Peripheral nerve injury and sensitization underlie pain associated with oral cancer perineural invasion.
Journal
Pain
ISSN: 1872-6623
Titre abrégé: Pain
Pays: United States
ID NLM: 7508686
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
pubmed:
14
7
2020
medline:
26
3
2021
entrez:
14
7
2020
Statut:
ppublish
Résumé
Cancer invading into nerves, termed perineural invasion (PNI), is associated with pain. Here, we show that oral cancer patients with PNI report greater spontaneous pain and mechanical allodynia compared with patients without PNI, suggesting that unique mechanisms drive PNI-induced pain. We studied the impact of PNI on peripheral nerve physiology and anatomy using a murine sciatic nerve PNI model. Mice with PNI exhibited spontaneous nociception and mechanical allodynia. Perineural invasion induced afterdischarge in A high-threshold mechanoreceptors (HTMRs), mechanical sensitization (ie, decreased mechanical thresholds) in both A and C HTMRs, and mechanical desensitization in low-threshold mechanoreceptors. Perineural invasion resulted in nerve damage, including axon loss, myelin damage, and axon degeneration. Electrophysiological evidence of nerve injury included decreased conduction velocity, and increased percentage of both mechanically insensitive and electrically unexcitable neurons. We conclude that PNI-induced pain is driven by nerve injury and peripheral sensitization in HTMRs.
Identifiants
pubmed: 32658150
doi: 10.1097/j.pain.0000000000001986
pmc: PMC7572698
mid: NIHMS1608921
pii: 00006396-202011000-00016
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2592-2602Subventions
Organisme : NIDCR NIH HHS
ID : R01 DE029493
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016087
Pays : United States
Organisme : NIDCR NIH HHS
ID : R03 DE027777
Pays : United States
Organisme : NIDCR NIH HHS
ID : R21 DE026964
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE019796
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA163019
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA113833
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE026806
Pays : United States
Références
Amit M, Na'ara S, Gil Z. Mechanisms of cancer dissemination along nerves. Nat Rev Cancer 2016;16:399–408.
Armati PJ, Mathey EK. An update on Schwann cell biology—immunomodulation, neural regulation and other surprises. J Neurol Sci 2013;333:68–72.
Azam SH, Pecot CV. Cancer's got nerve: Schwann cells drive perineural invasion. J Clin Invest 2016;126:1242–4.
Bakst RL, Wong RJ. Mechanisms of perineural invasion. J Neurol Surg B Skull Base 2016;77:96–106.
Bapat AA, Hostetter G, Von Hoff DD, Han H. Perineural invasion and associated pain in pancreatic cancer. Nat Rev Cancer 2011;11:695–707.
Baron R, Hans G, Dickenson AH. Peripheral input and its importance for central sensitization. Ann Neurol 2013;74:630–6.
Bennett GJ. What is spontaneous pain and who has it? J Pain 2012;13:921–9.
Bhatheja K, Field J. Schwann cells: origins and role in axonal maintenance and regeneration. Int J Biochem Cell Biol 2006;38:1995–9.
Binmadi NO, Basile JR. Perineural invasion in oral squamous cell carcinoma: a discussion of significance and review of the literature. Oral Oncol 2011;47:1005–10.
Bjordal K, Ahlner-Elmqvist M, Hammerlid E, Boysen M, Evensen JF, Biorklund A, Jannert M, Westin T, Kaasa S. A prospective study of quality of life in head and neck cancer patients. Part II: longitudinal data. Laryngoscope 2001;111:1440–52.
Boada MD, Gutierrez S, Aschenbrenner CA, Houle TT, Hayashida K, Ririe DG, Eisenach JC. Nerve injury induces a new profile of tactile and mechanical nociceptor input from undamaged peripheral afferents. J Neurophysiol 2015;113:100–9.
Boada MD, Martin TJ, Parker R, Houle TT, Eisenach JC, Ririe DG. Recovery from nerve injury induced behavioral hypersensitivity in rats parallels resolution of abnormal primary sensory afferent signaling. PAIN 2020;161:949–59.
Boada MD, Martin TJ, Peters CM, Hayashida K, Harris MH, Houle TT, Boyden ES, Eisenach JC, Ririe DG. Fast-conducting mechanoreceptors contribute to withdrawal behavior in normal and nerve injured rats. PAIN 2014;155:2646–55.
