Skip to main content

Advertisement

SpringerLink
Log in

Emerging Targets for the Management of Osteoarthritis Pain

  • Bone and Joint Pain (J McDougall and S Bain, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Worldwide, osteoarthritis (OA) is one of the leading causes of chronic pain, for which adequate relief is not available. Ongoing peripheral input from the affected joint is a major factor in OA-associated pain. Therefore, this review focuses predominantly on peripheral targets emerging in the preclinical and clinical arena. Nerve growth factor is the most advanced of these targets, and its blockade has shown tremendous promise in clinical trials in knee OA. A number of different types of ion channels, including voltage-gated sodium channels and calcium channels, transient receptor potential channels, and acid-sensing ion channels, are important for neuronal excitability and play a role in pain genesis. Few channel blockers have been tested in preclinical models of OA, with varying results. Finally, we discuss some examples of G-protein coupled receptors, which may offer attractive therapeutic strategies for OA pain, including receptors for bradykinin, calcitonin gene-related peptide, and chemokines. Since many of the pathways described above can be selectively and potently targeted, they offer an exciting opportunity for pain management in OA, either systemically or locally.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance.•• Of major importance

  1. Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64(6):1697–707.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(9995):743–800.

    Article  PubMed Central  Google Scholar 

  3. Neogi T, Zhang Y. Epidemiology of osteoarthritis. Rheum Dis Clin North Am. 2013;39(1):1–19.

    Article  PubMed  Google Scholar 

  4. Neogi T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage. 2013;21(9):1145–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Malfait AM, Schnitzer T. Toward a mechanism-based approach of pain management in osteoarthritis. Nature Reviews Rheumatology. 2013;9:654–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Miller RE, Tran PB, Obeidat AM, Raghu P, Ishihara S, Miller RJ, et al. The Role of Peripheral Nociceptive Neurons in the Pathophysiology of Osteoarthritis Pain. Curr Osteoporos Rep. 2015;13(5):318–26.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Creamer P, Hunt M, Dieppe P. Pain mechanisms in osteoarthritis of the knee: effect of intraarticular anesthetic. J Rheumatol. 1996;23(6):1031–6.

    CAS  PubMed  Google Scholar 

  8. Schnitzer TJ, Marks JA. A systematic review of the efficacy and general safety of antibodies to NGF in the treatment of OA of the hip or knee. Osteoarthritis Cartilage. 2015;23 Suppl 1:S8–17.

    Article  PubMed  Google Scholar 

  9. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ren K, Dubner R. Interactions between the immune and nervous systems in pain. Nat Med. 2010;16(11):1267–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ji RR, Xu ZZ, Gao YJ. Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov. 2014;13(7):533–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lewin GR, Lechner SG, Smith ES. Nerve growth factor and nociception: from experimental embryology to new analgesic therapy. Handb Exp Pharmacol. 2014;220:251–82.

    Article  CAS  PubMed  Google Scholar 

  13. Stoppiello LA, Mapp PI, Wilson D, Hill R, Scammell BE, Walsh DA. Structural associations of symptomatic knee osteoarthritis. Arthritis Rheumatol. 2014;66(11):3018–27.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Iannone F, De Bari C, Dell’Accio F, Covelli M, Patella V, Lo Bianco G, et al. Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) in human osteoarthritic chondrocytes. Rheumatology (Oxford). 2002;41(12):1413–8.

    Article  CAS  Google Scholar 

  15. Pecchi E, Priam S, Gosset M, Pigenet A, Sudre L, Laiguillon MC, et al. Induction of nerve growth factor expression and release by mechanical and inflammatory stimuli in chondrocytes: possible involvement in osteoarthritis pain. Arthritis Res Ther. 2014;16(1):R16.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Blaney Davidson EN, van Caam AP, Vitters EL, Bennink MB, Thijssen E, van den Berg WB, et al. TGF-beta is a potent inducer of Nerve Growth Factor in articular cartilage via the ALK5-Smad2/3 pathway. Potential role in OA related pain? Osteoarthritis Cartilage. 2015;23(3):478–86.

