Top

Published in:

Open Access 01-12-2006 | Research article

Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations

Authors: Gaurav Mukerji, Yiangos Yiangou, Stacey L Corcoran, Inger S Selmer, Graham D Smith, Christopher D Benham, Chas Bountra, Sanjiv K Agarwal, Praveen Anand

Published in: BMC Urology | Issue 1/2006

Abstract

Background

The recent identification of the cold-menthol sensory receptor (TRPM8; CMR1), provides us with an opportunity to advance our understanding of its role in the pathophysiology of bladder dysfunction, and its potential mediation of the bladder cooling reflex. In this study, we report the distribution of the cool and menthol receptor TRPM8 in the urinary bladder in patients with overactive and painful bladder syndromes, and its relationship with clinical symptoms.

Methods

Bladder specimens obtained from patients with painful bladder syndrome (PBS, n = 16), idiopathic detrusor overactivity (IDO, n = 14), and asymptomatic microscopic hematuria (controls, n = 17), were immunostained using specific antibodies to TRPM8; nerve fibre and urothelial immunostaining were analysed using fibre counts and computerized image analysis respectively. The results of immunohistochemistry were compared between the groups and correlated with the Pain, Frequency and Urgency scores.

Results

TRPM8-immunoreactive staining was observed in the urothelium and nerve fibres scattered in the suburothelium. The nerve fibre staining was seen in fine-calibre axons and thick (myelinated) fibres. There was marked increase of TRPM8-immunoreactive nerve fibres in IDO (P = 0.0249) and PBS (P < 0.0001) specimens, compared with controls. A significantly higher number of TRPM8-immunoreactive axons were also seen in the IDO (P = 0.0246) and PBS (P < 0.0001) groups. Urothelial TRPM8 and TRPM8-immunoreactive thick myelinated fibres appeared unchanged in IDO and PBS. The relative density of TRPM8-immunoreactive nerve fibres significantly correlated with the Frequency (r = 0.5487, P = 0.0004) and Pain (r = 0.6582, P < 0.0001) scores, but not Urgency score.

Conclusion

This study demonstrates increased TRPM8 in nerve fibres of overactive and painful bladders, and its relationship with clinical symptoms. TRPM8 may play a role in the symptomatology and pathophysiology of these disorders, and may provide an additional target for future overactive and painful bladder pharmacotherapy.

Available only for authorised users

Chai TC: Diagnosis of the painful bladder syndrome: current approaches to diagnosis. Clin Obstet Gynecol. 2002, 45: 250-258. 10.1097/00003081-200203000-00026.CrossRefPubMed

Abrams P: Describing bladder storage function: overactive bladder syndrome and detrusor overactivity. Urology. 2003, 62: 28-37; discussion 40-2. 10.1016/j.urology.2003.09.050.CrossRefPubMed

Tominaga M, Caterina MJ: Thermosensation and pain. J Neurobiol. 2004, 61: 3-12. 10.1002/neu.20079.CrossRefPubMed

Benham CD, Gunthorpe MJ, Davis JB: TRPV channels as temperature sensors. Cell Calcium. 2003, 33: 479-487. 10.1016/S0143-4160(03)00063-0.CrossRefPubMed

Clapham DE: TRP channels as cellular sensors. Nature. 2003, 426: 517-524. 10.1038/nature02196.CrossRefPubMed

Bors EH, Blinn KA: Spinal reflex activity from the vesical mucosa in paraplegic patients. AMA Arch Neurol Psychiatry. 1957, 78: 339-354.CrossRefPubMed

Fall M, Lindstrom S, Mazieres L: A bladder-to-bladder cooling reflex in the cat. J Physiol. 1990, 427: 281-300.CrossRefPubMedPubMedCentral

Lindstrom S, Mazieres L: Effect of menthol on the bladder cooling reflex in the cat. Acta Physiol Scand. 1991, 141: 1-10.CrossRefPubMed

Geirsson G: Evidence of cold receptors in the human bladder: effect of menthol on the bladder cooling reflex. J Urol. 1993, 150: 427-430.PubMed

10.

Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A: A TRP channel that senses cold stimuli and menthol. Cell. 2002, 108: 705-715. 10.1016/S0092-8674(02)00652-9.CrossRefPubMed

11.

McKemy DD, Neuhausser WM, Julius D: Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature. 2002, 416: 52-58. 10.1038/nature719.CrossRefPubMed

12.

Chuang HH, Neuhausser WM, Julius D: The super-cooling agent icilin reveals a mechanism of coincidence detection by a temperature-sensitive TRP channel. Neuron. 2004, 43: 859-869. 10.1016/j.neuron.2004.08.038.CrossRefPubMed

13.

Behrendt HJ, Germann T, Gillen C, Hatt H, Jostock R: Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay. Br J Pharmacol. 2004, 141: 737-745. 10.1038/sj.bjp.0705652.CrossRefPubMedPubMedCentral

14.

Tsavaler L, Shapero MH, Morkowski S, Laus R: Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res. 2001, 61: 3760-3769.PubMed

15.

Stein RJ, Santos S, Nagatomi J, Hayashi Y, Minnery BS, Xavier M, Patel AS, Nelson JB, Futrell WJ, Yoshimura N, Chancellor MB, De Miguel F: Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol. 2004, 172: 1175-1178. 10.1097/01.ju.0000134880.55119.cf.CrossRefPubMed

16.