Boada MD, Woodbury CJ. Physiological properties of mouse skin sensory neurons recorded intracellularly in vivo: temperature effects on somal membrane properties. J Neurophysiol 2007;98:668–80.
Boada MD, Woodbury CJ. Myelinated skin sensory neurons project extensively throughout adult mouse substantia gelatinosa. J Neurosci 2008;28:2006–14.
Cai Z, Finnie JW, Blumbergs PC, Manavis J, Ghabriel MN, Thompson PD. Early paranodal myelin swellings (tomacula) in an avian riboflavin deficiency model of demyelinating neuropathy. Exp Neurol 2006;198:65–71.
Cain DM, Wacnik PW, Turner M, Wendelschafer-Crabb G, Kennedy WR, Wilcox GL, Simone DA. Functional interactions between tumor and peripheral nerve: changes in excitability and morphology of primary afferent fibers in a murine model of cancer pain. J Neurosci 2001;21:9367–76.
Campana WM. Schwann cells: activated peripheral glia and their role in neuropathic pain. Brain Behav Immun 2007;21:522–7.
Campbell JN, Meyer RA. Mechanisms of neuropathic pain. Neuron 2006;52:77–92.
Chi AC, Katabi N, Chen HS, Cheng YL. Interobserver variation among pathologists in evaluating perineural invasion for oral squamous cell carcinoma. Head Neck Pathol 2016;10:451–64.
Chodroff L, Bendele M, Valenzuela V, Henry M, Ruparel S. EXPRESS: BDNF signaling contributes to oral cancer pain in a preclinical orthotopic rodent model. Mol Pain 2016;12:1744806916666841.
Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, Freeman R, Truini A, Attal N, Finnerup NB, Eccleston C, Kalso E, Bennett DL, Dworkin RH, Raja SN. Neuropathic pain. Nat Rev Dis Primers 2017;3:17002.
Connelly ST, Schmidt BL. Evaluation of pain in patients with oral squamous cell carcinoma. J Pain 2004;5:505–10.
Dalm BD, Reddy CG, Howard MA, Kang S, Brennan TJ. Conditioned place preference and spontaneous dorsal horn neuron activity in chronic constriction injury model in rats. PAIN 2015;156:2562–71.
Deborde S, Omelchenko T, Lyubchik A, Zhou Y, He S, McNamara WF, Chernichenko N, Lee S-Y, Barajas F, Chen C-H, Bakst RL, Vakiani E, He S, Hall A, Wong RJ. Schwann cells induce cancer cell dispersion and invasion. J Clin Invest 2016;126:1538–54.
Deborde S, Yu Y, Marcadis A, Chen CH, Fan N, Bakst RL, Wong RJ. An in vivo murine sciatic nerve model of perineural invasion. J Vis Exp 2018;134:56857.
Deuis JR, Dvorakova LS, Vetter I. Methods used to evaluate pain behaviors in rodents. Front Mol Neurosci 2017;10:284.
Djouhri L, Fang X, Koutsikou S, Lawson SN. Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and nonnociceptive DRG neurons: possible relationships to aspects of peripheral neuropathic pain and paresthesias. PAIN 2012;153:1824–36.
Djouhri L, Koutsikou S, Fang X, McMullan S, Lawson SN. Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors. J Neurosci 2006;26:1281–92.
Djouhri L, Lawson SN. Abeta-fiber nociceptive primary afferent neurons: a review of incidence and properties in relation to other afferent A-fiber neurons in mammals. Brain Res Brain Res Rev 2004;46:131–45.
Ein L, Mei C, Bracho O, Bas E, Monje P, Weed D, Sargi Z, Thomas G, Dinh C. Modulation of BDNF-TRKB interactions on Schwann cell-induced oral squamous cell carcinoma dispersion in vitro. Anticancer Res 2019;39:5933–42.
Fabrizi GM, Taioli F, Cavallaro T, Rigatelli F, Simonati A, Mariani G, Perrone P, Rizzuto N. Focally folded myelin in Charcot-Marie-Tooth neuropathy type 1B with Ser49Leu in the myelin protein zero. Acta Neuropathol 2000;100:299–304.
Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DL, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja SN, Rice AS, Serra J, Smith BH, Treede RD, Jensen TS. Neuropathic pain: an updated grading system for research and clinical practice. PAIN 2016;157:1599–606.
Grayson M, Furr A, Ruparel S. Depiction of oral tumor-induced trigeminal afferent responses using single-fiber electrophysiology. Scientific Rep 2019;9:4574.
Green BG, Schoen KL. Evidence that tactile stimulation inhibits nociceptive sensations produced by innocuous contact cooling. Behav Brain Res 2005;162:90–8.
Gutierrez S, Alvarado-Vazquez PA, Eisenach JC, Romero-Sandoval EA, Boada MD. Tachykinins modulate nociceptive responsiveness and sensitization: in vivo electrical characterization of primary sensory neurons in tachykinin knockout (Tac1 KO) mice. Mol Pain 2019;15:1744806919845750.
Hechler B, Carlson ER, Heidel RE, Fahmy MD, McCoy JM. Are oral pain and otalgia predictive of perineural invasion in squamous cell carcinoma of the oral tongue? J Oral Maxill Surg 2020. doi: 10.1016/j.joms.2020.03.029 [Epub ahead of print].
doi: 10.1016/j.joms.2020.03.029
Hua Y, Laserstein P, Helmstaedter M. Large-volume en-bloc staining for electron microscopy-based connectomics. Nat Commun 2015;6:7923.
Huyett P, Gilbert M, Liu L, Ferris RL, Kim S. A model for perineural invasion in head and neck squamous cell carcinoma. J Vis Exp 2017:55043.
Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol 2014;13:924–35.
Ji R-R, Chamessian A, Zhang YQ. Pain regulation by non-neuronal cells and inflammation. Science 2016;354:572–7.
Johnston M, Yu E, Kim J. Perineural invasion and spread in head and neck cancer. Expert Rev Anticancer Ther 2012;12:359–71.
Kakigi R, Shibasaki H. Mechanisms of pain relief by vibration and movement. J Neurol Neurosurg Psychiatry 1992;55:282–6.
King T, Vera-Portocarrero L, Gutierrez T, Vanderah TW, Dussor G, Lai J, Fields HL, Porreca F. Unmasking the tonic-aversive state in neuropathic pain. Nat Neurosci 2009;12:1364–6.
Kolokythas A, Connelly ST, Schmidt BL. Validation of the university of California san Francisco oral cancer pain questionnaire. J Pain 2007;8:950–3.
Lam DK, Dang D, Flynn AN, Hardt M, Schmidt BL. TMPRSS2, a novel membrane-anchored mediator in cancer pain. PAIN 2015;156:923–30.
Lam DK, Dang D, Zhang J, Dolan JC, Schmidt BL. Novel animal models of acute and chronic cancer pain: a pivotal role for PAR2. J Neurosci 2012;32:14178–83.
Li XY, Wang JH, Wu C. Knowing the neuronal mechanism of spontaneous pain to treat chronic pain in the future. Adv Exp Med Biol 2018;1099:115–24.
Ma CH, Omura T, Cobos EJ, Latremoliere A, Ghasemlou N, Brenner GJ, van Veen E, Barrett L, Sawada T, Gao F, Coppola G, Gertler F, Costigan M, Geschwind D, Woolf CJ. Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice. J Clin Invest 2011;121:4332–47.
Macfarlane TV, Wirth T, Ranasinghe S, Ah-See KW, Renny N, Hurman D. Head and neck cancer pain: systematic review of prevalence and associated factors. J Oral Maxillofac Res 2012;3:e1.
Mapplebeck JC, Beggs S, Salter MW. Sex differences in pain: a tale of two immune cells. PAIN 2016;157(suppl 1):S2–6.
McCoy ES, Taylor-Blake B, Street SE, Pribisko AL, Zheng J, Zylka MJ. Peptidergic CGRPalpha primary sensory neurons encode heat and itch and tonically suppress sensitivity to cold. Neuron 2013;78:138–51.
Menendez L, Lastra A, Fresno MF, Llames S, Meana A, Hidalgo A, Baamonde A. Initial thermal heat hypoalgesia and delayed hyperalgesia in a murine model of bone cancer pain. Brain Res 2003;969:102–9.