    Article  CAS  PubMed  Google Scholar 

  17. Driscoll C, Chanalaris A, Knights C, Ismail H, Sacitharan PK, Gentry C, et al. Nociceptive Sensitizers Are Regulated in Damaged Joint Tissues, Including Articular Cartilage, When Osteoarthritic Mice Display Pain Behavior. Arthritis Rheumatol. 2016;68(4):857–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ashraf S, Mapp PI, Burston J, Bennett AJ, Chapman V, Walsh DA. Augmented pain behavioural responses to intra-articular injection of nerve growth factor in two animal models of osteoarthritis. Ann Rheum Dis. 2014;73(9):1710–8.

    Article  PubMed  Google Scholar 

  19. Ishikawa G, Koya Y, Tanaka H, Nagakura Y. Long-term analgesic effect of a single dose of anti-NGF antibody on pain during motion without notable suppression of joint edema and lesion in a rat model of osteoarthritis. Osteoarthritis Cartilage. 2015;23(6):925–32.

    Article  CAS  PubMed  Google Scholar 

  20. McNamee KE, Burleigh A, Gompels LL, Feldmann M, Allen SJ, Williams RO, et al. Treatment of murine osteoarthritis with TrkAd5 reveals a pivotal role for nerve growth factor in non-inflammatory joint pain. Pain. 2010;149(2):386–92.

    Article  CAS  PubMed  Google Scholar 

  21. Lascelles BD, Knazovicky D, Case B, Freire M, Innes JF, Drew AC, et al. A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain. BMC Vet Res. 2015;11:101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Eibl JK, Strasser BC, Ross GM. Structural, biological, and pharmacological strategies for the inhibition of nerve growth factor. Neurochem Int. 2012;61(8):1266–75.

    Article  CAS  PubMed  Google Scholar 

  23. Nwosu LN, Mapp PI, Chapman V, Walsh DA: Blocking the tropomyosin receptor kinase A (TrkA) receptor inhibits pain behaviour in two rat models of osteoarthritis. Ann Rheum Dis 2015. First evidence that TrkA inhibition blocks pain in experimental OA.

  24. Flannery C, Moran N, Blasioli D, Donahue K, Kane J, Gladysheva T, et al. A Novel, Locally Delivered TrkA Inhibitor for the Treatment of Joint Pain: Efficacy in Preclinical Models of Arthritis. ORS abstract. 2015.

  25. Catterall WA, Goldin AL, Waxman SG. International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev. 2005;57(4):397–409.

    Article  CAS  PubMed  Google Scholar 

  26. Liu M, Wood JN. The roles of sodium channels in nociception: implications for mechanisms of neuropathic pain. Pain Med. 2011;12 Suppl 3:S93–99.

    Article  PubMed  Google Scholar 

  27. Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature. 2006;444(7121):894–8.

    Article  CAS  PubMed  Google Scholar 

  28. Habib AM, Wood JN, Cox JJ. Sodium channels and pain. Handb Exp Pharmacol. 2015;227:39–56.

    Article  CAS  PubMed  Google Scholar 

  29. McDonnell A, Schulman B, Ali Z, Dib-Hajj SD, Brock F, Cobain S, et al. Inherited erythromelalgia due to mutations in SCN9A: natural history, clinical phenotype and somatosensory profile. Brain. 2016.

  30. Emery EC, Luiz AP, Wood JN: Na1.7 and other voltage-gated sodium channels as drug targets for pain relief. Expert Opin Ther Targets 2016.

  31. Reimann F, Cox JJ, Belfer I, Diatchenko L, Zaykin DV, McHale DP, et al. Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc Natl Acad Sci U S A. 2010;107(11):5148–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Valdes AM, Arden NK, Vaughn FL, Doherty SA, Leaverton PE, Zhang W, et al. Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain. Arthritis Care Res (Hoboken). 2011;63(3):440–4.

    CAS  Google Scholar 

  33. Schuelert N, McDougall JJ. Involvement of Nav 1.8 sodium ion channels in the transduction of mechanical pain in a rodent model of osteoarthritis. Arthritis Res Ther. 2012;14(1):R5. Important papers illustrating the role of sodium channels in OA pain.

  34. Rahman W, Dickenson AH. Osteoarthritis-dependent changes in antinociceptive action of Nav1.7 and Nav1.8 sodium channel blockers: an in vivo electrophysiological study in the rat. Neuroscience. 2015;295:103–16. Important papers illustrating the role of sodium channels in OA pain.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Rahman W, Dickenson AH. Antinociceptive effects of lacosamide on spinal neuronal and behavioural measures of pain in a rat model of osteoarthritis. Arthritis Res Ther. 2014;16(6):509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Malfait AM, Little CB, McDougall JJ. A commentary on modelling osteoarthritis pain in small animals. Osteoarthritis Cartilage. 2013;21(9):1316–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Duggan PJ, Tuck KL. Bioactive Mimetics of Conotoxins and other Venom Peptides. Toxins (Basel). 2015;7(10):4175–98.

