Abstract
This review focuses on TRPM8, one of the ~30 members of the diverse family of transient receptor potential (TRP) ion channels. Initially identified from the prostate, TRPM8 has been studied more extensively in the sensory system and is best established as a major transducer of environmental cold temperatures. An increasing body of evidence suggests that it may also be an important player in various chronic conditions, such as inflammatory/neuropathic pain and prostate cancer. Small molecule compounds that selectively modulate TRPM8 are beginning to emerge and will be critically valuable for better understanding the role of this channel in both physiological and pathological states, on which the prospects of TRPM8 as a viable therapeutic target rest.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Tsavaler L, Shapero MH, Morkowski S, Laus R (2001) 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 61:3760–3769
McKemy DD, Neuhausser WM, Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416:52–58
Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A (2002) A TRP channel that senses cold stimuli and menthol. Cell 108:705–715
Liu Y, Lubin ML, Reitz TL, Wang Y, Colburn RW, Flores CM, Qin N (2006) Molecular identification and functional characterization of a temperature-sensitive transient receptor potential channel (TRPM8) from canine. Eur J Pharmacol 530:23–32
Chuang HH, Neuhausser WM, Julius D (2004) The super-cooling agent icilin reveals a mechanism of coincidence detection by a temperature-sensitive TRP channel. Neuron 43:859–869
Myers BR, Sigal YM, Julius D (2009) Evolution of thermal response properties in a cold-activated TRP channel. PLoS One 4:e5741
Stewart AP, Egressy K, Lim A, Edwardson JM (2010) AFM imaging reveals the tetrameric structure of the TRPM8 channel. Biochem Biophys Res Commun 394:383–386
Dragoni I, Guida E, McIntyre P (2006) The cold and menthol receptor TRPM8 contains a functionally important double cysteine motif. J Biol Chem 281:37353–37360
Kuhn FJP, Knop G, Luckhoff A (2007) The transmembrane segment S6 determines cation versus anion selectivity of TRPM2 and TRPM8. J Biol Chem 282:27598–27609
Voets T, Owsianik G, Janssens A, Talavera K, Nilius B (2007) TRPM8 voltage sensor mutants reveal a mechanism for integrating thermal and chemical stimuli. Nat Chem Biol 3:174–182
Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B (2004) The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature 430:748–754
Phelps CB, Gaudet R (2007) The role of the N terminus and transmembrane domain of TRPM8 in channel localization and tetramerization. J Biol Chem 282:36474–36480
Erler I, Al-Ansary DM, Wissenbach U, Wagner TF, Flockerzi V, Niemeyer BA (2006) Trafficking and assembly of the cold-sensitive TRPM8 channel. J Biol Chem 281:38396–38404
Tsuruda PR, Julius D, Minor JDL (2006) Coiled coils direct assembly of a cold-activated TRP channel. Neuron 51:201–212
Jordt SE, Julius D (2002) Molecular basis for species-specific sensitivity to “hot” chili peppers. Cell 108:421–430
Gavva NR, Klionsky L, Qu Y, Shi L, Tamir R, Edenson S, Zhang TJ, Viswanadhan VN, Toth A, Pearce LV, Vanderah TW, Porreca F, Blumberg PM, Lile J, Sun Y, Wild K, Louis JC, Treanor JJ (2004) Molecular determinants of vanilloid sensitivity in TRPV1. J Biol Chem 279:20283–20295
Vriens J, Watanabe H, Janssens A, Droogmans G, Voets T, Nilius B (2004) Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4. Proc Natl Acad Sci USA 101:396–401
Bandell M, Dubin AE, Petrus MJ, Orth A, Mathur J, Hwang SW, Patapoutian A (2006) High-throughput random mutagenesis screen reveals TRPM8 residues specifically required for activation by menthol. Nat Neurosci 9:493–500
