1): S51–S62. 2010.PubMed/NCBI
12	Seo JH, Kim TW, Kim CJ, Sung YH and Lee SJ: Treadmill exercise during pregnancy ameliorates post-traumatic stress disorder-induced anxiety-like responses in maternal rats. Mol Med Rep. 7:389–395. 2013.PubMed/NCBI
13	Dinis P, Charrua A, Avelino A and Cruz F: Intravesical resiniferatoxin decreases spinal c-fos expression and increases bladder volume to reflex micturition in rats with chronic inflamed urinary bladders. BJU Int. 94:153–157. 2004.
14	Kavia RB, Dasgupta R and Fowler CJ: Functional imaging and the central control of the bladder. J Comp Neurol. 493:27–32. 2005. View Article : Google Scholar : PubMed/NCBI
15	Steers WD and Tuttle JB: Mechanisms of Disease: the role of nerve growth factor in the pathophysiology of bladder disorders. Nat Clin Pract Urol. 3:101–110. 2006. View Article : Google Scholar : PubMed/NCBI
16	Lowe EM, Anand P, Terenghi G, Williams-Chestnut RE, Sinicropi DV and Osborne JL: Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis. Br J Urol. 79:572–577. 1997. View Article : Google Scholar
17	Kuo HC, Liu HT and Chancellor MB: Urinary nerve growth factor is a better biomarker than detrusor wall thickness for the assessment of overactive bladder with incontinence. Neurourol Urodyn. 29:482–487. 2010.PubMed/NCBI
18	Kim SE, Shin MS, Kim CJ, Park JH, Chung KJ, Jung H, Kim KH, Lee JH and Ko IG: Effects of tamsulosin on urinary bladder function and neuronal activity in the voiding centers of rats with cyclophosphamide-induced overactive bladder. Int Neurourol J. 16:13–22. 2012. View Article : Google Scholar
19	Creighton SM and Stanton SL: Caffeine: does it affect your bladder? Br J Urol. 66:613–614. 1990. View Article : Google Scholar : PubMed/NCBI
20	Arya LA, Myers DL and Jackson ND: Dietary caffeine intake and the risk for detrusor instability: a case-control study. Obstet Gynecol. 96:85–89. 2000. View Article : Google Scholar : PubMed/NCBI
21	Bortolotti A, Bernardini B, Colli E, Di Benedetto P, Giocoli Nacci G, Landoni M, Lavezzari M, Pagliarulo A, Salvatore S, von Heland M, Parazzini F and Artibani W: Prevalence and risk factors for urinary incontinence in Italy. Eur Urol. 37:30–35. 2000. View Article : Google Scholar : PubMed/NCBI
22	Tettamanti G, Altman D, Pedersen NL, Bellocco R, Milsom I and Iliadou AN: Effects of coffee and tea consumption on urinary incontinence in female twins. BJOG. 118:806–813. 2011. View Article : Google Scholar : PubMed/NCBI
23	Tomlinson BU, Dougherty MC, Pendergast JF, Boyington AR, Coffman MA and Pickens SM: Dietary caffeine, fluid intake and urinary incontinence in older rural women. Int Urogynecol J Pelvic Floor Dysfunct. 10:22–28. 1999. View Article : Google Scholar : PubMed/NCBI
24	Fowler CJ: Integrated control of lower urinary tract - clinical perspective. Br J Pharmacol. 147(Suppl 2): S14–S24. 2006. View Article : Google Scholar : PubMed/NCBI
25	Jun JH, Kang HJ, Jin MH, Lee HY, Im YJ, Jung HJ and Han SW: Function of the cold receptor (TRPM8) associated with voiding dysfunction in bladder outlet obstruction in rats. Int Neurourol J. 6:69–76. 2012. View Article : Google Scholar : PubMed/NCBI
26	Kershen R, Mann-Gow T, Yared J, Stromberg I and Zvara P: Caffeine ingestion causes detrusor overactivity and afferent nerve excitation in mice. J Urol. 188:1986–1992. 2012. View Article : Google Scholar : PubMed/NCBI
27	Blok BFM and Holstege G: The pontine micturition center in rat receives direct lumbosacral input. An ultrastructural study. Neurosci Lett. 282:29–32. 2000. View Article : Google Scholar : PubMed/NCBI
28	Sakakibara R, Hattori T, Yasuda K, Yamanishi T, Tojo M and Mori M: Micturitional disturbance in Wernicke’s encephalopathy. Neurourol Urodyn. 16:111–115. 1997.PubMed/NCBI
29	Dragunow M and Faull R: The use of c-fos as a metabolic marker in neuronal pathway tracing. J Neurosci Methods. 29:261–265. 1989. View Article : Google Scholar : PubMed/NCBI
30	Gaytan SP and Pasaro R: Neonatal caffeine treatment up-regulates adenosine receptors in brainstem and hypothalamic cardio-respiratory related nuclei of rat pups. Exp Neurol. 237:247–259. 2012. View Article : Google Scholar : PubMed/NCBI
31	Bon K, Lantéri-Minet M, de Pommery J, Michiels JF and Menétrey D: Cyclophosphamide cystitis as a model of visceral pain in rats. A survey of hindbrain structures involved in visceroception and nociception using the expression of c-Fos and Krox-24 proteins. Exp Brain Res. 108:404–416. 1996. View Article : Google Scholar : PubMed/NCBI
32	Svenningsson P, Nomikos GG and Fredholm BB: The stimulatory action and the development of tolerance to caffeine is associated with alterations in gene expression in specific brain regions. J Neurosci. 19:4011–4022. 1999.PubMed/NCBI
33	Okragly AJ, Niles AL, Saban R, Schmidt D, Hoffman RL, Warner TF, Moon TD, Uehling DT and Haak-Frendscho M: Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients. J Urol. 161:438–442. 1999. View Article : Google Scholar
34	Furuta A, Kita M, Suzuki Y, Egawa S, Chancellor MB, de Groat WC and Yoshimura N: Association of overactive bladder and stress urinary incontinence in rats with pudendal nerve ligation injury. Am J Physiol Regul Integr Comp Physiol. 294:R1510–R1516. 2008. View Article : Google Scholar : PubMed/NCBI
35	Yi CR, Wei ZQ, Deng XL, Sun ZY, Li XR and Tian CG: Effects of coffee and caffeine on bladder dysfunction in streptozotocin-induced diabetic rats. Acta Pharmacol Sin. 27:1037–1043. 2006. View Article : Google Scholar : PubMed/NCBI
36	Toledo-Aral JJ, Brehm P, Halegoua S and Mandel G: A single pulse of nerve growth factor triggers long-term neuronal excitability through sodium channel gene induction. Neuron. 14:607–611. 1995. View Article : Google Scholar
37	Jia Z, Bei J, Rodat-Despoix L, Liu B, Jia Q, Delmas P and Zhang H: NGF inhibits M/KCNQ currents and selectively alters neuronal excitability in subsets of sympathetic neurons depending on their M/KCNQ current background. J Gen Physiol. 131:575–587. 2008. View Article : Google Scholar : PubMed/NCBI