アトピー性喘息マウスにおける顔面機械的過敏にTRPV1が寄与する

1. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular

mechanisms of pain. Cell. 2009;139(2):267e284. https://doi.org/10.1016/

j.cell.2009.09.028

2. Metze D. Neuroanatomy of the skin. In: Granstein RD, Luger TA, eds. Neuroimmunology of the Skin. 1st ed. Springer; 2009:3e12.

3. Berardesca E, Farage M, Maibach H. Sensitive skin: an overview. Int J Cosmet

Sci. 2013;35(1):2e8. https://doi.org/10.1111/j.1468-2494.2012.00754.x

€nder S, Szepietowski JC, et al. Definition of sensitive skin: an

4. Misery L, Sta

expert position paper from the special interest group on sensitive skin of the

international forum for the study of itch. Acta Derm Venereol. 2017;97(1):

4e6. https://doi.org/10.2340/00015555-2397

5. Farage MA. The prevalence of sensitive skin. Front Med (Lausanne). 2019;6:98.

https://doi.org/10.3389/fmed.2019.00098

6. Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med.

2006;355(21):2226e2235. https://doi.org/10.1056/NEJMra054308

re O, et al. Sensitive skin: an epidemiological

7. Willis CM, Shaw S, De Lacharrie

study. Br J Dermatol. 2001;145(2):258e263. https://doi.org/10.1046/j.13652133.2001.04343.x

8. Kira J, Yamasaki K, Kawano Y, Kobayashi T. Acute myelitis associated with

hyperIgEemia and atopic dermatitis. J Neurol Sci. 1997;148(2):199e203.

https://doi.org/10.1016/s0022-510x(97)05369-0

9. Isobe N, Kira J, Kawamura N, Ishizu T, Arimura K, Kawano Y. Neural damage

associated with atopic diathesis: a nationwide survey in Japan. Neurology.

2009;73(10):790e797. https://doi.org/10.1212/WNL.0b013e3181b6bb6b

10. Van Gerven L, Alpizar YA, Wouters MM, et al. Capsaicin treatment reduces

nasal hyperreactivity and transient receptor potential cation channel subfamily V, receptor 1 (TRPV1) overexpression in patients with idiopathic

rhinitis. J Allergy Clin Immunol. 2014;133(5):1332e1339.e3. https://doi.org/

10.1016/j.jaci.2013.08.026

11. Acosta CM, Luna C, Quirce S, Belmonte C, Gallar J. Changes in sensory activity

of ocular surface sensory nerves during allergic keratoconjunctivitis. Pain.

2013;154(11):2353e2362. https://doi.org/10.1016/j.pain.2013.07.012

12. Balestrini A, Joseph V, Dourado M, et al. A TRPA1 inhibitor suppresses

neurogenic inflammation and airway contraction for asthma treatment. J Exp

Med. 2021;218(4):e20201637. https://doi.org/10.1084/jem.20201637

13. Meng J, Li Y, Fischer MJM, Steinhoff M, Chen W, Wang J. Th2 modulation of

transient receptor potential channels: an unmet therapeutic intervention for

atopic dermatitis. Front Immunol. 2021;12, 696784. https://doi.org/10.3389/

fimmu.2021.696784

Acknowledgments

The authors thank Prof. M. Tominaga from the National Institute for Physiological Sciences for generously providing Trpv1/

mice and Trpv1/Trpa1/ mice. The authors thank Prof. Y.

Murata, Dr. M. Nishiyama, and Dr. Y. Honda for technical assistance. The authors thank Prof. M. Shinoda for his expert advice on

the von Frey test. The authors also thank Prof. T. Kiyoshima for

their experimental advice. The authors are grateful to the Division

of Biological Resources and Development, Analytical Research

Center for Experimental Sciences of Saga University, for animal

care and the Division of Instrumental Analysis, Analytical Research

Center for Experimental Sciences of Saga University, for technical

assistance. The authors thank J. Ludovic Croxford from Edanz

(https://jp.edanz.com/ac) for editing a draft of this manuscript.

This study is based on the doctoral thesis of A.C., submitted to the

14

Ailin Cao et al. / Lab Invest 103 (2023) 100149

38. Rehman R, Bhat YA, Panda L, Mabalirajan U. TRPV1 inhibition attenuates IL13 mediated asthma features in mice by reducing airway epithelial injury. Int

Immunopharmacol.