Millan MJ. The induction of pain: an integrative review. Prog Neurobiol 1999;57:1–164.
Minett MS, Quick K, Wood JN. Behavioral measures of pain thresholds. Curr Protoc Mouse Biol 2011;1:383–412.
Mogil JS. The etiology and symptomatology of spontaneous pain. J Pain 2012;13:932–3; discussion 934-935.
Ou M, Zhao W, Liu J, Liang P, Huang H, Yu H, Zhu T, Zhou C. The general anesthetic isoflurane bilaterally modulates neuronal excitability. iScience 2020;23:100760.
Quattrone A, Gambardella A, Bono F, Aguglia U, Bolino A, Bruni AC, Montesi MP, Oliveri RL, Sabatelli M, Tamburrini O, Valentino P, Van Broeckhoven C, Zappia M. Autosomal recessive hereditary motor and sensory neuropathy with focally folded myelin sheaths: clinical, electrophysiologic, and genetic aspects of a large family. Neurology 1996;46:1318–24.
Reyes-Gibby CC, Anderson KO, Merriman KW, Todd KH, Shete SS, Hanna EY. Survival patterns in squamous cell carcinoma of the head and neck: pain as an independent prognostic factor for survival. J Pain 2014;15:1015–22.
Roh J, Muelleman T, Tawfik O, Thomas SM. Perineural growth in head and neck squamous cell carcinoma: a review. Oral Oncol 2015;51:16–23.
Salvo E, Saraithong P, Curtin JG, Janal MN, Ye Y. Reciprocal interactions between cancer and Schwann cells contribute to oral cancer progression and pain. Heliyon 2019;5:e01223.
Scanlon CS, Banerjee R, Inglehart RC, Liu M, Russo N, Hariharan A, van Tubergen EA, Corson SL, Asangani IA, Mistretta CM, Chinnaiyan AM, D'Silva NJ. Galanin modulates the neural niche to favour perineural invasion in head and neck cancer. Nat Commun 2015;6:6885.
Scheff NN, Alemu RG, Klares R III, Wall IM, Yang SC, Dolan JC, Schmidt BL. Granulocyte-colony stimulating factor-induced neutrophil recruitment provides opioid-mediated endogenous anti-nociception in female mice with oral squamous cell carcinoma. Front Mol Neurosci 2019;12:217.
Scheff NN, Bhattacharya A, Dowse E, Dang RX, Dolan JC, Wang S, Kim H, Albertson DG, Schmidt BL. Neutrophil-mediated endogenous analgesia contributes to sex differences in oral cancer pain. Front Integr Neurosci 2018;12:52.
Scheff NN, Ye Y, Bhattacharya A, MacRae J, Hickman DN, Sharma AK, Dolan JC, Schmidt BL. Tumor necrosis factor alpha secreted from oral squamous cell carcinoma contributes to cancer pain and associated inflammation. PAIN 2017;158:2396–409.
Schmitd LB, Liu M, Scanlon CS, Banerjee R, D'Silva NJ. The chick chorioallantoic membrane in vivo model to assess perineural invasion in head and neck cancer. J Vis Exp 2019. doi: 10.3791/59296.
doi: 10.3791/59296
Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 2007;10:1361–8.
Shurin GV, Kruglov O, Ding F, Lin Y, Hao X, Keskinov AA, You Z, Lokshin AE, LaFramboise WA, Falo LD, Shurin MR, Bunimovich YL. Melanoma-induced reprogramming of Schwann cell signaling aids tumor growth. Cancer Res 2019;79:2736–47.
Smith BH, Raja SN. NeuPSIG: investing in solutions to the growing global challenge of neuropathic pain. Br J Anaesth 2017;119:705–8.
Sorge RE, Mapplebeck JC, Rosen S, Beggs S, Taves S, Alexander JK, Martin LJ, Austin JS, Sotocinal SG, Chen D, Yang M, Shi XQ, Huang H, Pillon NJ, Bilan PJ, Tu Y, Klip A, Ji RR, Zhang J, Salter MW, Mogil JS. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 2015;18:1081–3.