Rohacs T, Lopes CM, Michailidis I, Logothetis DE (2005) PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat Neurosci 8: 626–634
Brauchi S, Orta G, Salazar M, Rosenmann E, Latorre R (2006) A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels. J Neurosci 26:4835–4840
Henshall SM, Afar DE, Hiller J, Horvath LG, Quinn DI, Rasiah KK, Gish K, Willhite D, Kench JG, Gardiner-Garden M, Stricker PD, Scher HI, Grygiel JJ, Agus DB, Mack DH, Sutherland RL (2003) Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse. Cancer Res 63:4196–4203
Zhang L, Jones S, Brody K, Costa M, Brookes SJ (2004) Thermosensitive transient receptor potential channels in vagal afferent neurons of the mouse. Am J Physiol Gastrointest Liver Physiol 286:G983–G991
Zhao H, Sprunger LK, Simasko SM (2009) Expression of transient receptor potential channels and two-pore potassium channels in subtypes of vagal afferent neurons in rat. Am J Physiol Gastrointest Liver Physiol 298:G212–G221
Staaf S, Franck MCM, Marmigère F, Mattsson JP, Ernfors P (2010) Dynamic expression of the TRPM subgroup of ion channels in developing mouse sensory neurons. Gene Expr Patterns 10:65–74
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 (2004) Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol 172:1175–1178
De Blas GA, Darszon A, Ocampo AY, Serrano CJ, Castellano LE, Hernandez-Gonzalez EO, Chirinos M, Larrea F, Beltran C, Trevino CL (2009) TRPM8, a versatile channel in human sperm. PLoS One 4:e6095
Abe J, Hosokawa H, Okazawa M, Kandachi M, Sawada Y, Yamanaka K, Matsumura K, Kobayashi S (2005) TRPM8 protein localization in trigeminal ganglion and taste papillae. Brain Res Mol Brain Res 136:91–98
Mustafa S, Oriowo M (2005) Cooling-induced contraction of the rat gastric fundus: mediation via transient receptor potential (TRP) cation channel TRPM8 receptor and Rho-kinase activation. Clin Exp Pharmacol Physiol 32:832–838
Yang XR, Lin MJ, McIntosh LS, Sham JS (2006) Functional expression of transient receptor potential melastatin- and vanilloid-related channels in pulmonary arterial and aortic smooth muscle. Am J Physiol Lung Cell Mol Physiol 290:L1267–L1276
Sabnis AS, Shadid M, Yost GS, Reilly CA (2008) Human lung epithelial cells express a functional cold-sensing TRPM8 variant. Am J Respir Cell Mol Biol 39:466–474
Dhaka A, Earley TJ, Watson J, Patapoutian A (2008) Visualizing cold spots: TRPM8-expressing sensory neurons and their projections. J Neurosci 28:566–575
Du J, Yang X, Zhang L, Zeng YM (2009) Expression of TRPM8 in the distal cerebrospinal fluid-contacting neurons in the brain mesencephalon of rats. Cerebrospinal Fluid Res 6:3
Hondoh A, Ishida Y, Ugawa S, Ueda T, Shibata Y, Yamada T, Shikano M, Murakami S, Shimada S (2010) Distinct expression of cold receptors (TRPM8 and TRPA1) in the rat nodose-petrosal ganglion complex. Brain Res 1319:60–69
Sabnis AS, Reilly CA, Veranth JM, Yost GS (2008) Increased transcription of cytokine genes in human lung epithelial cells through activation of a TRPM8 variant by cold temperatures. Am J Physiol Lung Cell Mol Physiol 295:L194–L200
Hui K, Guo Y, Feng Z-P (2005) Biophysical properties of menthol-activated cold receptor TRPM8 channels. Biochem Biophys Res Commun 333:374–382
Brauchi S, Orio P, Latorre R (2004) Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8. Proc Natl Acad Sci USA 101:15494–15499
Malkia A, Madrid R, Meseguer V, de la Pena E, Valero M, Belmonte C, Viana F (2007) Bidirectional shifts of TRPM8 channel gating by temperature and chemical agents modulate the cold sensitivity of mammalian thermoreceptors. J Physiol 581:155–174
Kuhn FJ, Kuhn C, Luckhoff A (2009) Inhibition of TRPM8 by icilin distinct from desensitization induced by menthol and menthol derivatives. J Biol Chem 284:4102–4111
