Advertisement

Current Urology Reports

, 20:54 | Cite as

Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms: What Is the Role and Significance of Inflammation?

  • Granville L. LloydEmail author
  • Jeffrey M. Marks
  • William A. Ricke
Benign Prostatic Hyperplasia (K McVary, Section Editor)
  • 64 Downloads
Part of the following topical collections:
  1. Topical Collection on Benign Prostatic Hyperplasia

Abstract

Purpose of Review

The purpose of this review is to summarize the role and significance of inflammation as a putative additional factor contributing to lower urinary tract symptoms and the progression of benign prostatic hyperplasia. We review (1) the histologic definition of prostatic inflammation and its prevalence, (2) the effects inflammation in the prostate including on risk of acute urinary retention, and (3) the effects of systemic inflammation on the prostate and on voiding.

Recent Findings

Inflammation is a highly prevalent finding in the prostate, both on a histological and biochemical level. Men with inflammation have higher IPSS scores and increased prostate size; however, these differences appear to be imperceptibly small. Men with inflammation do experience a significantly increased risk of developing acute urinary retention, an event that is associated with significant morbidity. Recently, attempts have been made to identify more specific biochemical markers of local inflammation, and to identify regional patterns of inflamed tissue within the prostate which may be associated with higher IPSS scores, accelerated progression, and AUR. The effects of systemic inflammatory states, most notably MetS, and their role in LUTS have also been examined.

Summary

Inflammation is a common finding in prostates of aging men, but its contribution to lower urinary tract symptoms and benign prostatic hyperplasia progression appears to be small when considered as a clinically relevant entity. Advances in the understanding of different forms of inflammation, and their impact when experienced in different locations within the prostate, may refine this knowledge. Systemic inflammation affects voiding, including in the absence of a prostate, but again significant effects of systemic inflammation on the prostate itself are also difficult to demonstrate. Prostatic inflammation is associated with a significantly increased risk of acute urinary retention.

Keywords

Prostatic inflammation Benign prostate hyperplasia Lower urinary tract symptoms Inflammation 

Notes

Funding information

This work was also supported by grants NIH U54 DK104310 and R01 ES01332 (WAR).