Sroka IC, Chopra H, Das L, Gard JM, Nagle RB, Cress AE. Schwann cells increase prostate and pancreatic tumor cell invasion using laminin binding A6 integrin. J Cell Biochem 2016;117:491–9.
Sun Y, Chen G, Zhou K, Zhu Y. A conditioned place preference protocol for measuring incubation of craving in rats. J Vis Exp 2018. doi: 10.3791/58384.
doi: 10.3791/58384
Tao F, Li Q, Liu S, Wu H, Skinner J, Hurtado A, Belegu V, Furmanski O, Yang Y, McDonald JW, Johns RA. Role of neuregulin-1/ErbB signaling in stem cell therapy for spinal cord injury-induced chronic neuropathic pain. Stem Cells 2013;31:83–91.
von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron 2012;73:638–52.
Walton J Lead asparate, an en bloc contrast stain particularly useful for ultrastructural enzymology. J Histochem Cytochem 1979;27:1337–42.
Wei Z, Fei Y, Su W, Chen G. Emerging role of Schwann cells in neuropathic pain: receptors, glial mediators and myelination. Front Cell Neurosci 2019;13:116.
Wilke SA, Antonios JK, Bushong EA, Badkoobehi A, Malek E, Hwang M, Terada M, Ellisman MH, Ghosh A. Deconstructing complexity: serial block-face electron microscopic analysis of the hippocampal mossy fiber synapse. J Neurosci 2013;33:507–22.
Wu G, Ringkamp M, Hartke TV, Murinson BB, Campbell JN, Griffin JW, Meyer RA. Early onset of spontaneous activity in uninjured C-fiber nociceptors after injury to neighboring nerve fibers. J Neurosci 2001;21:RC140.
Wu P, Arris D, Grayson M, Hung CN, Ruparel S. Characterization of sensory neuronal subtypes innervating mouse tongue. PLoS One 2018;13:e0207069.
Xiao WH, Bennett GJ. Persistent low-frequency spontaneous discharge in A-fiber and C-fiber primary afferent neurons during an inflammatory pain condition. Anesthesiology 2007;107:813–21.
Ydens E, Lornet G, Smits V, Goethals S, Timmerman V, Janssens S. The neuroinflammatory role of Schwann cells in disease. Neurobiol Dis 2013;55:95–103.
Ye Y, Bernabe DG, Salvo E, Viet CT, Ono K, Dolan JC, Janal M, Aouizerat BE, Miaskowski C, Schmidt BL. Alterations in opioid inhibition cause widespread nociception but do not affect anxiety-like behavior in oral cancer mice. Neuroscience 2017;363:50–61.
Ye Y, Dang D, Viet CT, Dolan JC, Schmidt BL. Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity. J Pain 2012;13:524–31.
Ye Y, Dang D, Zhang J, Viet CT, Lam DK, Dolan JC, Gibbs JL, Schmidt BL. Nerve growth factor links oral cancer progression, pain, and cachexia. Mol Cancer Ther 2011;10:1667–76.
Ye Y, Ono K, Bernabe DG, Viet CT, Pickering V, Dolan JC, Hardt M, Ford AP, Schmidt BL. Adenosine triphosphate drives head and neck cancer pain through P2X2/3 heterotrimers. Acta Neuropathol Commun 2014;2:62.
Ye Y, Scheff NN, Bernabe D, Salvo E, Ono K, Liu C, Veeramachaneni R, Viet CT, Viet DT, Dolan JC, Schmidt BL. Anti-cancer and analgesic effects of resolvin D2 in oral squamous cell carcinoma. Neuropharmacology 2018;139:182–93.
Ye Y, Woodbury CJ. Early postnatal loss of heat sensitivity among cutaneous myelinated nociceptors in Swiss-Webster mice. J Neurophysiol 2010;103:1385–96.
Yeh CF, Li WY, Chu PY, Kao SY, Chen YW, Lee TL, Hsu YB, Yang CC, Tai SK. Pretreatment pain predicts perineural invasion in oral squamous cell carcinoma: a prospective study. Oral Oncol 2016;61:115–19.
Zhang Z, Liu R, Jin R, Fan Y, Li T, Shuai Y, Li X, Wang X, Luo J. Integrating clinical and genetic analysis of perineural invasion in head and neck squamous cell carcinoma. Front Oncol 2019;9:434.