In Search of the Etiology of Anterior Knee Pain



Because pain is often the only manifest symptom in patients suffering from anterior knee pain (AKP), an in-depth analysis of this subjective emotion may yield valuable information about this elusive knee condition. This book chapter focuses on pain perception and its mechanisms, physiology, and evolutionary context. In the last 10 years, new insights have contributed to our understanding of pain. Those that focus on pain and the role of homeostatic tissue regulation and are related to AKP will be discussed.


Neuropathic Pain Irritable Bowel Syndrome Acute Inflammation Mechanical Allodynia Inflammatory Pain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1.  1.
    Abbas AK, Lichtman AH. Basic Immunology: Functions and Disorders of the Immune System. Philadelphia: Saunders Elsevier; 2007.Google Scholar
  2.  2.
    Albertazzi P, Steel SA, Botazzi M. Effect of intermittent compression therapy on bone mineral density in women with low bone mass. Bone. 2005;37:662-668.PubMedCrossRefGoogle Scholar
  3.  3.
    Alfredson H. The chronic painful Achilles and patellar tendon: research on basic biology and treatment. Scand J Med Sci Sports. 2005;15:252-259.PubMedCrossRefGoogle Scholar
  4.  4.
    Andersson HI, Ejlertsson G, Leden I, et al. Chronic pain in a geographically defined general population: studies of different age, gender, social class, and pain location. Clin J Pain. 1993;9:174-182.PubMedCrossRefGoogle Scholar
  5.  5.
    Apkarian AV, Baliki MN, Geha PY. Towards a theory of chronic pain. Prog Neurobiol. 2009;87:81-97.PubMedCrossRefGoogle Scholar
  6.  6.
    Beaulé PE, Campbell P, Lu Z, et al. Vascularity of the arthritic femoral head and hip resurfacing. J Bone Joint Surg. 2006;88-A(Suppl 4):85-96.CrossRefGoogle Scholar
  7.  7.
    Ben-Eliyahu D. Infrared thermographic imaging in the detection of sympathetic dysfunction in patients with patellofemoral pain syndrome. J Manipulative Physiol Ther. 1992;3:164-170.Google Scholar
  8.  8.
    Bingel U, Tracey I. Imaging CNS modulation of pain in humans. Physiology. 2008;23:371-380.PubMedCrossRefGoogle Scholar
  9.  9.
    Bizzini M, Childs JD, Piva SR, et al. Systematic review of the quality of randomized controlled trials for patellofemoral pain syndrome. J Orthop Sports Phys Ther. 2003;33:4-20.PubMedGoogle Scholar
  10. 10.
    Brookes M, Revell WJ. Blood Supply of Bone. London: Springer; 1998.Google Scholar
  11. 11.
    Brushøj C, Henriksen BM, Albrecht-Beste E, et al. Acute patellofemoral pain: aggravating activities, clinical examination, MRI and ultrasound findings. Br J Sports Med. 2008; 42:64-67.PubMedCrossRefGoogle Scholar
  12. 12.
    Butler-Manuel PA. Sympathetically mediated anterior knee pain. Acta Orthop Scand. 1992;63:90-93.PubMedCrossRefGoogle Scholar
  13. 13.
    Callaghan MJ, Selfe J, McHenry A, et al. Effects of patellar taping on knee joint proprioception in patients with patellofemoral pain syndrome. Man Ther. 2008;13:192-199.PubMedCrossRefGoogle Scholar
  14. 14.
    Carlsson AM, Werner S, Mattlar CE, et al. Personality in patients with long-term patellofemoral pain syndrome. Knee Surg Sports Traumatol Arthrosc. 1993;1:178-183.PubMedCrossRefGoogle Scholar
  15. 15.
    Colleran NP, Wilkerson MK, Bloomfield SA, et al. Alterations in skeletal perfusion with simulated microgravity: a possible mechanism for bone remodeling. J Appl Physiol. 2000;89:1046-1054.PubMedGoogle Scholar
  16. 16.