2013;15(3):597e605.

https://doi.org/10.1016/

j.intimp.2013.02.010

39. Cevikbas F, Wang X, Akiyama T, et al. A sensory neuron-expressed IL-31

receptor mediates T helper cell-dependent itch: involvement of TRPV1 and

TRPA1. J Allergy Clin Immunol. 2014;133(2):448e460. https://doi.org/

10.1016/j.jaci.2013.10.048

40. Meyer RA, Ringkamp M, Campbell JN, Raja SN. Peripheral mechanisms of

cutaneous nociception. In: McMahon SB, Koltzenburg M, eds. Wall and Melzack’s Textbook of Pain. 5th ed. Elsevier; 2006:3e34.

€umer W, Rossbach K.

41. Wilzopolski J, Kietzmann M, Mishra SK, Stark H, Ba

TRPV1 and TRPA1 channels are both involved downstream of histamineinduced itch. Biomolecules. 2021;11(8):1166. https://doi.org/10.3390/

biom11081166

42. von Buchholtz LJ, Ghitani N, Lam RM, Licholai JA, Chesler AT, Ryba NJP.

Decoding cellular mechanisms for mechanosensory discrimination. Neuron.

2021;109(2):285e298.e5. https://doi.org/10.1016/j.neuron.2020.10.028

43. Murthy SE, Loud MC, Daou I, et al. The mechanosensitive ion channel Piezo2

mediates sensitivity to mechanical pain in mice. Sci Transl Med.

2018;10(462), eaat9897. https://doi.org/10.1126/scitranslmed.aat9897

44. Szczot M, Liljencrantz J, Ghitani N, et al. PIEZO2 mediates injury-induced

tactile pain in mice and humans. Sci Transl Med. 2018;10(462), eaat9892.

https://doi.org/10.1126/scitranslmed.aat9892

45. Megat S, Ray PR, Tavares-Ferreira D, et al. Differences between dorsal root

and trigeminal ganglion nociceptors in mice revealed by translational

profiling. J Neurosci. 2019;39(35):6829e6847. https://doi.org/10.1523/

JNEUROSCI.2663-18.2019

46. Ji RR, Donnelly CR, Nedergaard M. Astrocytes in chronic pain and itch. Nat

Rev Neurosci. 2019;20(11):667e685. https://doi.org/10.1038/s41583-0190218-1

47. Stence N, Waite M, Dailey ME. Dynamics of microglial activation: a confocal

time-lapse analysis in hippocampal slices. Glia. 2001;33(3):256e266.

https://doi.org/10.1002/1098-1136(200103)33:3<256::AIDGLIA1024>3.0.CO;2-J

48. Schwerin SC, Chatterjee M, Imam-Fulani AO, et al. Progression of histopathological and behavioral abnormalities following mild traumatic brain

injury in the male ferret. J Neurosci Res. 2018;96(4):556e572. https://doi.org/

10.1002/jnr.24218

49. Kelkar M, Bohec P, Charras G. Mechanics of the cellular actin cortex: from

signalling to shape change. Curr Opin Cell Biol. 2020;66:69e78. https://

doi.org/10.1016/j.ceb.2020.05.008

50. Feldman-Goriachnik R, Hanani M. How do neurons in sensory ganglia

communicate with satellite glial cells? Brain Res. 2021;1760, 147384. https://

doi.org/10.1016/j.brainres.2021.147384

ndez R, Bastia

n Y, Ju

51. Rosas-Herna

arez Tello AJ, et al. AMPA receptors modulate the reorganization of F-actin in Bergmann glia cells through the activation of RhoA. J Neurochem. 2019;149(2):242e254. https://doi.org/10.1111/

jnc.14658

52. Lemes JBP, de Campos Lima T, Santos DO, et al. Participation of satellite glial

cells of the dorsal root ganglia in acute nociception. Neurosci Lett. 2018;676:

8e12. https://doi.org/10.1016/j.neulet.2018.04.003

53. Spray DC, Iglesias R, Shraer N, et al. Gap junction mediated signaling between

satellite glia and neurons in trigeminal ganglia. Glia. 2019;67(5):791e801.