Compliance with Ethical Standards

Conflict of Interest

Granville L. Lloyd, Jeffrey M. Marks, and William A. Ricke each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Armitage JN, Sibanda N, Cathcart PJ, Emberton M, van der Meulen JHP. Mortality in men admitted to hospital with acute urinary retention: database analysis. BMJ. 2007;335:1199–202.CrossRefGoogle Scholar
  2. 2.
    Asplund R. Mortality in the elderly in relation to nocturnal micturition. BJU Int. 1999;84:297–301.CrossRefGoogle Scholar
  3. 3.
    Kaplan SA, Te AE, Pressler LB, Olsson CA. Transition zone index as a method of assessing benign prostatic hyperplasia: correlation with symptoms, urine flow and detrusor pressure. J Urol. 1995;154:1764–9.CrossRefGoogle Scholar
  4. 4.
    Girman CJ, Jacobsen SJ, Guess HA, Oesterling JE, Chute CG, Panser LA, et al. Natural history of prostatism: relationship among symptoms, prostate volume and peak urinary flow rate. J Urol. 1995;153:1510–5.CrossRefGoogle Scholar
  5. 5.
    Teng J, Zhang D, Li Y, Yin L, Wang K, Cui X, et al. Photoselective vaporization with the green light laser vs transurethral resection of the prostate for treating benign prostate hyperplasia: a systematic review and meta-analysis. BJU Int. 2013;111:312–23.CrossRefGoogle Scholar
  6. 6.
    Cornu JN, Ahyai S, Bachmann A, de la Rosette J, Gilling P, Gratzke C, et al. A systematic review and meta-analysis of functional outcomes and complications following transurethral procedures for lower urinary tract symptoms resulting from benign prostatic obstruction: an update. Eur Urol. 2015;67:1066–96.CrossRefGoogle Scholar
  7. 7.
    Nickel JC, Downey J, Young I, Boag S. Asymptomatic inflammation and/or infection in benign prostatic hyperplasia. BJU Int. 1999;84:976–81.CrossRefGoogle Scholar
  8. 8.
    Di Silverio F, Gentile V, De Matteis A, Mariotti G, Giuseppe V, Luigi PA, et al. Distribution of inflammation, pre-malignant lesions, incidental carcinoma in histologically confirmed benign prostatic hyperplasia: a retrospective analysis. Eur Urol. 2003;43:164–75.CrossRefGoogle Scholar
  9. 9.
    Barry MJ, Fowler FJ, O’Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. The American Urological Association symptom index for benign prostatic hyperplasia. The measurement Committee of the American Urological Association. J Urol. 1992;148:1549–57.CrossRefGoogle Scholar
  10. 10.
    Kohnen PW, Drach GW. Patterns of inflammation in prostatic hyperplasia: a histologic and bacteriologic study. J Urol. 1979;121:755–60.CrossRefGoogle Scholar
  11. 11.
    Delongchamps NB, de la Roza G, Chandan V, Jones R, Sunheimer R, Threatte G, et al. Evaluation of prostatitis in autopsied prostates–is chronic inflammation more associated with benign prostatic hyperplasia or cancer? J Urol. 2008;179:1736–40.CrossRefGoogle Scholar
  12. 12.••
    Inamura S, Ito H, Shinagawa T, Tsutsumiuchi M, Taga M, Kobayashi M, et al. Prostatic stromal inflammation is associated with bladder outlet obstruction in patients with benign prostatic hyperplasia. The Prostate. 2018;78:743–52 The authors retrospectively analyzed the prostate specimens of 179 men undergoing BPH surgery. Uniquely, they found that stromal inflammation was associated with a significant increase in prostate volume (63 mL vs 53 mL) and the existence of acute urinary retention (36.1% vs 11.4%). CrossRefGoogle Scholar
  13. 13.••
    Torkko KC, Wilson RS, Smith EE, Kusek JW, van Bokhoven A, Lucia MS. Prostate biopsy markers of inflammation are associated with risk of clinical progression of benign prostatic hyperplasia: findings from the MTOPS study. J Urol. 2015;194:454–61 980 men in the MTOPS study were part of a subset requiring baseline biopsy. Men diagnosed with cancer were excluded. Inflammatory markers (CD-4, CD-8, CD-45, CD-68) in the transition zone biopsy cores were analyzed and compared with their prospectively collected clinical variables. CD-4 was associated with BPH progression as defined by IPSS progression of 4 points (HR = 1.86 (1.16, 2.98)). CD-4, CD-8, and CD-68 was associated with an increased risk of developing acute urinary retention. CrossRefGoogle Scholar