    Conaghan PG, Vanharanta H, Dieppe PA. Is progressive osteoarthritis an atheromatous vascular disease? Ann Rheum Dis. 2005;64:1539-1541.PubMedCrossRefGoogle Scholar
  17. 17.
    Craig AD. A new view of pain as a homeostatic emotion. Trends Neurosci. 2003;26:303-307.PubMedCrossRefGoogle Scholar
  18. 18.
    Dieppe PA, Lohmander S. Pathogenesis and management of pain in osteoarthritis. Lancet. 2005;365:965-973.PubMedCrossRefGoogle Scholar
  19. 19.
    Dixit S, DiFiori JP, Burton M, et al. Management of patellofemoral pain syndrome. Am Fam Physician. 2007;75:194-202.PubMedGoogle Scholar
  20. 20.
    Dye SF. The pathophysiology of patellofemoral pain. Clin Orthop Relat Res. 2005;436:100-110.PubMedCrossRefGoogle Scholar
  21. 21.
    Dye SF, Chew MH. The use of scintigraphy to detect increased osseous metabolic activity about the knee. J Bone Joint Surg. 1993;75:1388-1406.Google Scholar
  22. 22.
    Dye SF, Vaupel GL, Dye CC. Conscious neurosensory mapping of the internal structures of the human knee without intraarticular anesthesia. Am J Sports Med. 1998;26:773-777.PubMedGoogle Scholar
  23. 23.
    Fearon I, McGrath PJ, Achat H. ‘Booboos’: the study of everyday pain among children. Pain. 1996;68:55-62.PubMedCrossRefGoogle Scholar
  24. 24.
    Firestein GS, Corr M. Common mechanisms in immune-mediated inflammatory disease. J Rheumatol. 2005;32(Suppl 73):8-13.Google Scholar
  25. 25.
    Forsgren S, Grimsholm O, Jönsson M, et al. New insight into the non-neuronal cholinergic system via studies on chronically painful tendons and inflammatory situations. Life Sci. 2009;84:865-870.PubMedCrossRefGoogle Scholar
  26. 26.
    Frost HM. A 2003 update of bone physiology and Wolff’’s law for clinicians. Angle Orthod. 2004;74:3-15.PubMedGoogle Scholar
  27. 27.
    Fulkerson JP et al. Disorders of the Patellofemoral Joint. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2004.Google Scholar
  28. 28.
    Gross PM, Marcus ML, Heistad DD. Measurements of blood flow to bone and marrow in experimental animals by means of the microsphere technique. J Bone Joint Surg. 1981;6: 1028-1031.Google Scholar
  29. 29.
    Gross TS, Damji AA, Judex S, et al. Bone hyperemia precedes disuse-induced intracortical bone resorption. J Appl Physiol. 1999;86:230-235.PubMedCrossRefGoogle Scholar
  30. 30.
    Gross TS, Poliachik SL, Ausk BJ, et al. Why rest stimulates bone formation: a hypothesis based on complex adaptive phenomenon. Exerc Sport Sci Rev. 2004;32:9-13.PubMedCrossRefGoogle Scholar
  31. 31.
    Hasselström J, Liu-Palmgren J, Rasjö-Wrååk G. Prevalence of pain in general practice. Eur J Pain. 2002;6:375-385.PubMedCrossRefGoogle Scholar
  32. 32.
    Heintjes E, Berger MY, Bierma-Zeinstra SM, et al (2004) Pharmacotherapy for patellofemoral pain syndrome. Cochrane Database Syst Rev. 3: CD003470.Google Scholar
  33. 33.
    Higgins DF, Kimura K, Iwano M, et al. Hypoxia-inducible factor signaling in the development of tissue fibrosis. Cell Cycle. 2008;7:1128-1132.PubMedCrossRefGoogle Scholar
  34. 34.