Behrendt HJ, Germann T, Gillen C, Hatt H, Jostock R (2004) 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 141:737–745
Bödding M, Wissenbach U, Flockerzi V (2007) Characterisation of TRPM8 as a pharmacophore receptor. Cell Calcium 42:618–628
Beck B, Bidaux G, Bavencoffe A, Lemonnier L, Thebault S, Shuba Y, Barrit G, Skryma R, Prevarskaya N (2007) Prospects for prostate cancer imaging and therapy using high-affinity TRPM8 activators. Cell Calcium 41:285–294
Hutchinson T, Liu Y, Flores CM, Qin N Differential agonist and antagonist effects of cannabinoids and other chemo-sensory stimuli on thermosensitive TRP channels. In Society for Neuroscience Meeting, Washington, DC, 2008
Vanden Abeele F, Zholos A, Bidaux G, Shuba Y, Thebault S, Beck B, Flourakis M, Panchin Y, Skryma R, Prevarskaya N (2006) Ca2+-independent phospholipase A2-dependent gating of TRPM8 by lysophospholipids. J Biol Chem 281:40174–40182
Andersson DA, Nash M, Bevan S (2007) Modulation of the cold-activated channel TRPM8 by lysophospholipids and polyunsaturated fatty acids. J Neurosci 27:3347–3355
Rohacs T, Nilius B (2007) Regulation of transient receptor potential (TRP) channels by phosphoinositides. Pflugers Arch 455:157–168
Liu B, Qin F (2005) Functional control of cold- and menthol-sensitive TRPM8 ion channels by phosphatidylinositol 4,5-bisphosphate. J Neurosci 25:1674–1681
Daniels RL, Takashima Y, McKemy DD (2009) Activity of the neuronal cold sensor TRPM8 is regulated by phospholipase C via the phospholipid phosphoinositol 4,5-bisphosphate. J Biol Chem 284:1570–1582
Premkumar LS, Raisinghani M, Pingle SC, Long C, Pimentel F (2005) Downregulation of transient receptor potential melastatin 8 by protein kinase C-mediated dephosphorylation. J Neurosci 25:11322–11329
Abe J, Hosokawa H, Sawada Y, Matsumura K, Kobayashi S (2006) Ca2+-dependent PKC activation mediates menthol-induced desensitization of transient receptor potential M8. Neurosci Lett 397:140–144
Bavencoffe A, Gkika D, Kondratskyi A, Beck B, Borowiec AS, Bidaux G, Busserolles J, Eschalier A, Shuba Y, Skryma R, Prevarskaya N (2010) The transient receptor potential channel TRPM8 is inhibited via the alpha 2A adrenoreceptor signaling pathway. J Biol Chem 285:9410–9419
Andersson DA, Chase HW, Bevan S (2004) TRPM8 activation by menthol, icilin, and cold is differentially modulated by intracellular pH. J Neurosci 24:5364–5369
Zakharian E, Thyagarajan B, French RJ, Pavlov E, Rohacs T (2009) Inorganic polyphosphate modulates TRPM8 channels. PLoS One 4:e5404
Morenilla-Palao C, Pertusa M, Meseguer V, Cabedo H, Viana F (2009) Lipid raft segregation modulates TRPM8 channel activity. J Biol Chem 284:9215–9224
Weil A, Moore SE, Waite NJ, Randall A, Gunthorpe MJ (2005) Conservation of functional and pharmacological properties in the distantly related temperature sensors TRPV1 and TRPM8. Mol Pharmacol 68:518–527
De Petrocellis L, Starowicz K, Moriello AS, Vivese M, Orlando P, Di Marzo V (2007) Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): effect of cAMP, cannabinoid CB1 receptors and endovanilloids. Exp Cell Res 313:1911–1920
Hu H-Z, Gu Q, Wang C, Colton CK, Tang J, Kinoshita-Kawada M, Lee L-Y, Wood JD, Zhu MX (2004) 2-Aminoethoxydiphenyl borate is a common activator of TRPV1, TRPV2, and TRPV3. J Biol Chem 279:35741–35748
Macpherson LJ, Hwang SW, Miyamoto T, Dubin AE, Patapoutian A, Story GM (2006) More than cool: promiscuous relationships of menthol and other sensory compounds. Mol Cell Neurosci 32:335–343
Niforatos W, Zhang XF, Lake MR, Walter KA, Neelands T, Holzman TF, Scott VE, Faltynek CR, Moreland RB, Chen J (2007) Activation of TRPA1 channels by the fatty acid amide hydrolase inhibitor 3'-carbamoylbiphenyl-3-yl cyclohexylcarbamate (URB597). Mol Pharmacol 71:1209–1216