    Article  CAS  Google Scholar 

  38. Just S, Heppelmann B. Voltage-gated calcium channels may be involved in the regulation of the mechanosensitivity of slowly conducting knee joint afferents in rat. Exp Brain Res. 2003;150(3):379–84.

    Article  CAS  PubMed  Google Scholar 

  39. Rahman W, Patel R, Dickenson AH. Electrophysiological evidence for voltage-gated calcium channel 2 (Cav2) modulation of mechano- and thermosensitive spinal neuronal responses in a rat model of osteoarthritis. Neuroscience. 2015;305:76–85. First in vivo evidence for an increased functional role of Cav2, likely Cav2.2, channels in mediating OA pain.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Vonsy JL, Ghandehari J, Dickenson AH. Differential analgesic effects of morphine and gabapentin on behavioural measures of pain and disability in a model of osteoarthritis pain in rats. Eur J Pain. 2009;13(8):786–93.

    Article  CAS  PubMed  Google Scholar 

  41. Bove SE, Laemont KD, Brooker RM, Osborn MN, Sanchez BM, Guzman RE, et al. Surgically induced osteoarthritis in the rat results in the development of both osteoarthritis-like joint pain and secondary hyperalgesia. Osteoarthritis Cartilage. 2006;14(10):1041–8.

    Article  CAS  PubMed  Google Scholar 

  42. Knights CB, Gentry C, Bevan S. Partial medial meniscectomy produces osteoarthritis pain-related behaviour in female C57BL/6 mice. Pain. 2012;153(2):281–92.

    Article  PubMed  Google Scholar 

  43. Julius D. TRP channels and pain. Annu Rev Cell Dev Biol. 2013;29:355–84.

    Article  CAS  PubMed  Google Scholar 

  44. Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature. 1999;398(6726):436–41.

    Article  CAS  PubMed  Google Scholar 

  45. Gavva NR, Treanor JJ, Garami A, Fang L, Surapaneni S, Akrami A, et al. Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain. 2008;136(1-2):202–10.

    Article  CAS  PubMed  Google Scholar 

  46. Wong GY, Gavva NR. Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: recent advances and setbacks. Brain Res Rev. 2009;60(1):267–77.

    Article  CAS  PubMed  Google Scholar 

  47. Valdes AM, De Wilde G, Doherty SA, Lories RJ, Vaughn FL, Laslett LL, et al. The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis. Ann Rheum Dis. 2011;70(9):1556–61.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kelly S, Chapman RJ, Woodhams S, Sagar DR, Turner J, Burston JJ, et al. Increased function of pronociceptive TRPV1 at the level of the joint in a rat model of osteoarthritis pain. Ann Rheum Dis. 2015;74(1):252–9.

    Article  CAS  PubMed  Google Scholar 

  49. Laslett LL, Jones G. Capsaicin for osteoarthritis pain. Prog Drug Res. 2014;68:277–91.

    CAS  PubMed  Google Scholar 

  50. Caires R, Luis E, Taberner FJ, Fernandez-Ballester G, Ferrer-Montiel A, Balazs EA, et al. Hyaluronan modulates TRPV1 channel opening, reducing peripheral nociceptor activity and pain. Nat Commun. 2015;6:8095. Study provides evidence that extracellular hyaluronan can reduce the excitability of the TRPV1 channel.

  51. Sluka KA, Gregory NS. The dichotomized role for acid sensing ion channels in musculoskeletal pain and inflammation. Neuropharmacology. 2015;94:58–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bohlen CJ, Chesler AT, Sharif-Naeini R, Medzihradszky KF, Zhou S, King D, et al. A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain. Nature. 2011;479(7373):410–4. Two very interesting papers using toxins to highlight the role of ASIC channels in pain.

  53. Diochot S, Baron A, Salinas M, Douguet D, Scarzello S, Dabert-Gay AS, et al. Black mamba venom peptides target acid-sensing ion channels to abolish pain. Nature. 2012;490(7421):552–5. Two very interesting papers using toxins to highlight the role of ASIC channels in pain.