    Jensen R, Hystad T, Barheim A. Knee function and pain related to psychological variables in patients with long-term patellofemoral pain syndrome. J Orthop Sports Phys Ther. 2005;35:594-600.PubMedGoogle Scholar
  35. 35.
    Jensen R, Kvale A, Baerheim A. Is patellofemoral pain neuropathic? Clin J Pain. 2008;24:384-394.PubMedCrossRefGoogle Scholar
  36. 36.
    Kalliokoski KK, Kemppainen J, Larmola K, et al. Muscle blood flow and flow heterogeneity during exercise studied with positron emission tomography in humans. Eur J Appl Physiol. 2000;83:395-401.PubMedCrossRefGoogle Scholar
  37. 37.
    Kannus P, Natri A, Paakkala T, et al. An outcome study of chronic patellofemoral pain syndrome. Seven-year follow-up of patients in a randomized, controlled trial. J Bone Joint Surg. 1999;81-A:355-363.Google Scholar
  38. 38.
    Kirschner MH, Menck J, Nerlich A, et al. The arterial blood supply of the human patella. Its clinical importance for the operating technique in vascularized knee joint transplantations. Surg Radiol Anat. 1997;19:345-351.PubMedCrossRefGoogle Scholar
  39. 39.
    Kogianni G, Mann V, Noble BS. Apoptotic bodies convey activity capable of initiating osteoclastogenesis and localized bone destruction. J Bone Miner Res. 2008;6:915-927.CrossRefGoogle Scholar
  40. 40.
    Libby P. Inflammation in atherosclerosis. Nature. 2002; 420:868-874.PubMedCrossRefGoogle Scholar
  41. 41.
    Loeser JD, Treede RD. The Kyoto protocol of IASP basic pain terminology. Pain. 2008;137:473-477.PubMedCrossRefGoogle Scholar
  42. 42.
    Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol. 2005;32(Suppl 75):6-21.Google Scholar
  43. 43.
    MelzackP Wall P. Textbook of Pain. 4th ed. London: Harcourt Publishers Limited; 2000.Google Scholar
  44. 44.
    Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8:958-969.PubMedCrossRefGoogle Scholar
  45. 45.
    Näslund J, Näslund UB, Odenbring S, et al. Sensory stimulation (acupuncture) for the treatment of idiopathic anterior knee pain. J Rehabil Med. 2002;34:231-238.PubMedCrossRefGoogle Scholar
  46. 46.
    Näslund J, Odenbring S, Näslund UB, et al. Diffusely increased bone scintigraphic uptake in patellofemoral pain syndrome. Br J Sports Med. 2005;39:162-165.PubMedCrossRefGoogle Scholar
  47. 47.
    Näslund J, Waldén M, Lindberg LG. Decreased pulsatile blood flow in the patella in patellofemoral pain. Am J Sports Med. 2007;35:1668-1673.PubMedCrossRefGoogle Scholar
  48. 48.
    Noble B. Microdamage and apoptosis. Eur J Morphol. 2005;42:91-98.PubMedCrossRefGoogle Scholar
  49. 49.
    Olausson HW, Cole J, Vallbo A, et al. Unmyelinated tactile afferents have opposite effects on insular and somatosensory cortical processing. Neurosci Lett. 2008;436:128-132.PubMedCrossRefGoogle Scholar
  50. 50.
    Otter MW, Qin YX, Rbin CT, et al. Does bone perfusion/reperfusion initiate bone remodeling and the stress fracture syndrome? Med Hypotheses. 1999;53:363-368.PubMedCrossRefGoogle Scholar
  51. 51.
    Pennisi P, Signorelli SS, Riccoben S, et al. Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels. Osteoporos Int. 2004;15:389-395.PubMedCrossRefGoogle Scholar
  52. 52.