Meseguer V, Karashima Y, Talavera K, D’Hoedt D, Donovan-Rodriguez T, Viana F, Nilius B, Voets T (2008) Transient receptor potential channels in sensory neurons are targets of the antimycotic agent clotrimazole. J Neurosci 28:576–586
Kraft R, Grimm C, Frenzel H, Harteneck C (2006) Inhibition of TRPM2 cation channels by N-(p-amylcinnamoyl)anthranilic acid. Br J Pharmacol 148:264–273
Benedikt J, Teisinger J, Vyklicky L, Vlachova V (2007) Ethanol inhibits cold-menthol receptor TRPM8 by modulating its interaction with membrane phosphatidylinositol 4,5-bisphosphate. J Neurochem 100:211–224
De Petrocellis L, Vellani V, Schiano-Moriello A, Marini P, Magherini PC, Orlando P, Di Marzo V (2008) Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J Pharmacol Exp Ther 325:1007–1015
Neeper MP, Liu Y, Hutchinson TL, Wang Y, Flores CM, Qin N (2007) Activation properties of heterologously expressed mammalian TRPV2: evidence for species dependence. J Biol Chem 282:15894–15902
Qin N, Neeper MP, Liu Y, Hutchinson TL, Lubin ML, Flores CM (2008) TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci 28:6231–6238
Jordt S-E, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID, Julius D (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427:260–265
Colburn RW, Matthews JM, Qin N, Liu Y, Hutchinson TL, Schneider CR, Stone DJJ, Lubin M, Pavlick KP, Kenigs VA, Dax SL, Brandt MR, Flores CM Small-molecule TRPM8 antagonist JNJ-39267631 reverses neuropathy-induced cold allodynia in rats. In 12th IASP World Congress on Pain, Glasgow, UK, 2008
Lashinger ES, Steiginga MS, Hieble JP, Leon LA, Gardner SD, Nagilla R, Davenport EA, Hoffman BE, Laping NJ, Su X (2008) AMTB, a TRPM8 channel blocker: evidence in rats for activity in overactive bladder and painful bladder syndrome. Am J Physiol Renal Physiol 295:F803–F810
Ortar G, De Petrocellis L, Morera L, Moriello AS, Orlando P, Morera E, Nalli M, Di Marzo V (2010) (–)-Menthylamine derivatives as potent and selective antagonists of transient receptor potential melastatin type-8 (TRPM8) channels. Bioorg Med Chem Lett 20:2729–2732
Foulkes T, Wood JN (2007) Mechanisms of cold pain. Channels (Austin) 1:154–160
Takashima Y, Daniels RL, Knowlton W, Teng J, Liman ER, McKemy DD (2007) Diversity in the neural circuitry of cold sensing revealed by genetic axonal labeling of transient receptor potential melastatin 8 neurons. J Neurosci 27:14147–14157
Kobayashi K, Fukuoka T, Obata K, Yamanaka H, Dai Y, Tokunaga A, Noguchi K (2005) Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with adelta/c-fibers and colocalization with trk receptors. J Comp Neurol 493:596–606
Nealen ML, Gold MS, Thut PD, Caterina MJ (2003) TRPM8 mRNA is expressed in a subset of cold-responsive trigeminal neurons from rat. J Neurophysiol 90:515–520
Reid G, Babes A, Pluteanu F (2002) A cold- and menthol-activated current in rat dorsal root ganglion neurones: properties and role in cold transduction. J Physiol 545:595–614
Okazawa M, Takao K, Hori A, Shiraki T, Matsumura K, Kobayashi S (2002) Ionic basis of cold receptors acting as thermostats. J Neurosci 22:3994–4001
Reid G, Flonta ML (2001) Physiology. Cold current in thermoreceptive neurons. Nature 413:480
McKemy DD (2007) TRPM8: The cold and menthol receptor. In: Liedtke WB, Heller S, (Eds.) TRP ion channel function in sensory transduction and cellular signaling cascades. CRC Press, London
Wei ET, Seid DA (1983) AG-3-5: a chemical producing sensations of cold. J Pharm Pharmacol 35:110–112
Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SE, Julius D (2007) The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448:204–208
Colburn RW, Lubin ML, Stone DJ Jr, Wang Y, Lawrence D, D’Andrea MR, Brandt MR, Liu Y, Flores CM, Qin N (2007) Attenuated cold sensitivity in TRPM8 null mice. Neuron 54:379–386