    Article  CAS  PubMed  Google Scholar 

  54. Sugimura N, Ikeuchi M, Izumi M, Kawano T, Aso K, Kato T, et al. Repeated intra-articular injections of acidic saline produce long-lasting joint pain and widespread hyperalgesia. Eur J Pain. 2015;19(5):629–38.

    Article  CAS  PubMed  Google Scholar 

  55. Diochot S, Loret E, Bruhn T, Beress L, Lazdunski M. APETx1, a new toxin from the sea anemone Anthopleura elegantissima, blocks voltage-gated human ether-a-go-go-related gene potassium channels. Mol Pharmacol. 2003;64(1):59–69.

    Article  CAS  PubMed  Google Scholar 

  56. Izumi M, Ikeuchi M, Ji Q, Tani T. Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis. J Biomed Sci. 2012;19:77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Pierce KL, Premont RT, Lefkowitz RJ. Seven-transmembrane receptors. Nat Rev Mol Cell Biol. 2002;3(9):639–50.

    Article  CAS  PubMed  Google Scholar 

  58. De Falco L, Fioravanti A, Galeazzi M, Tenti S. Bradykinin and its role in osteoarthritis. Reumatismo. 2013;65(3):97–104.

    Article  PubMed  Google Scholar 

  59. Averbeck B, Rudolphi K, Michaelis M. Osteoarthritic mice exhibit enhanced prostaglandin E2 and unchanged calcitonin gene-related peptide release in a novel isolated knee joint model. J Rheumatol. 2004;31(10):2013–20.

    CAS  PubMed  Google Scholar 

  60. Flechtenmacher J, Talke M, Veith D. Bardykinin-receptor-inhibition-atherapeutic option in osteoarthritis? Osteoarthritis Cartilage. 2004;12 Suppl 137:abstract.

    Google Scholar 

  61. Song IH, Althoff CE, Hermann KG, Scheel AK, Knetsch T, Burmester GR, et al. Contrast-enhanced ultrasound in monitoring the efficacy of a bradykinin receptor 2 antagonist in painful knee osteoarthritis compared with MRI. Ann Rheum Dis. 2009;68(1):75–83.

    Article  CAS  PubMed  Google Scholar 

  62. Suri S, Gill SE, Massena de Camin S, Wilson D, McWilliams DF, Walsh DA. Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis. Ann Rheum Dis. 2007;66(11):1423–8.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Suri S, Walsh DA. Osteochondral alterations in osteoarthritis. Bone. 2012;51(2):204–11.

    Article  PubMed  Google Scholar 

  64. Russo AF. Calcitonin gene-related peptide (CGRP): a new target for migraine. Annu Rev Pharmacol Toxicol. 2015;55:533–52.

    Article  CAS  PubMed  Google Scholar 

  65. Bullock CM, Wookey P, Bennett A, Mobasheri A, Dickerson I, Kelly S. Peripheral calcitonin gene-related peptide receptor activation and mechanical sensitization of the joint in rat models of osteoarthritis pain. Arthritis Rheumatol. 2014;66(8):2188–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Benschop RJ, Collins EC, Darling RJ, Allan BW, Leung D, Conner EM, et al. Development of a novel antibody to calcitonin gene-related peptide for the treatment of osteoarthritis-related pain. Osteoarthritis Cartilage. 2014;22(4):578–85.

    Article  CAS  PubMed  Google Scholar 

  67. Steinhoff MS, von Mentzer B, Geppetti P, Pothoulakis C, Bunnett NW. Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease. Physiol Rev. 2014;94(1):265–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Goldstein DJ, Wang O, Todd LE, Gitter BD, DeBrota DJ, Iyengar S. Study of the analgesic effect of lanepitant in patients with osteoarthritis pain. Clin Pharmacol Ther. 2000;67(4):419–26.

    Article  CAS  PubMed  Google Scholar 

  69. Miller RJ, Jung H, Bhangoo SK, White FA. Cytokine and chemokine regulation of sensory neuron function. Handb Exp Pharmacol. 2009;194:417–49.

    Article  CAS  Google Scholar 

  70. Belmadani A, Tran PB, Ren D, Assimacopoulos S, Grove EA, Miller RJ. The chemokine stromal cell-derived factor-1 regulates the migration of sensory neuron progenitors. J Neurosci. 2005;25(16):3995–4003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Abbadie C, Bhangoo S, De Koninck Y, Malcangio M, Melik-Parsadaniantz S, White FA. Chemokines and pain mechanisms. Brain Res Rev. 2009;60(1):125–34.

