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Heat Shock Proteins and Pain

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Book cover Heat Shock Proteins in Human Diseases

Part of the book series: Heat Shock Proteins ((HESP,volume 21))

Abstract

Introduction

Pain, especially chronic pain, is a health issue affecting about one-third of the population all over the world. The sensitization of pain is highly associated with inflammatory responses to tissue damage and other harmful signals. The heat shock proteins (HSP) have been demonstrated to play central rolesin the inflammatory responses and pain via regulating the protein folding, maturation, activation, and degradation of proteins in varioussignal pathways. The objective of this chapter was to summarize the role of HSP in pain and pain drug-induced signal pathways and antinociception.

Methods

The authors reviewed papers of different HSP with an emphasis on pain and pain management.

Results

We highlight some basic concepts of pain and inflammatory responses, discuss the impact of inflammatory mediators, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α), on the sensitization of pain. We also summarize the role of HSP in different types of pain in animal models and human diseases and discuss the impact of HSP on pain drug-induced signalsand behavior.

Conclusions

HSP are highly involved in pain and pain treatment and could be targeted for improving therapeutic outcomes, even though the exact mechanisms remain unclear.

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Abbreviations

17-DMAG:

17-Dimethylaminoethylamino-17-demethoxygeldanamycin

Bdnf:

brain-derived neurotrophic factor

BiP:

binding immunoglobulin protein

CCI:

chronic constriction injury

CGRP:

calcitonin-gene-related peptide

cHsp60:

C. trachomatis Hsp60

CLR:

c-type lectin receptor

CNS:

central nervous system

COX:

cyclooxygenase enzymes

CP:

chronic bacterial prostatitis

CP/CPPS:

chronic bacterial prostatitis and chronic prostatitis​/chronic pelvic pain syndrome

DAMP:

danger-associated molecular pattern

DRG:

dorsal root ganglion

ELISA:

enzyme-linked immunosorbent assay

EP1:

Prostaglandin E2 receptor 1

ER:

endoplasmic reticulum

ERK:

extracellular signal-regulated kinase

GAPDH:

glyceraldehyde-3-phophate-dehyrogenase

Grp:

glucose-regulated protein

HDAC6:

histone deacetylase 6

Hsc:

heat shock cognate

Hsp:

heat shock protein

IL-1β:

interleukin (IL)-1 beta

IL-6:

interleukin 6

iNOS:

inducible nitric oxide synthase

JAK-STAT:

Janus kinase-signal transducer and activator of transcription

MAPK:

mitogen-activated protein kinase

MD-2:

myeloid differentiation factor 2

MEF2:

myocyte enhancer factor 2

MEK2:

mitogen-activated protein kinase kinase 2

MOR:

mu opioid receptor

NF-κB:

nuclear factor kappa-B

NLR:

NOD-like receptor

NOS:

nitric oxide synthase

PAMP:

pathogen-associated molecular pattern molecule

PCR:

polymerase chain reaction

PGE2:

prostaglandin E2

PID:

pelvic inflammatory disease

PKC:

protein kinase C

PNS:

peripheral nervous system

PRR:

pattern-recognition receptor

RLR:

retinoic acid-inducible gene-1-like receptor

ROS:

reactive oxygen species

sHsp:

small heat shock proteins

SOCS3:

suppressor of cytokine signaling 3

SOD:

superoxide dismutase

SP:

substance P

SRF:

serum-response factor

TLR:

toll-like receptor

TNF-α:

tumor necrosis factor alpha

TPA:

12-o-tetradecanoylphorbol 13- acetate

TRP:

transient receptor potential

TRPM3:

transient receptor potential melastatin-3

VR1:

Vanilloind receptor subtype 1

ZDF:

Zucker diabetic fatty

References

  1. Li C, Rui LL, Li Y-w, Zhu M, Liu Y, Pi Q, Meng F-y (2013a) Proteomic analysis of vincristine-induced neuropathic pain rat cerebral cortex disease. Guangdong Yixue 34:1981–1983

    CAS  Google Scholar 

  2. Li J, Richter K, Reinstein J, Buchner J (2013b) Integration of the accelerator Aha1 in the Hsp90 co-chaperone cycle. Nat Struct Mol Biol 20:326–331

    PubMed  Google Scholar 

  3. Zininga T, Ramatsui L, Shonhai A (2018) Heat shock proteins as immunomodulants. Molecules (Basel, Switz) 23:E2846

    Google Scholar 

  4. Martine P, Rebe C (2019) Heat shock proteins and inflammasomes. Int J Mol Sci 20:E4508

    PubMed  Google Scholar 

  5. Shende P, Bhandarkar S, Prabhakar B (2019) Heat shock proteins and their protective roles in stem cell biology. Stem Cell Rev Rep 15:637–651

    CAS  PubMed  Google Scholar 

  6. Klaips CL, Jayaraj GG, Hartl FU (2018) Pathways of cellular proteostasis in aging and disease. J Cell Biol 217:51–63

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Tsan MF, Gao B (2004) Heat shock protein and innate immunity. Cell Mol Immunol 1:274–279

    CAS  PubMed  Google Scholar 

  8. Amanvermez R, Acar E, Gunay M, Baydin A, Yardan T, Bek Y (2012) Hsp 70, hsCRP and oxidative stress in patients with acute coronary syndromes. Bosn J Basic Med Sci 12:102–107

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Dimas DT, Perlepe CD, Sergentanis TN, Misitzis I, Kontzoglou K, Patsouris E, Kouraklis G, Psaltopoulou T, Nonni A (2018) The prognostic significance of Hsp70/Hsp90 expression in breast cancer: a systematic review and meta-analysis. Anticancer Res 38:1551–1562

    CAS  PubMed  Google Scholar 

  10. Fan YX, Qian C, Liu B, Wang C, Liu H, Pan X, Teng P, Hu L, Zhang G, Han Y et al (2018) Induction of suppressor of cytokine signaling 3 via HSF-1-HSP70-TLR4 axis attenuates neuroinflammation and ameliorates postoperative pain. Brain Behav Immun 68:111–122