  14. 14.
    Schenk JM, Kristal AR, Neuhouser ML, Tangen CM, White E, Lin DW, et al. Biomarkers of systemic inflammation and risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am J Epidemiol. 2010;171:571–82.CrossRefGoogle Scholar
  15. 15.
    Nickel JC, True LD, Krieger JN, Berger RE, Boag AH, Young ID. Consensus development of a histopathological classification system for chronic prostatic inflammation. BJU Int. 2001;87:797–805.CrossRefGoogle Scholar
  16. 16.
    McConnell JD, Roehrborn CG, Bautista OM, Andriole GL, Dixon CM, Kusek JW, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349:2387–98.CrossRefGoogle Scholar
  17. 17.
    Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362:1192–202.CrossRefGoogle Scholar
  18. 18.
    Nickel JC, Roehrborn CG, O’Leary MP, Bostwick DG, Somerville MC, Rittmaster RS. The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial. Eur Urol. 2008;54:1379–84.CrossRefGoogle Scholar
  19. 19.
    Roehrborn CG, Kaplan SA, Noble WD, Lucia MS, Slawin KM, McVary KT, et al. 1277: the impact of acute or chronic inflammation in baseline biopsy on the risk of clinical progression of BPH: results from the MTOPS study. J Urol. 2005;173:346.CrossRefGoogle Scholar
  20. 20.
    Barry MJ, Williford WO, Chang Y, Machi M, Jones KM, Walker-Corkery E, et al. Benign prostatic hyperplasia specific health status measures in clinical research: how much change in the American Urological Association symptom index and the benign prostatic hyperplasia impact index is perceptible to patients? J Urol. 1995;154:1770–4.CrossRefGoogle Scholar
  21. 21.
    Cantiello F, Cicione A, Salonia A, Autorino R, Ucciero G, Tucci L, et al. Metabolic syndrome correlates with peri-urethral fibrosis secondary to chronic prostate inflammation: evidence of a link in a cohort of patients undergoing radical prostatectomy. Int J Urol Off J Jpn Urol Assoc. 2014;21:264–9.Google Scholar
  22. 22.
    Cantiello F, Cicione A, Salonia A, Autorino R, Tucci L, Madeo I, et al. Periurethral fibrosis secondary to prostatic inflammation causing lower urinary tract symptoms: a prospective cohort study. Urology. 2013;81:1018–23.CrossRefGoogle Scholar
  23. 23.
    Ma J, Gharaee-Kermani M, Kunju L, Hollingsworth JM, Adler J, Arruda EM, et al. Prostatic fibrosis is associated with lower urinary tract symptoms. J Urol. 2012;188:1375–81.CrossRefGoogle Scholar
  24. 24.
    Chung JH, Yu JH, Sung LH, Noh CH, Chung JY. Effect of prostatitis on lower urinary tract symptoms: retrospective analysis of prostate biopsy tissue. Korean J Urol. 2012;53:109–13.CrossRefGoogle Scholar
  25. 25.
    Roehrborn CG. BPH progression: concept and key learning from MTOPS, ALTESS, COMBAT, and ALF-ONE. BJU Int. 2008;101(Suppl 3):17–21.CrossRefGoogle Scholar
  26. 26.
    Mishra VC, Allen DJ, Nicolaou C, Sharif H, Hudd C, Karim OM, et al. Does intraprostatic inflammation have a role in the pathogenesis and progression of benign prostatic hyperplasia? BJU Int. 2007;100:327–31.CrossRefGoogle Scholar
  27. 27.
    Nickel JC, Roehrborn CG, Castro-Santamaria R, Freedland SJ, Moreira DM. Chronic prostate inflammation is associated with severity and progression of benign prostatic hyperplasia, lower urinary tract symptoms and risk of acute urinary retention. J Urol. 2016;196:1493–8.CrossRefGoogle Scholar
  28. 28.
    Cakir SS, Polat EC, Ozcan L, Besiroglu H, Ötunctemur A, Ozbek E. The effect of prostatic inflammation on clinical outcomes in patients with benign prostate hyperplasia. Prostate Int. 2018;6:71–4.CrossRefGoogle Scholar
  29. 29.
    Hughes FM, Vivar NP, Kennis JG, Pratt-Thomas JD, Lowe DW, Shaner BE, et al. Inflammasomes are important mediators of cyclophosphamide-induced bladder inflammation. Am J Physiol Renal Physiol. 2014;306:F299–308.CrossRefGoogle Scholar
