Involvement of the endocannabinoid system in osteoarthritis pain

European Journal of Neuroscience

Volumn 39, Issue 3, 2014, Pages 485-500

  La Porta, Carmen ^a   Bura, Simona A ^a   Negrete, Roger ^a   Maldonado, Rafael ^a  

^a UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

Author keywords

Analgesia; Cannabinoid; Nociception; Osteoarthritis; Pain

Indexed keywords

ANALGESIA; CANNABINOID; NOCICEPTION; OSTEOARTHRITIS; PAIN;

ANIMALS; CANNABINOID RECEPTOR AGONISTS; CANNABINOIDS; HUMANS; OSTEOARTHRITIS; PAIN;

EID: 84893363562     PISSN: 0953816X     EISSN: 14609568     Source Type: Journal    
DOI: 10.1111/ejn.12468     Document Type: Article

References (194)

1. Agarwal, N., Pacher, P., Tegeder, I., Amaya, F., Constantin, C.E., Brenner, G.J., Rubino, T., Michalski, C.W., Marsicano, G., Monory, K., Mackie, K., Marian, C., Batkai, S., Parolaro, D., Fischer, M.J., Reeh, P., Kunos, G., Kress, M., Lutz, B., Woolf, C.J. & Kuner, R. (2007) Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors. Nat. Neurosci., 10, 870-879.
2. Ahern, B.J., Parvizi, J., Boston, R. & Schaer, T.P. (2009) Preclinical animal models in single site cartilage defect testing: a systematic review. Osteoarthr. Cartilage, 17, 705-713.
3. Ahn, K., Smith, S.E., Liimatta, M.B., Beidler, D., Sadagopan, N., Dudley, D.T., Young, T., Wren, P., Zhang, Y., Swaney, S., Van Becelaere, K., Blankman, J.L., Nomura, D.K., Bhattachar, S.N., Stiff, C., Nomanbhoy, T.K., Weerapana, E., Johnson, D.S. & Cravatt, B.F. (2011) Mechanistic and pharmacological characterization of PF-04457845: a highly potent and selective FAAH inhibitor that reduces inflammatory and noninflammatory pain. J. Pharmacol. Exp. Ther., 338, 114-124.
4. Akhtar, N. & Haqqi, T.M. (2012) Current nutraceuticals in the management of osteoarthritis: a review. Ther. Adv. Musculoskelet. Dis., 4, 181-207.
5. Anand, U., Otto, W.R., Sanchez-Herrera, D., Facer, P., Yiangou, Y., Korchev, Y., Birch, R., Benham, C., Bountra, C., Chessell, I.P. & Anand, P. (2008) Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons. Pain, 138, 667-680.
6. Aupperle, K.R., Boyle, D.L., Hendrix, M., Seftor, E.A., Zvaifler, N.J., Barbosa, M. & Firestein, G. (1998) Regulation of synoviocyte proliferation, apoptosis, and invasion by the p53 tumor suppressor gene. Am. J. Pathol., 152, 1091-1098.
7. Baker, D., Pryce, G., Davies, W.L. & Hiley, C.R. (2006) In silico patent searching reveals a new cannabinoid receptor. Trends Pharmacol. Sci., 27, 1-4.
8. Baliki, M.N., Geha, P.Y., Jabakhanji, R., Harden, N., Schnitzer, T.J. & Apkarian, A.V. (2008) A preliminary fMRI study of analgesic treatment in chronic back pain and knee osteoarthritis. Mol. Pain, 4, 47.
9. Bendele, A.M. (2001) Animal models of osteoarthritis. J. Musculoskelet. Neuronal Interact., 1, 363-376.
10. Bendele, A.M., Bendele, R.A., Hulman, J.F. & Swann, B.P. (1996) Effets bénéfiques d'un traitement par la diacerhéine chez des cobayes atteints d'arthrose. Rev. Praticien, 46, 35-39.
11. Bermudez-Silva, F.J., Suarez, J., Baixeras, E., Cobo, N., Bautista, D., Cuesta-Munoz, A.L., Fuentes, E., Juan-Pico, P., Castro, M.J., Milman, G., Mechoulam, R., Nadal, A. & Rodriguez de Fonseca, F. (2008) Presence of functional cannabinoid receptors in human endocrine pancreas. Diabetologia, 51, 476-487.
12. Bingham, C.O., Buckland-Wright, J.C., Garnero, P., Cohen, S.B., Dougados, M., Adami, S., Clauw, D.J., Spector, T.D., Pelletier, J.-P., Raynauld, J.-P., Strand, V., Simon, L.S., Meyer, J.M., Cline, G.A. & Beary, J.F. (2006) Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum., 54, 3494-3507.