    CAS  PubMed  Google Scholar 

  11. Ranek MJ, Stachowski MJ, Kirk JA, Willis MS (2018) The role of heat shock proteins and co-chaperones in heart failure. Philos Trans R Soc Lond Ser B Biol Sci 373:20160530

    Google Scholar 

  12. Wu J, Liu T, Rios Z, Mei Q, Lin X, Cao S (2017) Heat shock proteins and cancer. Trends Pharmacol Sci 38:226–256

    CAS  PubMed  Google Scholar 

  13. Dukay B, Csoboz B, Toth ME (2019) Heat-shock proteins in neuroinflammation. Front Pharmacol 10:920

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Tsan MF, Gao B (2009) Heat shock proteins and immune system. J Leukoc Biol 85:905–910

    CAS  PubMed  Google Scholar 

  15. Basbaum AI, Bautista DM, Scherrer G, Julius D (2009) Cellular and molecular mechanisms of pain. Cell 139:267–284

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Pinho-Ribeiro FA, Verri WA Jr, Chiu IM (2017) Nociceptor sensory neuron-immune interactions in pain and inflammation. Trends Immunol 38:5–19

    CAS  PubMed  Google Scholar 

  17. Bujak JK, Kosmala D, Szopa IM, Majchrzak K, Bednarczyk P (2019) Inflammation, cancer and immunity-implication of TRPV1 channel. Front Oncol 9:1087

    PubMed  PubMed Central  Google Scholar 

  18. Tozaki-Saitoh H, Tsuda M (2019) Microglia-neuron interactions in the models of neuropathic pain. Biochem Pharmacol 169:113614

    CAS  PubMed  Google Scholar 

  19. Kunz S, Tegeder I, Coste O, Marian C, Pfenninger A, Corvey C, Karas M, Geisslinger G, Niederberger E (2005) Comparative proteomic analysis of the rat spinal cord in inflammatory and neuropathic pain models. Neurosci Lett 381:289–293

    CAS  PubMed  Google Scholar 

  20. Muley MM, Krustev E, McDougall JJ (2016) Preclinical assessment of inflammatory pain. CNS Neurosci Ther 22:88–101

    PubMed  Google Scholar 

  21. Gaskin DJ, Richard P (2012) The economic costs of pain in the United States. J Pain 13:715–724

    PubMed  Google Scholar 

  22. Jonsdottir T, Aspelund T, Jonsdottir H, Gunnarsdottir S (2014) The relationship between chronic pain pattern, interference with life and health-related quality of life in a nationwide community sample. Pain Manag Nurs 15:641–651

    PubMed  Google Scholar 

  23. Smith BH, Elliott AM, Chambers WA, Smith WC, Hannaford PC, Penny K (2001) The impact of chronic pain in the community. Fam Pract 18:292–299

    CAS  PubMed  Google Scholar 

  24. Williams AC, Craig KD (2016) Updating the definition of pain. Pain 157:2420–2423

    PubMed  Google Scholar 

  25. Cunha FQ, Poole S, Lorenzetti BB, Ferreira SH (1992) The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia. Br J Pharmacol 107:660–664

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Cunha TM, Verri WA Jr, Silva JS, Poole S, Cunha FQ, Ferreira SH (2005) A cascade of cytokines mediates mechanical inflammatory hypernociception in mice. Proc Natl Acad Sci U S A 102:1755–1760

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Ebbinghaus M, Uhlig B, Richter F, von Banchet GS, Gajda M, Brauer R, Schaible HG (2012) The role of interleukin-1beta in arthritic pain: main involvement in thermal, but not mechanical, hyperalgesia in rat antigen-induced arthritis. Arthritis Rheum 64:3897–3907

    CAS  PubMed  Google Scholar 

  28. Ferreira SH, Lorenzetti BB, Poole S (1993) Bradykinin initiates cytokine-mediated inflammatory hyperalgesia. Br J Pharmacol 110:1227–1231

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Malsch P, Andratsch M, Vogl C, Link AS, Alzheimer C, Brierley SM, Hughes PA, Kress M (2014) Deletion of interleukin-6 signal transducer gp130 in small sensory neurons attenuates mechanonociception and down-regulates TRPA1 expression. J Neurosci 34:9845–9856

    PubMed  PubMed Central  Google Scholar 

  30. Schoeniger-Skinner DK, Ledeboer A, Frank MG, Milligan ED, Poole S, Martin D, Maier SF, Watkins LR (2007) Interleukin-6 mediates low-threshold mechanical allodynia induced by intrathecal HIV-1 envelope glycoprotein gp120. Brain Behav Immun 21:660–667

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Souza GR, Cunha TM, Silva RL, Lotufo CM, Verri WA Jr, Funez MI, Villarreal CF, Talbot J, Sousa LP, Parada CA et al (2015) Involvement of nuclear factor kappa B in the maintenance of persistent inflammatory hypernociception. Pharmacol Biochem Behav 134:49–56

    CAS  PubMed  Google Scholar 

  32. Sun S, Diggins NH, Gunderson ZJ, Fehrenbacher JC, White FA, Kacena MA (2020) No pain, no gain? The effects of pain-promoting neuropeptides and neurotrophins on fracture healing. Bone 131:115109

    PubMed  Google Scholar 

  33. McEntire DM, Kirkpatrick DR, Dueck NP, Kerfeld MJ, Smith TA, Nelson TJ, Reisbig MD, Agrawal DK (2016) Pain transduction: a pharmacologic perspective. Expert Rev Clin Pharmacol 9:1069–1080

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Yam MF, Loh YC, Tan CS, Khadijah Adam S, Abdul Manan N, Basir R (2018) General pathways of pain sensation and the major neurotransmitters involved in pain regulation. Int J Mol Sci 19:2164