Dhaka A, Murray AN, Mathur J, Earley TJ, Petrus MJ, Patapoutian A (2007) TRPM8 is required for cold sensation in mice. Neuron 54:371–378
Munns C, AlQatari M, Koltzenburg M (2007) Many cold sensitive peripheral neurons of the mouse do not express TRPM8 or TRPA1. Cell Calcium 41:331–342
Babes A, Zorzon D, Reid G (2006) A novel type of cold-sensitive neuron in rat dorsal root ganglia with rapid adaptation to cooling stimuli. Eur J Neurosci 24:691–698
Madrid R, de la Pena E, Donovan-Rodriguez T, Belmonte C, Viana F (2009) Variable threshold of trigeminal cold-thermosensitive neurons is determined by a balance between TRPM8 and Kv1 potassium channels. J Neurosci 29:3120–3131
Attal N, Guirimand F, Brasseur L, Gaude V, Chauvin M, Bouhassira D (2002) Effects of IV morphine in central pain: a randomized placebo-controlled study. Neurology 58:554–563
Jorum E, Warncke T, Stubhaug A (2003) Cold allodynia and hyperalgesia in neuropathic pain: the effect of N-methyl-D-aspartate (NMDA) receptor antagonist ketamine – a double-blind, cross-over comparison with alfentanil and placebo. Pain 101:229–235
Hatem S, Attal N, Willer JC, Bouhassira D (2006) Psychophysical study of the effects of topical application of menthol in healthy volunteers. Pain 122:190–196
Namer B, Seifert F, Handwerker HO, Maihofner C (2005) TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol. NeuroReport 16:955–959
Wasner G, Schattschneider J, Binder A, Baron R (2004) Topical menthol – a human model for cold pain by activation and sensitization of C nociceptors. Brain 127:1159–1171
Engkvist O, Wahren LK, Wallin G, Torebjrk E, Nystrom B (1985) Effects of regional intravenous guanethidine block in posttraumatic cold intolerance in hand amputees. J Hand Surg Br 10:145–150
Campbell DA, Kay SP (1998) What is cold intolerance? J Hand Surg Br 23:3–5
Finnerup NB, Biering-Sorensen F, Johannesen IL, Terkelsen AJ, Juhl GI, Kristensen AD, Sindrup SH, Bach FW, Jensen TS (2005) Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled trial. Anesthesiology 102:1023–1030
Leung A, Wallace MS, Ridgeway B, Yaksh T (2001) Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain. Pain 91:177–187
Lindblom U, Verrillo RT (1979) Sensory functions in chronic neuralgia. J Neurol Neurosurg Psychiatry 42:422–435
Bini G, Cruccu G, Hagbarth KE, Schady W, Torebjork E (1984) Analgesic effect of vibration and cooling on pain induced by intraneural electrical stimulation. Pain 18:239–248
Sauls J (1999) Efficacy of cold for pain: fact or fallacy? Online J Knowl Synth Nurs 6:8
Hama AT (2002) Capsaicin-sensitive primary afferents mediate responses to cold in rats with a peripheral mononeuropathy. NeuroReport 13:461–464
Hao JX, Yu W, Xu XJ, Wiesenfeld-Hallin Z (1996) Capsaicin-sensitive afferents mediate chronic cold, but not mechanical, allodynia-like behavior in spinally injured rats. Brain Res 722:177–180
Kress M, Koltzenburg M, Reeh PW, Handwerker HO (1992) Responsiveness and functional attributes of electrically localized terminals of cutaneous C-fibers in vivo and in vitro. J Neurophysiol 68:581–595
LaMotte RH, Lundberg LE, Torebjork HE (1992) Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. J Physiol 448: 749–764
Okazawa M, Inoue W, Hori A, Hosokawa H, Matsumura K, Kobayashi S (2004) Noxious heat receptors present in cold-sensory cells in rats. Neurosci Lett 359:33–36
Viana F, de la Pena E, Belmonte C (2002) Specificity of cold thermotransduction is determined by differential ionic channel expression. Nat Neurosci 5:254–260
Hjerling-Leffler J, Alqatari M, Ernfors P, Koltzenburg M (2007) Emergence of functional sensory subtypes as defined by transient receptor potential channel expression. J Neurosci 27:2435–2443