  30. 30.•
    Hughes FM, Hill HM, Wood CM, Edmondson AT, Dumas A, Foo W-C, et al. The NLRP3 inflammasome mediates inflammation produced by bladder outlet obstruction. J Urol. 2016;195:1598–605 This rat model elucidates the inflammatory mechanism by which bladder outlet obstruction leads to histologic changes in the bladder. Bladder outlet obstruction led to an increase in the NLRP3 inflammasome. This was associated with increased inflammation and bladder hypertrophy. Targeted inhibition of the inflammasome led to improvements in urodynamics and bladder hypertrophy. CrossRefGoogle Scholar
  31. 31.
    St Sauver JL, Jacobson DJ, McGree ME, Lieber MM, Jacobsen SJ. Protective association between nonsteroidal antiinflammatory drug use and measures of benign prostatic hyperplasia. Am J Epidemiol. 2006;164:760–8.CrossRefGoogle Scholar
  32. 32.
    Verhamme KM, Dieleman JP, Van Wijk MA, van der Lei J, Bosch JL, Stricker BH, et al. Nonsteroidal anti-inflammatory drugs and increased risk of acute urinary retention. Arch Intern Med. 2005;165:1547–51.CrossRefGoogle Scholar
  33. 33.
    Schenk JM, Calip GS, Tangen CM, Goodman P, Parsons JK, Thompson IM, et al. Indications for and use of nonsteroidal antiinflammatory drugs and the risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am J Epidemiol. 2012;176:156–63.CrossRefGoogle Scholar
  34. 34.
    Nygård LH, Talala K, Taari K, Tammela TLJ, Auvinen A, Murtola TJ. The effect of non-steroidal anti-inflammatory drugs on risk of benign prostatic hyperplasia. Prostate. 2017;77:1029–35.CrossRefGoogle Scholar
  35. 35.
    Sutcliffe S, Grubb Iii RL, Platz EA, Ragard LR, Riley TL, Kazin SS, et al. Non-steroidal anti-inflammatory drug use and the risk of benign prostatic hyperplasia-related outcomes and nocturia in the prostate, lung, colorectal, and ovarian cancer screening trial. BJU Int. 2012;110:1050–9.CrossRefGoogle Scholar
  36. 36.
    Di Silverio F, Bosman C, Salvatori M, Albanesi L, Proietti Pannunzi L, Ciccariello M, et al. Combination therapy with rofecoxib and finasteride in the treatment of men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Eur Urol. 2005;47:72–8.CrossRefGoogle Scholar
  37. 37.
    Ozdemir I, Bozkurt O, Demir O, Aslan G, Esen AA. Combination therapy with doxazosin and tenoxicam for the management of lower urinary tract symptoms. Urology. 2009;74:431–5.CrossRefGoogle Scholar
  38. 38.
    Kahokehr A, Vather R, Nixon A, Hill AG. Non-steroidal anti-inflammatory drugs for lower urinary tract symptoms in benign prostatic hyperplasia: systematic review and meta-analysis of randomized controlled trials. BJU Int. 2013;111:304–11.CrossRefGoogle Scholar
  39. 39.
    Liao CH, Chung SD, Kuo HC. Serum C-reactive protein levels are associated with residual urgency symptoms in patients with benign prostatic hyperplasia after medical treatment. Urology. 2011;78:1373–8.CrossRefGoogle Scholar
  40. 40.
    Rohrmann S, De Marzo AM, Smit E, Giovannucci E, Platz EA. Serum C-reactive protein concentration and lower urinary tract symptoms in older men in the third national health and nutrition examination survey (NHANES III). Prostate. 2005;62:27–33.CrossRefGoogle Scholar
  41. 41.
    St Sauver JL, Sarma AV, Jacobson DJ, McGree ME, Lieber MM, Girman CJ, et al. Associations between C-reactive protein and benign prostatic hyperplasia/lower urinary tract symptom outcomes in a population-based cohort. Am J Epidemiol. 2009;169:1281–90.CrossRefGoogle Scholar
  42. 42.
    Kupelian V, McVary KT, Barry MJ, Link CL, Rosen RC, Aiyer LP, et al. Association of C-reactive protein and lower urinary tract symptoms in men and women: results from Boston Area Community Health survey. Urology. 2009;73:950–7.CrossRefGoogle Scholar
  43. 43.
    Tarhan H, Ekin RG, Can E, Cakmak O, Yavascan O, Mutlubas Ozsan F, et al. C-reactive protein levels in girls with lower urinary tract symptoms. J Pediatr Urol. 2016;12(105):e1–4.Google Scholar
  44. 44.