    PubMed Central  Google Scholar 

  35. Julius D, Basbaum AI (2001) Molecular mechanisms of nociception. Nature 413:203–210

    CAS  PubMed  Google Scholar 

  36. Eloqayli H (2018) Clinical decision-making in chronic spine pain: dilemma of image-based diagnosis of degenerative spine and generation mechanisms for nociceptive, radicular, and referred pain. Biomed Res Int 2018:8793843

    PubMed  PubMed Central  Google Scholar 

  37. Hildebrand C, Karlsson M, Risling M (1997) Ganglionic axons in motor roots and pia mater. Prog Neurobiol 51:89–128

    CAS  PubMed  Google Scholar 

  38. Meyer L, Taleb O, Patte-Mensah C, Mensah-Nyagan AG (2019) Neurosteroids and neuropathic pain management: basic evidence and therapeutic perspectives. Front Neuroendocrinol 55:100795

    CAS  PubMed  Google Scholar 

  39. Ronchetti S, Migliorati G, Delfino DV (2017) Association of inflammatory mediators with pain perception. Biomedicine & pharmacotherapy = Biomed Pharm 96:1445–1452

    CAS  Google Scholar 

  40. Kagan JC (2012) Signaling organelles of the innate immune system. Cell 151:1168–1178

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Rezaei N (2006) Therapeutic targeting of pattern-recognition receptors. Int Immunopharmacol 6:863–869

    CAS  PubMed  Google Scholar 

  42. O’Neill LA (2006) Targeting signal transduction as a strategy to treat inflammatory diseases. Nat Rev Drug Discov 5:549–563

    PubMed  Google Scholar 

  43. Ji RR, Chamessian A, Zhang YQ (2016) Pain regulation by non-neuronal cells and inflammation. Science (New York, NY) 354:572–577

    CAS  Google Scholar 

  44. Brusco I, Justino AB, Silva CR, Fischer S, Cunha TM, Scussel R, Machado-de-Avila RA, Ferreira J, Oliveira SM (2019) Kinins and their B1 and B2 receptors are involved in fibromyalgia-like pain symptoms in mice. Biochem Pharmacol 168:119–132

    CAS  PubMed  Google Scholar 

  45. Brusco I, Silva CR, Trevisan G, de Campos Velho Gewehr C, Rigo FK, La Rocca Tamiozzo L, Rossato MF, Tonello R, Dalmolin GD, de Almeida Cabrini D et al (2017) Potentiation of paclitaxel-induced pain syndrome in mice by angiotensin I converting enzyme inhibition and involvement of Kinins. Mol Neurobiol 54:7824–7837

    CAS  PubMed  Google Scholar 

  46. Calixto JB, Medeiros R, Fernandes ES, Ferreira J, Cabrini DA, Campos MM (2004) Kinin B1 receptors: key G-protein-coupled receptors and their role in inflammatory and painful processes. Br J Pharmacol 143:803–818

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Dray A, Perkins M (1993) Bradykinin and inflammatory pain. Trends Neurosci 16:99–104

    CAS  PubMed  Google Scholar 

  48. Ossipov MH, Dussor GO, Porreca F (2010) Central modulation of pain. J Clin Invest 120:3779–3787

    CAS  PubMed  PubMed Central  Google Scholar 

  49. McLean PG, Ahluwalia A, Perretti M (2000) Association between kinin B(1) receptor expression and leukocyte trafficking across mouse mesenteric postcapillary venules. J Exp Med 192:367–380

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Minville V, Mouledous L, Jaafar A, Couture R, Brouchet A, Frances B, Tack I, Girolami JP (2019) Tibial post fracture pain is reduced in kinin receptors deficient mice and blunted by kinin receptor antagonists. J Transl Med 17:346

    PubMed  PubMed Central  Google Scholar 

  51. Murakami M, Nakatani Y, Tanioka T, Kudo I (2002) Prostaglandin E synthase. Prostaglandins Other Lipid Mediat 68–69:383–399

    PubMed  Google Scholar 

  52. Markovic T, Jakopin Z, Dolenc MS, Mlinaric-Rascan I (2017) Structural features of subtype-selective EP receptor modulators. Drug Discov Today 22:57–71

    CAS  PubMed  Google Scholar 

  53. Afroz S, Arakaki R, Iwasa T, Oshima M, Hosoki M, Inoue M, Baba O, Okayama Y, Matsuka Y (2019) CGRP induces differential regulation of cytokines from satellite glial cells in trigeminal ganglia and orofacial nociception. Int J Mol Sci 20:711

    CAS  PubMed Central  Google Scholar 

  54. Al-Mazidi S, Alotaibi M, Nedjadi T, Chaudhary A, Alzoghaibi M, Djouhri L (2018) Blocking of cytokines signalling attenuates evoked and spontaneous neuropathic pain behaviours in the paclitaxel rat model of chemotherapy-induced neuropathy. Eur J Pain (Lond, Engl) 22:810–821

    CAS  Google Scholar 

  55. Cairns BE, Arendt-Nielsen L, Sacerdote P (2015) Perspectives in pain research 2014: neuroinflammation and glial cell activation: the cause of transition from acute to chronic pain? Scand J Pain 6:3–6

    PubMed  Google Scholar 

  56. Ortega E, Galvez I, Hinchado MD, Guerrero J, Martin-Cordero L, Torres-Piles S (2017) Anti-inflammatory effect as a mechanism of effectiveness underlying the clinical benefits of pelotherapy in osteoarthritis patients: regulation of the altered inflammatory and stress feedback response. Int J Biometeorol 61:1777–1785

    CAS  PubMed  Google Scholar 

  57. Rambe AS, Sjahrir H, Machfoed MH (2017) Tumour necrosis factor-alpha, Interleukin-1 and Interleukin-6 serum levels and its correlation with pain severity in chronic tension-type headache patients: analysing effect of dexketoprofen administration. Open Access Macedonian J Med Sci 5:54–57

    Google Scholar 

  58. Rhyu KW, Walsh AJ, O’Neill CW, Bradford DS, Lotz JC (2007) The short-term effects of electrosurgical ablation on proinflammatory mediator production by intervertebral disc cells in tissue culture. Spine J 7:451–458