https://doi.org/10.1002/glia.23554

54. Furuyashiki T, Arakawa Y, Takemoto-Kimura S, Bito H, Narumiya S. Multiple

spatiotemporal modes of actin reorganization by NMDA receptors and

voltage-gated Ca2þ channels. Proc Natl Acad Sci U S A. 2002;99(22):

14458e14463. https://doi.org/10.1073/pnas.212148999

55. Zhang Z, Kindrat AN, Sharif-Naeini R, Bourque CW. Actin filaments mediate

mechanical gating during osmosensory transduction in rat supraoptic nucleus neurons. J Neurosci. 2007;27(15):4008e4013. https://doi.org/10.1523/

JNEUROSCI.3278-06.2007

56. Omari SA, Adams MJ, Geraghty DP. TRPV1 channels in immune cells and

hematological malignancies. Adv Pharmacol. 2017;79:173e198. https://

doi.org/10.1016/bs.apha.2017.01.002

57. Choi JY, Lee HY, Hur J, et al. TRPV1 blocking alleviates airway inflammation

and remodeling in a chronic asthma murine model. Allergy Asthma Immunol

Res. 2018;10(3):216e224. https://doi.org/10.4168/aair.2018.10.3.216

58. Khalid S, Murdoch R, Newlands A, et al. Transient receptor potential vanilloid

1 (TRPV1) antagonism in patients with refractory chronic cough: a doubleblind randomized controlled trial. J Allergy Clin Immunol. 2014;134(1):

56e62. https://doi.org/10.1016/j.jaci.2014.01.038

59. Belvisi MG, Birrell MA, Wortley MA, et al. XEN-D0501, a novel transient receptor potential vanilloid 1 antagonist, does not reduce cough in refractory

cough patients. Am J Respir Crit Care Med. 2017;196(10):1255e1263. https://

doi.org/10.1164/rccm.201704-0769OC

60. Srour J, Bengel J, Linden T, et al. Efficacy of a skin care cream with TRPV1

inhibitor 4-t-butylcyclohexanol in the topical therapy of perioral dermatitis.

J Cosmet Dermatol. 2020;19(6):1409e1414. https://doi.org/10.1111/jocd.

13175

14. Nam JH, Kim WK. The role of TRP channels in allergic inflammation and its

clinical relevance. Curr Med Chem. 2020;27(9):1446e1468. https://doi.org/

10.2174/0929867326666181126113015

15. Bereiter DA, Hargreaves KM, Hu JW. Trigeminal mechanisms of nociception:

peripheral and brainstem organization. In: Masland RH, Albright TD,

Albright TD, et al., eds. The Senses: A Comprehensive Reference. Academic

Press; 2008:435e460. https://doi.org/10.1016/B978-012370880-9.00174-2

16. Urata K, Shinoda M, Honda K, et al. Involvement of TRPV1 and TRPA1 in

incisional intraoral and extraoral pain. J Dent Res. 2015;94(3):446e454.

https://doi.org/10.1177/0022034514565645

17. Honda K, Shinoda M, Furukawa A, Kita K, Noma N, Iwata K. TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats. Eur J Oral Sci.

2014;122(6):391e396. https://doi.org/10.1111/eos.12157

18. Caterina MJ, Leffler A, Malmberg AB, et al. Impaired nociception and pain

sensation in mice lacking the capsaicin receptor. Science. 2000;288(5464):

306e313. https://doi.org/10.1126/science.288.5464.306

19. Bautista DM, Sigal YM, Milstein AD, et al. Pungent agents from Szechuan

peppers excite sensory neurons by inhibiting two-pore potassium channels.

Nat Neurosci. 2008;11(7):772e779. https://doi.org/10.1038/nn.2143

20. Caceres AI, Brackmann M, Elia MD, et al. A sensory neuronal ion channel

essential for airway inflammation and hyperreactivity in asthma. Proc Natl

Acad Sci U S A. 2009;106(22):9099e9104. https://doi.org/10.1073/pnas.