    Ryles MT, Pilmanis AA. The initial signs and symptoms of altitude decompression sickness. Aviat Space Environ Med. 1996;10:983-989.Google Scholar
  53. 53.
    Sanchis-Alfonso V. Patellofemorale schmerzen. Orthopade. 2008;37:835-840.PubMedCrossRefGoogle Scholar
  54. 54.
    Sanchis-Alfonso V, Roselló-Sastre E, Subías-Lopez A. Neuroanatomic basis for pain in patellar tendinosis (“jumper’s knee”): a neuroimmunohistochemical study. Am J Knee Surg. 2001;14:174-177.PubMedGoogle Scholar
  55. 55.
    Sandberg M, Zhang Q, Styf J, et al. Non-invasive monitoring of muscle blood perfusion by photoplethysmography: evaluation of a new application. Acta Physiol Scand. 2005;183:335-343.PubMedCrossRefGoogle Scholar
  56. 56.
    Scott A, Khan KM, Roberts R, et al. What do we mean by the term “inflammation”? A contemporary basic science update for sports medicine. Br J Sports Med. 2004;38:372-380.PubMedCrossRefGoogle Scholar
  57. 57.
    Selfe J, Harper L, Pedersen I, et al. Cold legs: a potential indicator of negative outcome in the rehabilitation of patients with patellofemoral pain syndrome. Knee. 2003;10:139-143.PubMedCrossRefGoogle Scholar
  58. 58.
    Selfe J, Karki A, Stevens D. A review of the role of circulatory deficit in the genesis of patellofemoral pain. Phys Ther Rev. 2002;7:169-172.CrossRefGoogle Scholar
  59. 59.
    Shim SS, Patterson FP. A direct method of qualitative study of bone blood circulation. Surg Gynecol Obstet. 1967;125: 261-268.Google Scholar
  60. 60.
    Soe HS, Kim HW, Roh DH, et al. A new rat model for thrombus-induced ischemic pain (TIIP); development of bilateral mechanical allodynia. Pain. 2008;139:520-532.CrossRefGoogle Scholar
  61. 61.
    Thomee P, Thomee R, Karlsoon J. Patellofemoral pain syndrome: pain, coping strategies and degree of well-being. Scand J Med Sci Sports. 2002;12:276-281.PubMedCrossRefGoogle Scholar
  62. 62.
    Trueta J. The role of the vessels in osteogenesis. J Bone Joint Surg. 1963;45-B:402-418.Google Scholar
  63. 63.
    Vodovotz Y, Constantine G, Rubin J, et al. Mechanistic stimulation of inflammation: current state and future prospects. Math Biosci. 2009;217:1-10.PubMedCrossRefGoogle Scholar
  64. 64.
    Wang L, Fritton SP, Weinbaum S, et al. On bone adaption due to venous stasis. J Biomech. 2003;36:1439-1451.PubMedCrossRefGoogle Scholar
  65. 65.
    Weerakkody NS, Percival P, Hickey MW, et al. Effects of local pressure and vibration on muscle pain from eccentric exercise and hypertonic saline. Pain. 2003;105:425-435.PubMedCrossRefGoogle Scholar
  66. 66.
    Wenger RH, Stiehl DP, Camenisch G. Integration of oxygen signaling at the consensus HRE. Sci STKE. 2005;2005(306): re12.PubMedCrossRefGoogle Scholar
  67. 67.
    Whitney C, Warburton D, Frohlich J, et al. Are cardiovascular disease and osteoporosis directly linked? Sports Med. 2004;34:779-807.PubMedCrossRefGoogle Scholar
  68. 68.
    Witonski D. Anterior knee pain syndrome. Int Orthop. 1999;23:341-344.PubMedCrossRefGoogle Scholar
  69. 69.
    Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med. 2004;140:441-451.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2011

Authors and Affiliations

  1. 1.Department of Physiology and PharmacologyKarolinska InstituteStockholmSweden

Personalised recommendations