    PubMed  Google Scholar 

  59. Kiguchi N, Maeda T, Kobayashi Y, Kondo T, Ozaki M, Kishioka S (2008) The critical role of invading peripheral macrophage-derived interleukin-6 in vincristine-induced mechanical allodynia in mice. Eur J Pharmacol 592:87–92

    CAS  PubMed  Google Scholar 

  60. Conaghan PG, Cook AD, Hamilton JA, Tak PP (2019) Therapeutic options for targeting inflammatory osteoarthritis pain. Nat Rev Rheumatol 15:355–363

    PubMed  Google Scholar 

  61. Hung AL, Lim M, Doshi TL (2017) Targeting cytokines for treatment of neuropathic pain. Scand J Pain 17:287–293

    PubMed  PubMed Central  Google Scholar 

  62. Siouti E, Andreakos E (2019) The many facets of macrophages in rheumatoid arthritis. Biochem Pharmacol 165:152–169

    CAS  PubMed  Google Scholar 

  63. Kregel KC (2002) Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J Appl Physiol (1985) 92:2177–2186

    CAS  Google Scholar 

  64. Spierings J, van Eden W (2017) Heat shock proteins and their immunomodulatory role in inflammatory arthritis. Rheumatology (Oxford) 56:198–208

    CAS  Google Scholar 

  65. De Maio A (1999) Heat shock proteins: facts, thoughts, and dreams. Shock 11:1–12

    PubMed  Google Scholar 

  66. Schlesinger MJ (1990) Heat shock proteins. J Biol Chem 265:12111–12114

    CAS  PubMed  Google Scholar 

  67. Stetler RA, Gan Y, Zhang W, Liou AK, Gao Y, Cao G, Chen J (2010) Heat shock proteins: cellular and molecular mechanisms in the central nervous system. Prog Neurobiol 92:184–211

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Jego G, Hazoume A, Seigneuric R, Garrido C (2013) Targeting heat shock proteins in cancer. Cancer Lett 332:275–285

    CAS  PubMed  Google Scholar 

  69. Alford KA, Glennie S, Turrell BR, Rawlinson L, Saklatvala J, Dean JL (2007) Heat shock protein 27 functions in inflammatory gene expression and transforming growth factor-beta-activated kinase-1 (TAK1)-mediated signaling. J Biol Chem 282:6232–6241

    CAS  PubMed  Google Scholar 

  70. Cai WF, Zhang XW, Yan HM, Ma YG, Wang XX, Yan J, Xin BM, Lv XX, Wang QQ, Wang ZY et al (2010) Intracellular or extracellular heat shock protein 70 differentially regulates cardiac remodelling in pressure overload mice. Cardiovasc Res 88:140–149

    CAS  PubMed  Google Scholar 

  71. He S, Yu Q, He Y, Hu R, Xia S, He J (2019) Dietary resveratrol supplementation inhibits heat stress-induced high-activated innate immunity and inflammatory response in spleen of yellow-feather broilers. Poult Sci 98(12):6378–6387

    CAS  PubMed  Google Scholar 

  72. Kang Y, Wang F, Lu Z, Ying H, Zhang H, Ding W, Wang C, Shi L (2013) MAPK kinase 3 potentiates chlamydia HSP60-induced inflammatory response through distinct activation of NF-kappaB. J Immunol 191:386–394

    CAS  PubMed  Google Scholar 

  73. Shrimali D, Shanmugam MK, Kumar AP, Zhang J, Tan BK, Ahn KS, Sethi G (2013) Targeted abrogation of diverse signal transduction cascades by emodin for the treatment of inflammatory disorders and cancer. Cancer Lett 341:139–149

    CAS  PubMed  Google Scholar 

  74. Yun TJ, Harning EK, Giza K, Rabah D, Li P, Arndt JW, Luchetti D, Biamonte MA, Shi J, Lundgren K et al (2011) EC144, a synthetic inhibitor of heat shock protein 90, blocks innate and adaptive immune responses in models of inflammation and autoimmunity. J Immunol 186:563–575

    CAS  PubMed  Google Scholar 

  75. Osterloh A, Breloer M (2008) Heat shock proteins: linking danger and pathogen recognition. Med Microbiol Immunol 197:1–8

    CAS  PubMed  Google Scholar 

  76. Padmini E, Usha Rani M (2011) Heat-shock protein 90 alpha (HSP90α) modulates signaling pathways towards tolerance of oxidative stress and enhanced survival of hepatocytes of Mugil cephalus. Cell Stress Chaperones 16:411–425

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Sulistyowati E, Lee MY, Wu LC, Hsu JH, Dai ZK, Wu BN, Lin MC, Yeh JL (2018) Exogenous heat shock cognate protein 70 suppresses LPS-induced inflammation by Down-regulating NF-kappaB through MAPK and MMP-2/-9 Pathways in macrophages. Molecules (Basel, Switz) 23:2124

    Google Scholar 

  78. Tian Y, Wang C, Chen S, Liu J, Fu Y, Luo Y (2019) Extracellular Hsp90alpha and clusterin synergistically promote breast cancer epithelial-to-mesenchymal transition and metastasis via LRP1. J Cell Sci 132:jcs228213

    CAS  PubMed  Google Scholar 

  79. GBD 2016 Mortality Collaborators (2017) Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-e2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet (Lond, Engl) 390:1084–1150

    Google Scholar 

  80. Taylor RP, Benjamin IJ (2005) Small heat shock proteins: a new classification scheme in mammals. J Mol Cell Cardiol 38:433–444

    CAS  PubMed  Google Scholar 

  81. Chowdary TK, Raman B, Ramakrishna T, Rao CM (2004) Mammalian Hsp22 is a heat-inducible small heat-shock protein with chaperone-like activity. Biochem J 381:379–387

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Bai F, Xi J, Higashikubo R, Andley UP (2004) Cell kinetic status of mouse lens epithelial cells lacking alphaA- and alphaB-crystallin. Mol Cell Biochem 265:115–122