0900591106

21. Kamp EH, Jones RCW, Tillman SR, Gebhart GF. Quantitative assessment and

characterization of visceral nociception and hyperalgesia in mice. Am J Physiol

Gastrointest Liver Physiol. 2003;284(3):G434eG444. https://doi.org/10.1152/

ajpgi.00324.2002

22. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994;53(1):

55e63. https://doi.org/10.1016/0165-0270(94)90144-9

€ Machelska H. Opioids and TRPV1 in the pe23. Labuz D, Spahn V, Celik MO,

ripheral control of neuropathic pain e defining a target site in the injured

nerve. Neuropharmacology. 2016;101:330e340. https://doi.org/10.1016/

j.neuropharm.2015.10.003

24. Yoshimoto RU, Aijima R, Ohyama Y, et al. Impaired junctions and invaded

macrophages in oral epithelia with oral pain. J Histochem Cytochem.

2019;67(4):245e256. https://doi.org/10.1369/0022155418812405

25. Takayama Y, Uta D, Furue H, Tominaga M. Pain-enhancing mechanism

through interaction between TRPV1 and anoctamin 1 in sensory neurons.

Proc Natl Acad Sci U S A. 2015;112(16):5213e5218. https://doi.org/10.1073/

pnas.1421507112

26. A practical guide of deconvolution application. Zeiss. Accessed March 22,

2023.

https://asset-downloads.zeiss.com/catalogs/download/mic/86baa

56d-3854-4eda-a342-693258d9c35a/EN_wp_LSM-Plus_Practical-Guide-ofDeconvolution.pdf

27. Zanier ER, Fumagalli S, Perego C, Pischiutta F, De Simoni MG. Shape descriptors of the “never resting” microglia in three different acute brain injury

models in mice. Intensive Care Med Exp. 2015;3:7. https://doi.org/10.1186/

s40635-015-0039-0

28. Aijima R, Wang B, Takao T, et al. The thermosensitive TRPV3 channel contributes to rapid wound healing in oral epithelia. FASEB J. 2015;29(1):

182e192. https://doi.org/10.1096/fj.14-251314

29. Yamasaki R, Fujii T, Wang B, et al. Allergic inflammation leads to neuropathic

pain via glial cell activation. J Neurosci. 2016;36(47):11929e11945. https://

doi.org/10.1523/JNEUROSCI.1981-16.2016

30. Ito D, Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y, Kohsaka S. Microglia-specific localisation of a novel calcium binding protein, Iba1. Mol Brain Res.

1998;57(1):1e9. https://doi.org/10.1016/s0169-328x(98)00040-0

31. Hanani M, Spray DC. Emerging importance of satellite glia in nervous system

function and dysfunction. Nat Rev Neurosci. 2020;21(9):485e498. https://

doi.org/10.1038/s41583-020-0333-z

32. Ji RR, Berta T, Nedergaard M. Glia and pain: is chronic pain a gliopathy? Pain.

2013;154(Suppl 1):S10eS28. https://doi.org/10.1016/j.pain.2013.06.022

33. Gouin O, L’Herondelle K, Lebonvallet N, et al. TRPV1 and TRPA1 in cutaneous

neurogenic and chronic inflammation: pro-inflammatory response induced

by their activation and their sensitization. Protein Cell. 2017;8(9):644e661.

https://doi.org/10.1007/s13238-017-0395-5

34. Tan LL, Bornstein JC, Anderson CR. Distinct chemical classes of medium-sized

transient receptor potential channel vanilloid 1-immunoreactive dorsal root

ganglion neurons innervate the adult mouse jejunum and colon. Neuroscience. 2008;156(2):334e343. https://doi.org/10.1016/j.neuroscience.2008.

06.071

35. De Logu F, Nassini R, Hegron A, et al. Schwann cell endosome CGRP signals

elicit periorbital mechanical allodynia in mice. Nat Commun. 2022;13(1):646.

https://doi.org/10.1038/s41467-022-28204-z

36. Millqvist E. TRPV1 and TRPM8 in treatment of chronic cough. Pharmaceuticals

(Basel). 2016;9(3):45. https://doi.org/10.3390/ph9030045

37. McGarvey LP, Butler CA, Stokesberry S, et al. Increased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in patients

with severe asthma. J Allergy Clin Immunol. 2014;133(3):704e712.e4. https://

doi.org/10.1016/j.jaci.2013.09.016

15

...