13. Bisogno, T. & Di Marzo, V. (2010) Cannabinoid receptors and endocannabinoids: role in neuroinflammatory and neurodegenerative disorders. CNS Neurol. Disord. Dr., 9, 564-573.
14. Blake, D.R., Robson, P., Ho, M., Jubb, R.W. & McCabe, C.S. (2006) Preliminary assessment of the efficacy, tolerability and safety of a cannabisbased medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford), 45, 50-52.
15. Brandt, K.D., Mazzuca, S.A., Katz, B.P., Lane, K.A., Buckwalter, K.A., Yocum, D.E., Wolfe, F., Schnitzer, T.J., Moreland, L.W., Manzi, S., Bradley, J.D., Sharma, L., Oddis, C.V., Hugenberg, S.T. & Heck, L.W. (2005) Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial. Arthritis Rheum., 52, 2015-2025.
16. Bridges, D., Rice, A.S., Egertova, M., Elphick, M.R., Winter, J. & Michael, G.J. (2003) Localisation of cannabinoid receptor 1 in rat dorsal root ganglion using in situ hybridisation and immunohistochemistry. Neuroscience, 119, 803-812.
17. Bronstein, K., Dhaliwal, J. & Leider, H. (2011) Rates of inappropriate drug use in the chronic pain population: an update. J. Pain, 12, 5.
18. Buckwalter, J.A. & Mankin, H.J. (1998) Articular cartilage repair and transplantation. Arthritis Rheum., 41, 1331-1342.
19. Buckwalter, J.A. & Martin, J.A. (2006) Osteoarthritis. Adv. Drug Deliver. Rev., 58, 150-167.
20. Bura, A.S., Guegan, T., Zamanillo, D., Vela, J.M. & Maldonado, R. (2013) Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain. Eur. J. Pain, 17, 832-843.
21. Butler, S.H., Weil-Fugazza, J., Godefroy, F. & Besson, J.M. (1985) Reduction of arthritis and pain behaviour following chronic administration of amitriptyline or imipramine in rats with adjuvant-induced arthritis. Pain, 23, 159-175.
22. Calignano, A., La Rana, G., Makriyannis, A., Lin, S.Y., Beltramo, M. & Piomelli, D. (1997) Inhibition of intestinal motility by anandamide, an endogenous cannabinoid. Eur. J. Pharmacol., 340, R7-R8.
23. Castañé, A., Célérier, E., Martín, M., Ledent, C., Parmentier, M., Maldonado, R. & Valverde, O. (2006) Development and expression of neuropathic pain in CB1 knockout mice. Neuropharmacology, 50, 111-122.
24. Chandran, P., Pai, M., Blomme, E.A., Hsieh, G.C., Decker, M.W. & Honore, P. (2009) Pharmacological modulation of movement-evoked pain in a rat model of osteoarthritis. Eur. J. Pharmacol., 613, 39-45.
25. Chapman, V. (2013) Role of endocannabinoid signaling in the control of pain. Proceeding of the British Pharmacologzeical Society, 6th European Workshop on Cannabinoid Research, Trinity College Dublin, Ireland, 18-20 April 2013, S008.
26. Chappell, A.S., Desaiah, D., Liu-Seifert, H., Zhang, S., Skljarevski, V., Belenkov, Y. & Brown, J.P. (2011) A double-blind, randomized, placebo-controlled study of the efficacy and safety of duloxetine for the treatment of chronic pain due to osteoarthritis of the knee. Pain Pract., 11, 33-41.
27. Childers, S.R. & Deadwyler, S.A. (1996) Role of cyclic AMP in the actions of cannabinoid receptors. Biochem. Pharmacol., 52, 819-827.
28. Chockalingam, P.S., Sun, W., Rivera-Bermudez, M.A., Zeng, W., Dufield, D.R., Larsson, S., Lohmander, L.S., Flannery, C.R., Glasson, S.S., Georgiadis, K.E. & Morris, E.A. (2011) Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor. Osteoarthr. Cartilage, 19, 315-323.
29. Chubinskaya, S., Hurtig, M. & Rueger, D.C. (2007) OP-1/BMP-7 in cartilage repair. Int. Orthop., 31, 773-781.