Geirsson G, Lindstrom S, Fall M: The bladder cooling reflex and the use of cooling as stimulus to the lower urinary tract. J Urol. 1999, 162: 1890-1896. 10.1016/S0022-5347(05)68062-7.CrossRefPubMed

17.

Lindstrom S, Mazieres L, Jiang CH: Inhibition of the bladder cooling reflex in the awake state: an experimental study in the cat. J Urol. 2004, 172: 2051-2053. 10.1097/01.ju.0000134381.95274.a4.CrossRefPubMed

18.

Tsukimi Y, Mizuyachi K, Yamasaki T, Niki T, Hayashi F: Cold response of the bladder in guinea pig: involvement of transient receptor potential channel, TRPM8. Urology. 2005, 65: 406-410. 10.1016/j.urology.2004.10.006.CrossRefPubMed

19.

Payne CK, Terai A, Komatsu K: Research criteria versus clinical criteria for interstitial cystitis. Int J Urol. 2003, 10 Suppl: S7-S10. 10.1046/j.1442-2042.10.s1.3.x.CrossRefPubMed

20.

Parsons CL, Dell J, Stanford EJ, Bullen M, Kahn BS, Waxell T, Koziol JA: Increased prevalence of interstitial cystitis: previously unrecognized urologic and gynecologic cases identified using a new symptom questionnaire and intravesical potassium sensitivity. Urology. 2002, 60: 573-578. 10.1016/S0090-4295(02)01829-0.CrossRefPubMed

21.

Shu SY, Ju G, Fan LZ: The glucose oxidase-DAB-nickel method in peroxidase histochemistry of the nervous system. Neurosci Lett. 1988, 85: 169-171. 10.1016/0304-3940(88)90346-1.CrossRefPubMed

22.

Abe J, Hosokawa H, Okazawa M, Kandachi M, Sawada Y, Yamanaka K, Matsumura K, Kobayashi S: TRPM8 protein localization in trigeminal ganglion and taste papillae. Brain Res Mol Brain Res. 2005, 136: 91-98. 10.1016/j.molbrainres.2005.01.013.CrossRefPubMed

23.

Wasner G, Schattschneider J, Binder A, Baron R: Topical menthol--a human model for cold pain by activation and sensitization of C nociceptors. Brain. 2004, 127: 1159-1171. 10.1093/brain/awh134.CrossRefPubMed

24.

Habler HJ, Janig W, Koltzenburg M: Activation of unmyelinated afferent fibres by mechanical stimuli and inflammation of the urinary bladder in the cat. J Physiol. 1990, 425: 545-562.CrossRefPubMedPubMedCentral

25.

Yoshimura N, de Groat WC: Increased excitability of afferent neurons innervating rat urinary bladder after chronic bladder inflammation. J Neurosci. 1999, 19: 4644-4653.PubMed

26.

Mukerji G, Yiangou Y, Agarwal S, Anand P: Transient receptor potential vanilloid receptor TRPV1 in painful bladder syndrome and its correlation with pain. Journal of Urology. in press:

27.

Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, McIntyre P, Jegla T, Bevan S, Patapoutian A: ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003, 112: 819-829. 10.1016/S0092-8674(03)00158-2.CrossRefPubMed

28.

Lowe EM, Anand P, Terenghi G, Williams-Chestnut RE, Sinicropi DV, Osborne JL: Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis. Br J Urol. 1997, 79: 572-577.CrossRefPubMed

29.

Okragly AJ, Niles AL, Saban R, Schmidt D, Hoffman RL, Warner TF, Moon TD, Uehling DT, 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. 1999, 161: 438-41; discussion 441-2. 10.1016/S0022-5347(01)61915-3.CrossRefPubMed

30.

Babes A, Zorzon D, Reid G: Two populations of cold-sensitive neurons in rat dorsal root ganglia and their modulation by nerve growth factor. Eur J Neurosci. 2004, 20: 2276-2282. 10.1111/j.1460-9568.2004.03695.x.CrossRefPubMed

31.

Anand P: Capsaicin and menthol in the treatment of itch and pain: recently cloned receptors provide the key. Gut. 2003, 52: 1233-1235. 10.1136/gut.52.9.1233.CrossRefPubMedPubMedCentral

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2490/6/6/prepub

Title: Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations
Authors: Gaurav Mukerji
Yiangos Yiangou
Stacey L Corcoran
Inger S Selmer
Graham D Smith
Christopher D Benham
Chas Bountra
Sanjiv K Agarwal
Praveen Anand
Publication date: 01-12-2006
Publisher: BioMed Central
Published in: BMC Urology / Issue 1/2006
Electronic ISSN: 1471-2490
DOI: https://doi.org/10.1186/1471-2490-6-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2006

Langerhans cell histiocytosis on the penis: a case report

Ruptured renal artery aneurysm during pregnancy, a clinical dilemma

Frequency and patterns of early recanalization after vasectomy

Primary PEComa of the bladder treated with primary excision and adjuvant interferon-alpha immunotherapy: a case report

Adenocarcinoma of the caecum metastatic to the bladder: an unusual cause of haematuria

Intraprostatic injection of botulinum toxin type- A relieves bladder outlet obstruction in human and induces prostate apoptosis in dogs