    CAS  PubMed  Google Scholar 

  83. Charette SJ, Landry J (2000) The interaction of HSP27 with Daxx identifies a potential regulatory role of HSP27 in Fas-induced apoptosis. Ann N Y Acad Sci 926:126–131

    CAS  PubMed  Google Scholar 

  84. Haslbeck M, Franzmann T, Weinfurtner D, Buchner J (2005) Some like it hot: the structure and function of small heat-shock proteins. Nat Struct Mol Biol 12:842–846

    CAS  PubMed  Google Scholar 

  85. Ito H, Kamei K, Iwamoto I, Inaguma Y, Kato K (2001) Regulation of the levels of small heat-shock proteins during differentiation of C2C12 cells. Exp Cell Res 266:213–221

    CAS  PubMed  Google Scholar 

  86. Kamradt MC, Lu M, Werner ME, Kwan T, Chen F, Strohecker A, Oshita S, Wilkinson JC, Yu C, Oliver PG et al (2005) The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3. J Biol Chem 280:11059–11066

    CAS  PubMed  Google Scholar 

  87. Narberhaus F (2002) Alpha-crystallin-type heat shock proteins: socializing minichaperones in the context of a multichaperone network. Microbiol Mol Biol Rev 66:64–93; table of contents

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Van Montfort R, Slingsby C, Vierling E (2001) Structure and function of the small heat shock protein/alpha-crystallin family of molecular chaperones. Adv Protein Chem 59:105–156

    PubMed  Google Scholar 

  89. Ikwegbue PC, Masamba P, Oyinloye BE, Kappo AP (2017) Roles of heat shock proteins in apoptosis, oxidative stress, human inflammatory diseases, and cancer. Pharmaceuticals (Basel) 11:2

    Google Scholar 

  90. Ehrnsperger M, Hergersberg C, Wienhues U, Nichtl A, Buchner J (1998) Stabilization of proteins and peptides in diagnostic immunological assays by the molecular chaperone Hsp25. Anal Biochem 259:218–225

    CAS  PubMed  Google Scholar 

  91. Zwirowski S, Klosowska A, Obuchowski I, Nillegoda NB, Pirog A, Zietkiewicz S, Bukau B, Mogk A, Liberek K (2017) Hsp70 displaces small heat shock proteins from aggregates to initiate protein refolding. EMBO J 36:783–796

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Haslbeck M, Vierling E (2015) A first line of stress defense: small heat shock proteins and their function in protein homeostasis. J Mol Biol 427:1537–1548

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Mogk A, Bukau B, Kampinga HH (2018) Cellular handling of protein aggregates by disaggregation machines. Mol Cell 69:214–226

    CAS  PubMed  Google Scholar 

  94. Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR (2006) Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci 31:164–172

    CAS  PubMed  Google Scholar 

  95. Arrigo AP, Virot S, Chaufour S, Firdaus W, Kretz-Remy C, Diaz-Latoud C (2005) Hsp27 consolidates intracellular redox homeostasis by upholding glutathione in its reduced form and by decreasing iron intracellular levels. Antioxid Redox Signal 7:414–422

    CAS  PubMed  Google Scholar 

  96. Mehlen P, Hickey E, Weber LA, Arrigo AP (1997) Large unphosphorylated aggregates as the active form of hsp27 which controls intracellular reactive oxygen species and glutathione levels and generates a protection against TNFalpha in NIH-3T3-ras cells. Biochem Biophys Res Commun 241:187–192

    CAS  PubMed  Google Scholar 

  97. Shams S, Shafi S, Bodman-Smith K, Williams P, Mehta S, Ferns GA (2008) Anti-heat shock protein-27 (Hsp-27) antibody levels in patients with chest pain: association with established cardiovascular risk factors. Clinica Chim Acta Int J Clin Chem 395:42–46

    CAS  Google Scholar 

  98. Zhang ZW, Chunyan (2010) Clinical research of HSP27 in coronary heart disease. Jilin Yixue 31:6433–6434

    CAS  Google Scholar 

  99. Heidari-Bakavoli AR, Sahebkar A, Mobara N, Moohebati M, Tavallaie S, Rahsepar AA, Kazemi A, Alavi MS, Ghayour-Mobarhan M, Ferns GA (2012) Changes in plasma level of heat shock protein 27 after acute coronary syndrome. Angiology 63:12–16

    CAS  PubMed  Google Scholar 

  100. Plumier JC, Hopkins DA, Robertson HA, Currie RW (1997) Constitutive expression of the 27-kDa heat shock protein (Hsp27) in sensory and motor neurons of the rat nervous system. J Comp Neurol 384:409–428

    CAS  PubMed  Google Scholar 

  101. Costigan M, Mannion RJ, Kendall G, Lewis SE, Campagna JA, Coggeshall RE, Meridith-Middleton J, Tate S, Woolf CJ (1998) Heat shock protein 27: developmental regulation and expression after peripheral nerve injury. J Neurosci 18:5891–5900

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Hopkins DA, Plumier JC, Currie RW (1998) Induction of the 27-kDa heat shock protein (Hsp27) in the rat medulla oblongata after vagus nerve injury. Exp Neurol 153:173–183

    CAS  PubMed  Google Scholar 

  103. Wagstaff MJ, Collaco-Moraes Y, Smith J, de Belleroche JS, Coffin RS, Latchman DS (1999) Protection of neuronal cells from apoptosis by Hsp27 delivered with a herpes simplex virus-based vector. J Biol Chem 274:5061–5069

    CAS  PubMed  Google Scholar 

  104. Lewis SE, Mannion RJ, White FA, Coggeshall RE, Beggs S, Costigan M, Martin JL, Dillmann WH, Woolf CJ (1999) A role for HSP27 in sensory neuron survival. J Neurosci 19:8945–8953

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Brussee V, Guo G, Dong Y, Cheng C, Martinez JA, Smith D, Glazner GW, Fernyhough P, Zochodne DW (2008) Distal degenerative sensory neuropathy in a long-term type 2 diabetes rat model. Diabetes 57:1664–1673