    Article  CAS  PubMed  Google Scholar 

  72. Abbadie C, Lindia JA, Cumiskey AM, Peterson LB, Mudgett JS, Bayne EK, et al. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc Natl Acad Sci U S A. 2003;100(13):7947–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Miller RE, Tran PB, Das R, Ghoreishi-Haack N, Ren D, Miller RJ, et al. CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(50):20602–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. McDougall JJ, Muley MM. The role of proteases in pain. Handb Exp Pharmacol. 2015;227:239–60.

    Article  CAS  PubMed  Google Scholar 

  75. Russell FA, Schuelert N, Veldhoen VE, Hollenberg MD, McDougall JJ. Activation of PAR(2) receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint. Br J Pharmacol. 2012;167(8):1665–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Russell FA, Veldhoen VE, Tchitchkan D, McDougall JJ. Proteinase-activated receptor-4 (PAR4) activation leads to sensitization of rat joint primary afferents via a bradykinin B2 receptor-dependent mechanism. J Neurophysiol. 2010;103(1):155–63.

    Article  CAS  PubMed  Google Scholar 

  77. Pellett S, Yaksh TL, Ramachandran R. Current status and future directions of botulinum neurotoxins for targeting pain processing. Toxins (Basel). 2015;7(11):4519–63.

    Article  CAS  Google Scholar 

  78. La Porta C, Bura SA, Negrete R, Maldonado R. Involvement of the endocannabinoid system in osteoarthritis pain. Eur J Neurosci. 2014;39(3):485–500.

    Article  PubMed  Google Scholar 

  79. Miller RE, Miller RJ, Malfait AM. Osteoarthritis joint pain: the cytokine connection. Cytokine. 2014;70(2):185–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Maksymowych WP, Russell AS, Chiu P, Yan A, Jones N, Clare T, et al. Targeting tumour necrosis factor alleviates signs and symptoms of inflammatory osteoarthritis of the knee. Arthritis Res Ther. 2012;14(5):R206.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Chevalier X, Ravaud P, Maheu E, Baron G, Rialland A, Vergnaud P, et al. Adalimumab in patients with hand osteoarthritis refractory to analgesics and NSAIDs: a randomised, multicentre, double-blind, placebo-controlled trial. Ann Rheum Dis. 2015;74(9):1697–705.

    Article  CAS  PubMed  Google Scholar 

  82. Chevalier X, Goupille P, Beaulieu AD, Burch FX, Bensen WG, Conrozier T, et al. Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2009;61(3):344–52.

    Article  CAS  PubMed  Google Scholar 

  83. Lacy SE, Wu C, Ambrosi DJ, Hsieh CM, Bose S, Miller R, et al. Generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig(TM)) molecule that specifically and potently neutralizes both IL-1alpha and IL-1beta. MAbs. 2015;7(3):605–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Vachon-Presseau E, Centeno MV, Ren W, Berger SE, Tetreault P, Ghantous M, et al. The emotional brain as a predictor and amplifier of chronic pain. J Dent Res. 2016.

Download references

Acknowledgments

A.M. Malfait (R01AR060364 and R01AR064251) and R.J. Miller (R01AR064251) acknowledge the support by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center, 1611 W Harrison Street, Suite 510, Chicago, IL, 60612, USA

    Anne-Marie Malfait

  2. Department of Pharmacology, Northwestern University, Robert H. Lurie Medical Research Center, 303 E. Superior, Chicago, IL, 60613, USA

    Richard J. Miller

Authors
  1. Anne-Marie Malfait
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard J. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne-Marie Malfait.

Ethics declarations

Conflict of Interest

Anne-Marie Malfait and Richard J. Miller declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human subjects performed by any of the authors. Animal studies performed by the authors were approved by the Institutional Animal Care and Use Committee at Rush University Medical Center and at Northwestern University.

Additional information

This article is part of the Topical Collection on Bone and Joint Pain

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Malfait, AM., Miller, R.J. Emerging Targets for the Management of Osteoarthritis Pain. Curr Osteoporos Rep 14, 260–268 (2016). https://doi.org/10.1007/s11914-016-0326-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11914-016-0326-z

Keywords

Search

Navigation