    Peixoto CA,dos Gomes SFO. The role of phosphodiesterase-5 inhibitors in prostatic inflammation: a review. J Inflamm Lond Engl [Internet]. 2015 [cited 2019 Mar 10];12. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570643/
  45. 45.
    Zhang W, Zang N, Jiang Y, Chen P, Wang X, Zhang X. Upregulation of phosphodiesterase type 5 in the hyperplastic prostate. Sci Rep [Internet]. 2015 [cited 2019 Mar 10];5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674741/
  46. 46.
    Giuliano F, Ückert S, Maggi M, Birder L, Kissel J, Viktrup L. The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Eur Urol. 2013;63:506–16.CrossRefGoogle Scholar
  47. 47.
    Vignozzi L, Gacci M, Cellai I, Morelli A, Maneschi E, Comeglio P, et al. PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS. Prostate. 2013;73:1391–402.CrossRefGoogle Scholar
  48. 48.
    Morelli A, Comeglio P, Filippi S, Sarchielli E, Vignozzi L, Maneschi E, et al. Mechanism of action of phosphodiesterase type 5 inhibition in metabolic syndrome-associated prostate alterations: an experimental study in the rabbit. Prostate. 2013;73:428–41.CrossRefGoogle Scholar
  49. 49.
    Okamoto K, Kurita M, Yamaguchi H, Numakura Y, Oka M. Effect of tadalafil on chronic pelvic pain and prostatic inflammation in a rat model of experimental autoimmune prostatitis. Prostate. 2018;78:707–13.CrossRefGoogle Scholar
  50. 50.•
    Yamaguchi H, Kurita M, Okamoto K, Kotera T, Oka M. Voiding behavior and chronic pelvic pain in two types of rat nonbacterial prostatitis models: attenuation of chronic pelvic pain by repeated administration of tadalafil. The Prostate. 2019;79:446–53 Using rat non-bacterial prostatitis models, the authors demonstrated that chronic pelvic pain was increased after induction of the model. However, bladder function as measured by cystometric changes was not affected. Six-week administration of tadalafil attenuated the chronic pelvic pain. CrossRefGoogle Scholar
  51. 51.
    Gacci M, Corona G, Salvi M, Vignozzi L, McVary KT, Kaplan SA, et al. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol. 2012;61:994–1003.CrossRefGoogle Scholar
  52. 52.
    Zhang J, Li X, Yang B, Wu C, Fan Y, Li H. Alpha-blockers with or without phosphodiesterase type 5 inhibitor for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review and meta-analysis. World J Urol. 2019;37:143–53.CrossRefGoogle Scholar
  53. 53.
    Schmidt M, Naumann H, Weidler C, Schellenberg M, Anders S, Straub RH. Inflammation and sex hormone metabolism. Ann N Acad Sci. 2006;1069:236–46.CrossRefGoogle Scholar
  54. 54.
    Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Aging BLS of longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86:724–31.CrossRefGoogle Scholar
  55. 55.
    Vignozzi L, Cellai I, Santi R, Lombardelli L, Morelli A, Comeglio P, et al. Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells. J Endocrinol. 2012;214:31–43.CrossRefGoogle Scholar
  56. 56.
    Vignozzi L, Gacci M, Cellai I, Santi R, Corona G, Morelli A, et al. Fat boosts, while androgen receptor activation counteracts, BPH-associated prostate inflammation. Prostate. 2013;73:789–800.CrossRefGoogle Scholar
  57. 57.
    Traish A, Bolanos J, Nair S, Saad F, Morgentaler A. Do androgens modulate the pathophysiological pathways of inflammation? Appraising the contemporary evidence. J Clin Med. 2018;7.CrossRefGoogle Scholar
  58. 58.•
    Rył A, Rotter I, Grzywacz A, Małecka I, Skonieczna-Żydecka K, Grzesiak K, et al. Molecular analysis of the SRD5A1 and SRD5A2 genes in patients with benign prostatic hyperplasia with regard to metabolic parameters and selected hormone levels. Int J Environ Res Public Health. 2017;14 This study analyzed the relationships between the incidence of metabolic diseases and the genotypes of the 5훂-reductase enzyme polymorphisms in patients with BPH. 299 patients who presented for TURP had their blood drawn preoperatively. This found that certain polymorphisms of the SDR5A2 loci were associated with MetS. Google Scholar