30. Clapper, J.R., Moreno-Sanz, G., Russo, R., Guijarro, A., Vacondio, F., Duranti, A., Tontini, A., Sanchini, S., Sciolino, N.R., Spradley, J.M., Hohmann, A.G., Calignano, A., Mor, M., Tarzia, G. & Piomelli, D. (2010) Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nat. Neurosci., 13, 1265-1270.
31. Compton, D.R., Dewey, W.L. & Martin, B.R. (1990) Cannabis dependence and tolerance production. Adv. Alcohol Subst. Abuse, 9, 129-147.
32. Cota, D., Genghini, S., Pasquali, R. & Pagotto, U. (2003a) Antagonizing the cannabinoid receptor type 1: a dual way to fight obesity. J. Endocrinol. Invest., 26, 1041-1044.
33. Cota, D., Marsicano, G., Tschop, M., Grubler, Y., Flachskamm, C., Schubert, M., Auer, D., Yassouridis, A., Thone-Reineke, C., Ortmann, S., Tomassoni, F., Cervino, C., Nisoli, E., Linthorst, A.C., Pasquali, R., Lutz, B., Stalla, G.K. & Pagotto, U. (2003b) The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J. Clin. Invest., 112, 423-431.
34. Davies, P.S., Graham, S.M., MacFarlane, R.J., Leonidou, A., Mantalaris, A. & Tsiridi, E. (2013) Disease-modifying osteoarthritis drugs: in vitro and in vivo data on the development of DMOADs under investigation. Expert Opin. Inv. Drug., 22, 423-441.
35. Devane, W.A., Hanus, L., Breuer, A., Pertwee, R.G., Stevenson, L.A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A. & Mechoulam, R. (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 258, 1946-1949.
36. Dewey, W.L. (1986) Cannabinoid pharmacology. Pharmacol. Rev., 38, 151-178.
37. Di Marzo, V. (2012) Inhibitors of endocannabinoid breakdown for pain: not so FA(AH)cile, after all. Pain, 153, 1785-1786.
38. Di Marzo, V., Fontana, A., Cadas, H., Schinelli, S., Cimino, G., Schwartz, J.C. & Piomelli, D. (1994) Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature, 372, 686-691.
39. Dinh, T.P., Freund, T.F. & Piomelli, D. (2002) A role for monoglyceride lipase in 2- arachidonoylglycerol inactivation. Chem. Phys. Lipids, 121, 149-158.
40. Dougados, M., Nguyen, M., Berdah, L., Maziéres, B., Vignon, E. & Lequesne, M. (2001) Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation of the Chondromodulating Effect of Diacerein in OA of the Hip. Arthritis Rheum., 44, 2539-2547.
41. Drew, L.J., Harris, J., Millns, P.J., Kendall, D.A. & Chapman, V. (2000) Activation of spinal cannabinoid 1 receptors inhibits C-fibre driven hyperexcitable neuronal responses and increases [35S]GTPgammaS binding in the dorsal horn of the spinal cord of noninflamed and inflamed rats. Eur. J. Neurosci., 12, 2079-2086.
42. Ernst, E. (2003) Avocado-soybean unsaponifiables (ASU) for osteoarthritis - a systematic review. Clin. Rheumatol., 22, 285-288.
43. Farrell, M., Gibson, S., McMeeken, J. & Helme, R. (2000) Pain and hyperalgesia in osteoarthritis of the hands. J. Rheumatol., 27, 441-447.
44. Felson, D.T., Lawrence, R.C., Dieppe, P.A., Hirsch, R., Helmick, C.G., Jordan, J.M., Kington, R.S., Lane, N.E., Nevitt, M.C., Zhang, Y., Sowers, M., McAlindon, T., Spector, T.D., Poole, A.R., Yanovski, S.Z., Ateshian, G., Sharma, L., Buckwalter, J.A., Brandt, K.D. & Fries, J.F. (2000) Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann. Intern. Med., 133, 635-646.
45. Fernihough, J., Gentry, C., Malcangio, M., Fox, A., Rediske, J., Pellas, T., Kidd, B., Bevan, S. & Winter, J. (2004) Pain related behaviour in two models of osteoarthritis in the rat knee. Pain, 112, 83-93.