Xing H, Ling J, Chen M, Gu JG (2006) Chemical and cold sensitivity of two distinct populations of TRPM8-expressing somatosensory neurons. J Neurophysiol 95:1221–1230
Green BG, Schoen KL (2007) Thermal and nociceptive sensations from menthol and their suppression by dynamic contact. Behav Brain Res 176:284–291
Frederick J, Buck ME, Matson DJ, Cortright DN (2007) Increased TRPA1, TRPM8, and TRPV2 expression in dorsal root ganglia by nerve injury. Biochem Biophys Res Commun 358:1058–1064
Xing H, Chen M, Ling J, Tan W, Gu JG (2007) TRPM8 mechanism of cold allodynia after chronic nerve injury. J Neurosci 27:13680–13690
Proudfoot CJ, Garry EM, Cottrell DF, Rosie R, Anderson H, Robertson DC, Fleetwood-Walker SM, Mitchell R (2006) Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain. Curr Biol 16:1591–1605
Gauchan P, Andoh T, Kato A, Kuraishi Y (2009) Involvement of increased expression of transient receptor potential melastatin 8 in oxaliplatin-induced cold allodynia in mice. Neurosci Lett 458:93–95
Caspani O, Zurborg S, Labuz D, Heppenstall PA (2009) The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain. PLoS One 4:e7383
Staaf S, Oerther S, Lucas G, Mattsson JP, Ernfors P (2009) Differential regulation of TRP channels in a rat model of neuropathic pain. Pain 144:187–199
Persson AK, Gebauer M, Jordan S, Metz-Weidmann C, Schulte AM, Schneider HC, Ding-Pfennigdorff D, Thun J, Xu XJ, Wiesenfeld-Hallin Z, Darvasi A, Fried K, Devor M (2009) Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain. Mol Pain 5:7
Obata K, Katsura H, Mizushima T, Yamanaka H, Kobayashi K, Dai Y, Fukuoka T, Tokunaga A, Tominaga M, Noguchi K (2005) TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury. J Clin Invest 115:2393–2401
Katsura H, Obata K, Mizushima T, Yamanaka H, Kobayashi K, Dai Y, Fukuoka T, Tokunaga A, Sakagami M, Noguchi K (2006) Antisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats. Exp Neurol 200:112–123
Mukerji G, Yiangou Y, Corcoran SL, Selmer IS, Smith GD, Benham CD, Bountra C, Agarwal SK, Anand P (2006) Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations. BMC Urol 6:6
Namer B, Kleggetveit IP, Handwerker H, Schmelz M, Jorum E (2008) Role of TRPM8 and TRPA1 for cold allodynia in patients with cold injury. Pain 139:63–72
Wright A (1870) Oil of peppermint as a local anaesthetic. Lancet 2464:726
Colvin LA, Johnson PR, Mitchell R, Fleetwood-Walker SM, Fallon M (2008) From bench to bedside: a case of rapid reversal of bortezomib-induced neuropathic pain by the TRPM8 activator, menthol. J Clin Oncol 26:4519–4520
Davies SJ, Harding LM, Baranowski AP (2002) A novel treatment of postherpetic neuralgia using peppermint oil. Clin J Pain 18:200–202
Wasner G, Naleschinski D, Binder A, Schattschneider J, McLachlan EM, Baron R (2008) The effect of menthol on cold allodynia in patients with neuropathic pain. Pain Med 9: 354–358
Klein AH, Sawyer CM, Carstens MI, Tsagareli M, Tsiklauri N, Carstens E (2010) Topical application of l-menthol induces heat analgesia, mechanical allodynia, and a biphasic effect on cold sensitivity in rats. Behav Brain Res 212:179–186
Galeotti N, Di Cesare Mannelli L, Mazzanti G, Bartolini A, Ghelardini C (2002) Menthol: a natural analgesic compound. Neurosci Lett 322:145–148
Calixto JB, Kassuya CA, Andre E, Ferreira J (2005) Contribution of natural products to the discovery of the transient receptor potential (TRP) channels family and their functions. Pharmacol Ther 106:179–208
Linte RM, Ciobanu C, Reid G, Babes A (2007) Desensitization of cold- and menthol-sensitive rat dorsal root ganglion neurones by inflammatory mediators. Exp Brain Res 178:89–98
Zhang L, Barritt GJ (2006) TRPM8 in prostate cancer cells: a potential diagnostic and prognostic marker with a secretory function? Endocr Relat Cancer 13:27–38