  59. 59.
    Ge R, Wang Z, Bechis SK, Otsetov AG, Hua S, Wu S, et al. DNA methyl transferase 1 reduces expression of SRD5A2 in the aging adult prostate. Am J Pathol. 2015;185:870–82.CrossRefGoogle Scholar
  60. 60.
    Muller RL, Gerber L, Moreira DM, Andriole G, Hamilton RJ, Fleshner N, et al. Obesity is associated with increased prostate growth and attenuated prostate volume reduction by dutasteride. Eur Urol. 2013;63:1115–21.CrossRefGoogle Scholar
  61. 61.
    Mizoguchi S, Mori K, Wang Z, Liu T, Funahashi Y, Sato F, et al. Effects of estrogen receptor β stimulation in a rat model of non-bacterial prostatic inflammation. Prostate. 2017;77:803–11.CrossRefGoogle Scholar
  62. 62.
    Zhang B, Kwon OJ, Henry G, Malewska A, Wei X, Zhang L, et al. Non-cell-autonomous regulation of prostate epithelial homeostasis by androgen receptor. Mol Cell. 9(63):976–89.CrossRefGoogle Scholar
  63. 63.
    Ellem SJ, Wang H, Poutanen M, Risbridger GP. Increased endogenous estrogen synthesis leads to the sequential induction of prostatic inflammation (prostatitis) and prostatic pre-malignancy. Am J Pathol. 2009;175:1187–99.CrossRefGoogle Scholar
  64. 64.
    Kdadra M, Höckner S, Leung H, Kremer W, Schiffer E. Metabolomics biomarkers of prostate cancer: a systematic review. Diagn Basel Switz. 2019;9.CrossRefGoogle Scholar
  65. 65.
    Rubinow KB. An intracrine view of sex steroids, immunity, and metabolic regulation. Mol Metab. 2018;15:92–103.CrossRefGoogle Scholar
  66. 66.••
    Vignozzi L, Gacci M, Maggi M. Lower urinary tract symptoms, benign prostatic hyperplasia and metabolic syndrome. Nat Rev Urol. 2016;13:108–19 This review explores the pathogenic relationships between LUTS, metabolic syndrome and its components, inflammation, and sex steroid imbalance in men. They conclude that various metabolic insult lead to inflammation and alter the natural history of BPH and LUTS. More studies are needed to investigate lifestyle modifications to mitigate to progression of this disease process. CrossRefGoogle Scholar
  67. 67.
    Russo GI, Cimino S, Morgia G. Benign prostatic hyperplasia and metabolic syndrome: the expanding evidences of a new disease of aging male. Aging Male Off J Int Soc Study Aging Male. 2015;18:133–4.CrossRefGoogle Scholar
  68. 68.
    Vignozzi L, Morelli A, Sarchielli E, Comeglio P, Filippi S, Cellai I, et al. Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit. J Endocrinol. 2012;212:71–84.CrossRefGoogle Scholar
  69. 69.
    Gacci M, Corona G, Vignozzi L, Salvi M, Serni S, De Nunzio C, et al. Metabolic syndrome and benign prostatic enlargement: a systematic review and meta-analysis. BJU Int. 2015;115:24–31.CrossRefGoogle Scholar
  70. 70.
    Inouye BM, Hughes FM, Jin H, Lütolf R, Potnis KC, Routh JC, et al. Diabetic bladder dysfunction is associated with bladder inflammation triggered through hyperglycemia, not polyuria. Res Rep Urol. 2018;10:219–25.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Funahashi Y, Takahashi R, Mizoguchi S, Suzuki T, Takaoka E, Ni J, et al. Bladder overactivity and afferent hyperexcitability induced by prostate-to-bladder cross-sensitization in rats with prostatic inflammation. J Physiol. 2019;597:2063–78.CrossRefGoogle Scholar
  72. 72.
    Chen Y, Wu X, Liu J, Tang W, Zhao T, Zhang J. Distribution of convergent afferents innervating bladder and prostate at dorsal root Ganglia in rats. Urology. 2010;76:764–e1–6.PubMedGoogle Scholar

Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019

Authors and Affiliations

  • Granville L. Lloyd
    • 1
    Email author
  • Jeffrey M. Marks
    • 2
  • William A. Ricke
    • 3
  1. 1.Department of Surgery, Rocky Mountain Regional Veterans HospitalUniversity of Colorado Anschutz School of MedicineAuroraUSA
  2. 2.Division of UrologyUCSOMAuroraUSA
  3. 3.Department of Urology, Wisconsin Institutes for Medical ResearchUniversity of WisconsinMadisonUSA

Personalised recommendations