    CAS  PubMed  Google Scholar 

  106. Korngut L, Ma CH, Martinez JA, Toth CC, Guo GF, Singh V, Woolf CJ, Zochodne DW (2012) Overexpression of human HSP27 protects sensory neurons from diabetes. Neurobiol Dis 47:436–443

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Parnas A, Nisemblat S, Weiss C, Levy-Rimler G, Pri-Or A, Zor T, Lund PA, Bross P, Azem A (2012) Identification of elements that dictate the specificity of mitochondrial Hsp60 for its co-chaperonin. PLoS One 7:e50318

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Czarnecka AM, Campanella C, Zummo G, Cappello F (2006) Mitochondrial chaperones in cancer: from molecular biology to clinical diagnostics. Cancer Biol Ther 5:714–720

    CAS  PubMed  Google Scholar 

  109. D’Souza SM, Brown IR (1998) Constitutive expression of heat shock proteins Hsp90, Hsc70, Hsp70 and Hsp60 in neural and non-neural tissues of the rat during postnatal development. Cell Stress Chaperones 3:188–199

    PubMed  PubMed Central  Google Scholar 

  110. Gammazza AM, Bucchieri F, Grimaldi LM, Benigno A, de Macario EC, Macario AJ, Zummo G, Cappello F (2012) The molecular anatomy of human Hsp60 and its similarity with that of bacterial orthologs and acetylcholine receptor reveal a potential pathogenetic role of anti-chaperonin immunity in myasthenia gravis. Cell Mol Neurobiol 32:943–947

    PubMed  Google Scholar 

  111. Marino Gammazza A, Colangeli R, Orban G, Pierucci M, Di Gennaro G, Lo Bello M, D’Aniello A, Bucchieri F, Pomara C, Valentino M et al (2015) Hsp60 response in experimental and human temporal lobe epilepsy. Sci Rep 5:9434

    PubMed  Google Scholar 

  112. Neumann E, Brandenburger T, Santana-Varela S, Deenen R, Kohrer K, Bauer I, Hermanns H, Wood JN, Zhao J, Werdehausen R (2016) MicroRNA-1-associated effects of neuron-specific brain-derived neurotrophic factor gene deletion in dorsal root ganglia. Mol Cell Neurosci 75:36–43

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Mor D, Bembrick AL, Austin PJ, Keay KA (2011) Evidence for cellular injury in the midbrain of rats following chronic constriction injury of the sciatic nerve. J Chem Neuroanat 41:158–169

    CAS  PubMed  Google Scholar 

  114. Zou W, Zhan X, Li M, Song Z, Liu C, Peng F, Guo Q (2012) Identification of differentially expressed proteins in the spinal cord of neuropathic pain models with PKCgamma silence by proteomic analysis. Brain Res 1440:34–46

    CAS  PubMed  Google Scholar 

  115. de Graeff-Meeder ER, van Eden W, Rijkers GT, Prakken BJ, Kuis W, Voorhorst-Ogink MM, van der Zee R, Schuurman HJ, Helders PJ, Zegers BJ (1995) Juvenile chronic arthritis: T cell reactivity to human HSP60 in patients with a favorable course of arthritis. J Clin Invest 95:934–940

    PubMed  PubMed Central  Google Scholar 

  116. Peeling RW, Kimani J, Plummer F, Maclean I, Cheang M, Bwayo J, Brunham RC (1997) Antibody to chlamydial hsp60 predicts an increased risk for chlamydial pelvic inflammatory disease. J Infect Dis 175:1153–1158

    CAS  PubMed  Google Scholar 

  117. Zhang X, He M, Cheng L, Chen Y, Zhou L, Zeng H, Pockley AG, Hu FB, Wu T (2008a) Elevated heat shock protein 60 levels are associated with higher risk of coronary heart disease in Chinese. Circulation 118:2687–2693

    CAS  PubMed  Google Scholar 

  118. Birnie DH, Vickers LE, Hillis WS, Norrie J, Cobbe SM (2005) Increased titres of anti-human heat shock protein 60 predict an adverse one year prognosis in patients with acute cardiac chest pain. Heart 91:1148–1153

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Mayer MP, Bukau B (2005) Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62:670–684

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Frydman J (2001) Folding of newly translated proteins in vivo: the role of molecular chaperones. Annu Rev Biochem 70:603–647

    CAS  PubMed  Google Scholar 

  121. Schaffitzel E, Rudiger S, Bukau B, Deuerling E (2001) Functional dissection of trigger factor and DnaK: interactions with nascent polypeptides and thermally denatured proteins. Biol Chem 382:1235–1243

    CAS  PubMed  Google Scholar 

  122. Pratt WB, Toft DO (2003) Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp Biol Med (Maywood) 228:111–133

    CAS  Google Scholar 

  123. Young JC, Barral JM, Ulrich Hartl F (2003) More than folding: localized functions of cytosolic chaperones. Trends Biochem Sci 28:541–547

    CAS  PubMed  Google Scholar 

  124. Chiang HL, Terlecky SR, Plant CP, Dice JF (1989) A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 246:382–385

    CAS  PubMed  Google Scholar 

  125. Meimaridou E, Gooljar SB, Chapple JP (2009) From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery. J Mol Endocrinol 42:1–9

    CAS  PubMed  Google Scholar 

  126. Daugaard M, Rohde M, Jaattela M (2007) The heat shock protein 70 family: highly homologous proteins with overlapping and distinct functions. FEBS Lett 581:3702–3710

    CAS  PubMed  Google Scholar 

  127. Evans CG, Chang L, Gestwicki JE (2010) Heat shock protein 70 (hsp70) as an emerging drug target. J Med Chem 53:4585–4602

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Zhang Y, Wang YH, Zhang XH, Ge HY, Arendt-Nielsen L, Shao JM, Yue SW (2008b) Proteomic analysis of differential proteins related to the neuropathic pain and neuroprotection in the dorsal root ganglion following its chronic compression in rats. Exp Brain Res 189:199–209