Bidaux G, Roudbaraki M, Merle C, Crepin A, Delcourt P, Slomianny C, Thebault S, Bonnal JL, Benahmed M, Cabon F, Mauroy B, Prevarskaya N (2005) Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement. Endocr Relat Cancer 12:367–382
Zhang L, Barritt GJ (2004) Evidence that TRPM8 is an androgen-dependent Ca2+ channel required for the survival of prostate cancer cells. Cancer Res 64:8365–8373
Fuessel S, Sickert D, Meye A, Klenk U, Schmidt U, Schmitz M, Rost AK, Weigle B, Kiessling A, Wirth MP (2003) Multiple tumor marker analyses (PSA, hK2, PSCA, trp-p8) in primary prostate cancers using quantitative RT-PCR. Int J Oncol 23:221–228
Prevarskaya N, Skryma R, Bidaux G, Flourakis M, Shuba Y (2007) Ion channels in death and differentiation of prostate cancer cells. Cell Death Differ 14:1295–1304
Bai VU, Murthy S, Chinnakannu K, Muhletaler F, Tejwani S, Barrack ER, Kim SH, Menon M, Veer Reddy GP (2010) Androgen regulated TRPM8 expression: a potential mRNA marker for metastatic prostate cancer detection in body fluids. Int J Oncol 36:443–450
Yang ZH, Wang XH, Wang HP, Hu LQ (2009) Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells. Asian J Androl 11:157–165
Yamamura H, Ugawa S, Ueda T, Morita A, Shimada S (2008) TRPM8 activation suppresses cellular viability in human melanoma. Am J Physiol Cell Physiol 295:C296–C301
Li Q, Wang X, Yang Z, Wang B, Li S (2009) Menthol induces cell death via the TRPM8 channel in the human bladder cancer cell line T24. Oncology 77:335–341
Thebault S, Lemonnier L, Bidaux G, Flourakis M, Bavencoffe A, Gordienko D, Roudbaraki M, Delcourt P, Panchin Y, Shuba Y, Skryma R, Prevarskaya N (2005) Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells. J Biol Chem 280:39423–39435
Tsuzuki K, Xing H, Ling J, Gu JG (2004) Menthol-induced Ca2+ release from presynaptic Ca2+ stores potentiates sensory synaptic transmission. J Neurosci 24:762–771
Lis A, Wissenbach U, Philipp SE (2005) Transcriptional regulation and processing increase the functional variability of TRPM channels. Naunyn Schmiedebergs Arch Pharmacol 371:315–324
Bidaux G, Flourakis M, Thebault S, Zholos A, Beck B, Gkika D, Roudbaraki M, Bonnal JL, Mauroy B, Shuba Y, Skryma R, Prevarskaya N (2007) Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function. J Clin Invest 117:1647–1657
Tajino K, Matsumura K, Kosada K, Shibakusa T, Inoue K, Fushiki T, Hosokawa H, Kobayashi S (2007) Application of menthol to the skin of whole trunk in mice induces autonomic and behavioral heat-gain responses. Am J Physiol Regul Integr Comp Physiol 293:R2128–R2135
Ruskin DN, Anand R, LaHoste GJ (2007) Menthol and nicotine oppositely modulate body temperature in the rat. Eur J Pharmacol 559:161–164
Ding Z, Gomez T, Werkheiser JL, Cowan A, Rawls SM (2008) Icilin induces a hyperthermia in rats that is dependent on nitric oxide production and NMDA receptor activation. Eur J Pharmacol 578:201–208
Gavva NR, Bannon AW, Surapaneni S, Hovland DN Jr, Lehto SG, Gore A, Juan T, Deng H, Han B, Klionsky L, Kuang R, Le A, Tamir R, Wang J, Youngblood B, Zhu D, Norman MH, Magal E, Treanor JJS, Louis J-C (2007) The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation. J Neurosci 27:3366–3374
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Liu, Y., Qin, N. (2011). TRPM8 in Health and Disease: Cold Sensing and Beyond. In: Islam, M. (eds) Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology, vol 704. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0265-3_10
Download citation
DOI: https://doi.org/10.1007/978-94-007-0265-3_10
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-0264-6
Online ISBN: 978-94-007-0265-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)