    CAS  PubMed  Google Scholar 

  129. Zhang YZ, Yan, Wang Y, Zhang X, Shao J, Yue S (2010) Proteomic analysis of differential proteins in dorsal root ganglion after chronic compression in rats. Zhongguo Kangfu Yixue Zazhi 25:928–936

    Google Scholar 

  130. Niinisto KE, Korolainen RV, Raekallio MR, Mykkanen AK, Koho NM, Ruohoniemi MO, Leppaluoto J, Poso AR (2010) Plasma levels of heat shock protein 72 (HSP72) and beta-endorphin as indicators of stress, pain and prognosis in horses with colic. Vet J (Lond, Engl: 1997) 184:100–104

    Google Scholar 

  131. Vizcaychipi MP, Xu L, Barreto GE, Ma D, Maze M, Giffard RG (2011) Heat shock protein 72 overexpression prevents early postoperative memory decline after orthopedic surgery under general anesthesia in mice. Anesthesiology 114:891–900

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Biebl MM, Buchner J (2019) Structure, function, and regulation of the Hsp90 machinery. Cold Spring Harb Perspect Biol 11:a034017

    CAS  PubMed  Google Scholar 

  133. Li J, Buchner J (2013) Structure, function and regulation of the hsp90 machinery. Biom J 36:106–117

    Google Scholar 

  134. Streicher JM (2019) The role of heat shock protein 90 in regulating pain, opioid signaling, and opioid antinociception. Vitam Horm 111:91–103

    PubMed  Google Scholar 

  135. Hutchinson MR, Ramos KM, Loram LC, Wieseler J, Sholar PW, Kearney JJ, Lewis MT, Crysdale NY, Zhang Y, Harrison JA et al (2009) Evidence for a role of heat shock protein-90 in toll like receptor 4 mediated pain enhancement in rats. Neuroscience 164:1821–1832

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Lewis SS, Hutchinson MR, Rezvani N, Loram LC, Zhang Y, Maier SF, Rice KC, Watkins LR (2010) Evidence that intrathecal morphine-3-glucuronide may cause pain enhancement via toll-like receptor 4/MD-2 and interleukin-1beta. Neuroscience 165:569–583

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Lee SH, Kim SY, Kim JH, Jung HY, Moon JH, Bae KH, Choi BT (2012) Phosphoproteomic analysis of electroacupuncture analgesia in an inflammatory pain rat model. Mol Med Rep 6:157–162

    CAS  PubMed  Google Scholar 

  138. Nascimento DSM, Potes CS, Soares ML, Ferreira AC, Malcangio M, Castro-Lopes JM, Neto FLM (2018) Drug-induced HSP90 inhibition alleviates pain in monoarthritic rats and alters the expression of new putative pain players at the DRG. Mol Neurobiol 55:3959–3975

    CAS  PubMed  Google Scholar 

  139. Boles RG, Hornung HA, Moody AE, Ortiz TB, Wong SA, Eggington JM, Stanley CM, Gao M, Zhou H, McLaughlin S et al (2015) Hurt, tired and queasy: specific variants in the ATPase domain of the TRAP1 mitochondrial chaperone are associated with common, chronic “functional” symptomatology including pain, fatigue and gastrointestinal dysmotility. Mitochondrion 23:64–70

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Kozawa O, Tanabe K, Matsuno H, Niwa M, Yamamoto T, Akamatsu S, Kato K, Dohi S, Uematsu T (2000) Pentobarbital, but not propofol, suppresses vasopressin-stimulated heat shock protein 27 induction in aortic smooth muscle cells. Anesthesiology 92:1807–1813

    CAS  PubMed  Google Scholar 

  141. Tanabe K, Akamatsu S, Suga H, Takai S, Kato K, Dohi S, Kozawa O (2005) Midazolam suppresses thrombin-induced heat shock protein 27 phosphorylation through inhibition of p38 mitogen-activated protein kinase in cardiac myocytes. J Cell Biochem 96:56–64

    CAS  PubMed  Google Scholar 

  142. Lin SH, Huang YN, Kao JH, Tien LT, Tsai RY, Wong CS (2016) Melatonin reverses morphine tolerance by inhibiting microglia activation and HSP27 expression. Life Sci 152:38–43

    CAS  PubMed  Google Scholar 

  143. Sharma HS, Ali SF, Patnaik R, Zimmermann-Meinzingen S, Sharma A, Muresanu DF (2011) Cerebrolysin attenuates heat shock protein (HSP 72 KD) expression in the rat spinal cord following morphine dependence and withdrawal: possible new therapy for pain management. Curr Neuropharmacol 9:223–235

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Ohara K, Shimizu K, Matsuura S, Ogiso B, Omagari D, Asano M, Tsuboi Y, Shinoda M, Iwata K (2013) Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation. J Neuroinflammation 10:139

    PubMed  PubMed Central  Google Scholar 

  145. Peng L, Liu M, Chang X, Yang Z, Yi S, Yan J, Peng Y (2014) Role of the nucleus tractus solitarii in the protection of pre-moxibustion on gastric mucosal lesions. Neural Regen Res 9:198–204

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Li YW, Zhao JM, Chen L, Shang HX, Wu LY, Bao CH, Dou CZ, Wu HG, Shi Y (2016) Effect of Electroacupuncture and Moxibustion on visceral pain and expression of VR 1 and HSP 70 of “Tianshu” (ST 25) region in colorectal distension-induced visceral hypersensitivity rats. Zhen ci yan jiu = Acupunct Res 41:291–297

    Google Scholar 

  147. Subadi I, Nugraha B, Laswati H, Josomuljono H (2017) Pain relief with wet cupping therapy in rats is mediated by heat shock protein 70 and ss-endorphin. Iran J Med Sci 42:384–391

    PubMed  PubMed Central  Google Scholar 

  148. Thakur V, Gonzalez M, Pennington K, Chattopadhyay M (2016) Viral vector mediated continuous expression of interleukin-10 in DRG alleviates pain in type 1 diabetic animals. Mol Cell Neurosci 72:46–53

    CAS  PubMed  Google Scholar 

  149. Malafoglia V, Traversetti L, Del Grosso F, Scalici M, Lauro F, Russo V, Persichini T, Salvemini D, Mollace V, Fini M et al (2016) Transient receptor potential Melastatin-3 (TRPM3) mediates nociceptive-like responses in Hydra vulgaris. PLoS One 11:e0151386

    PubMed  PubMed Central  Google Scholar 

  150. Guo H, Xu YM, Ye ZQ, Yu JH, Fu Q, Sa YL, Hu XY, Song LJ (2010) Heat-shock protein 70 expression in the seminal plasma of patients with chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome. Prostate Cancer Prostatic Dis 13:338–342

    CAS  PubMed  Google Scholar 

  151. Guo H, Xu YM, Ye ZQ, Yu JH (2012) Levels of cytokines and heat-shock protein 70 in the seminal plasma of patients with chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome. Zhonghua nan ke xue = Natl J Androl 18:1088–1092

    CAS  Google Scholar 

  152. Ustyol EA, Karaarslan F, Bekpinar S, Ozkuk K, Erdogan N (2017) Effects of Balneotherapy on serum levels of Shingosine-1-phosphate in patients with osteoarthritis. Altern Ther Health Med 23:10–14

    PubMed  Google Scholar 

  153. Chen YW, Li YT, Chen YC, Li ZY, Hung CH (2012) Exercise training attenuates neuropathic pain and cytokine expression after chronic constriction injury of rat sciatic nerve. Anesth Analg 114:1330–1337

    CAS  PubMed  Google Scholar 

  154. Chen YW, Hsieh PL, Chen YC, Hung CH, Cheng JT (2013) Physical exercise induces excess hsp72 expression and delays the development of hyperalgesia and allodynia in painful diabetic neuropathy rats. Anesth Analg 116:482–490

    CAS  PubMed  Google Scholar 

  155. Abul-Husn NS, Annangudi SP, Ma’ayan A, Ramos-Ortolaza DL, Stockton SD Jr, Gomes I, Sweedler JV, Devi LA (2011) Chronic morphine alters the presynaptic protein profile: identification of novel molecular targets using proteomics and network analysis. PLoS One 6:e25535

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Koshimizu TA, Tsuchiya H, Tsuda H, Fujiwara Y, Shibata K, Hirasawa A, Tsujimoto G, Fujimura A (2010) Inhibition of heat shock protein 90 attenuates adenylate cyclase sensitization after chronic morphine treatment. Biochem Biophys Res Commun 392:603–607

    CAS  PubMed  Google Scholar 

  157. Anyika M, McMullen M, Forsberg LK, Dobrowsky RT, Blagg BS (2016) Development of Noviomimetics as C-terminal Hsp90 inhibitors. ACS Med Chem Lett 7:67–71

    CAS  PubMed  Google Scholar 

  158. Urban MJ, Li C, Yu C, Lu Y, Krise JM, McIntosh MP, Rajewski RA, Blagg BS, Dobrowsky RT (2010) Inhibiting heat-shock protein 90 reverses sensory hypoalgesia in diabetic mice. ASN Neuro 2:e00040

    PubMed  PubMed Central  Google Scholar 

  159. Urban MJ, Pan P, Farmer KL, Zhao H, Blagg BS, Dobrowsky RT (2012) Modulating molecular chaperones improves sensory fiber recovery and mitochondrial function in diabetic peripheral neuropathy. Exp Neurol 235:388–396

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Tsai RY, Cheng YC, Wong CS (2015) (+)-Naloxone inhibits morphine-induced chemotaxis via prevention of heat shock protein 90 cleavage in microglia. J Formos Med Assoc 114:446–455

    CAS  PubMed  Google Scholar 

  161. Lei W, Mullen N, McCarthy S, Brann C, Richard P, Cormier J, Edwards K, Bilsky EJ, Streicher JM (2017) Heat-shock protein 90 (Hsp90) promotes opioid-induced anti-nociception by an ERK mitogen-activated protein kinase (MAPK) mechanism in mouse brain. J Biol Chem 292:10414–10428

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Lei W, Duron DI, Stine C, Mishra S, Blagg BSJ, Streicher JM (2019) The alpha isoform of heat shock protein 90 and the co-chaperones p23 and Cdc37 promote opioid anti-nociception in the brain. Front Mol Neurosci 12:294

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Grace PM, Strand KA, Galer EL, Rice KC, Maier SF, Watkins LR (2018) Protraction of neuropathic pain by morphine is mediated by spinal damage associated molecular patterns (DAMPs) in male rats. Brain Behav Immun 72:45–50

    CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to acknowledge institutional support from the Presbyterian College School of Pharmacy. We would also like to acknowledge our collaborator Dr. John Streicher from the University of Arizona and Dr. Brian Blagg from the University of Notre Dame for collaboration and valuable discussion on Hsp90 that contributed to the background of this work.

Disclosure of Interests

All authors declare they have no conflict of interest.

Ethical Approval for Studies Involving Humans

This article does not contain any studies with human participants performed by any of the authors.

Ethical Approval for Studies Involving Animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Approval was granted by the University of Arizona Institutional Animal Care and Use Committee (protocol # 16-078).

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  1. Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, Presbyterian College, Clinton, SC, USA

    Xin Chen, Amanda Smith, Christopher Plummer & Wei Lei

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Correspondence to Xin Chen or Wei Lei .

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  1. Department of Medicine and Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Medicine and Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Punit Kaur

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Chen, X., Smith, A., Plummer, C., Lei, W. (2020). Heat Shock Proteins and Pain. In: Asea, A.A.A., Kaur, P. (eds) Heat Shock Proteins in Human Diseases. Heat Shock Proteins, vol 21. Springer, Cham. https://doi.org/10.1007/7515_2020_20

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