46. Fields, H.L., Heinricher, M.M. & Mason, P. (1991) Neurotransmitters in nociceptive modulatory circuits. Annu. Rev. Neurosci., 14, 219-245.
47. Fitzcharles, M.A., McDougall, J., Ste-Marie, P.A. & Padjen, I. (2012) Clinical implications for cannabinoid use in the rheumatic diseases: potential for help or harm? Arthritis Rheum., 64, 2417-2425.
48. Frank, R.G., Kashani, J.H., Parker, J.C., Beck, N.C., Brownlee-Duffeck, M., Elliott, T.R., Haut, A.E., Atwood, C., Smith, E. & Kay, D.R. (1988) Antidepressant analgesia in rheumatoid arthritis. J. Rheumatol., 15, 1632-1638.
49. Furuse, S., Kawamata, T., Yamamoto, J., Niiyama, Y., Omote, K. & Watanabe, M. (2009) Reduction of bone cancer pain by activation of spinal cannabinoid receptor 1 and its expression in the superficial dorsal horn of the spinal cord in a murine model of bone cancer pain. Anesthesiology, 111, 173-186.
50. Galiegue, S., Mary, S., Marchand, J., Dussossoy, D., Carriere, D., Carayon, P., Bouaboula, M., Shire, D., Le Fur, G. & Casellas, P. (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur. J. Biochem., 232, 54-61.
51. Gerard, C.M., Mollereau, C., Vassart, G. & Parmentier, M. (1991) Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem. J., 279, 129-134.
52. Grotenhermen, F. (2004) Pharmacology of cannabinoids. Neuro. Endocrinol. Lett., 25, 14-23.
53. Grotenhermen, F. (2005) Cannabinoids. Curr. Drug Targets CNS Neurol. Disord., 4, 507-530.
54. Guindon, J. & Hohmann, A.G. (2009) The endocannabinoid system and pain. CNS Neurol. Disord. Dr., 8, 403-421.
55. Guingamp, C., Gegout-Pottie, P., Philippe, L., Terlain, B., Netter, P. & Gillet, P. (1997) Mono-iodoacetate-induced experimental osteoarthritis: a dose-response study of loss of mobility, morphology, and biochemistry. Arthritis Rheum., 40, 1670-1679.
56. Gutierrez, T., Crystal, J.D., Zvonok, A.M., Makriyannis, A. & Hohmann, A.G. (2011) Selfmedication of a cannabinoid CB(2) agonist in an animal model of neuropathic pain. Pain, 152, 1976-1987.
57. Harvey, V.L. & Dickenson, A.H. (2009) Behavioural and electrophysiological characterisation of experimentally induced osteoarthritis and neuropathy in C57Bl/6 mice. Mol. Pain, 5, 18.
58. Haseeb, A. & Haqqi, T.M. (2013) Immunopathogenesis of osteoarthritis. Clin. Immunol., 146, 185-196.
59. Hellio le Graverand, M.P., Clemmer, R.S., Redifer, P., Brunell, R.M., Hayes, C.W., Brandt, K.D., Abramson, S.B., Manning, P.T., Miller, C.G. & Vignon, E. (2013) A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee. Ann. Rheum. Dis., 72, 187-195.
60. Henrotin, Y.E., Bruckner, P. & Pujol, J.P. (2003) The role of reactive oxygen species in homeostasis and degradation of cartilage. Osteoarthr. Cartilage, 11, 747-755.
61. Herkenham, M., Lynn, A.B., Johnson, M.R., Melvin, L.S., de Costa, B.R. & Rice, K.C. (1991) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J. Neurosci., 11, 563-583.
62. Hoegh-Andersen, P., Tanko, L.B., Andersen, T.L., Lundberg, C.V., Mo, J.A., Heegaard, A.M., Delaisse, J.M. & Christgau, S. (2004) Ovariectomized rats as a model of postmenopausal osteoarthritis: validation and application. Arthritis Res. Ther., 6, R169-R180.
63. Hohmann, A.G. (2002) Spinal and peripheral mechanisms of cannabinoid antinociception: behavioral, neurophysiological and neuroanatomical perspectives. Chem. Phys. Lipids, 121, 173-190.
64. Hohmann, A.G. & Herkenham, M. (1999) Localization of central cannabinoid CB1 receptor messenger RNA in neuronal subpopulations of rat dorsal root ganglia: a double-label in situ hybridization study. Neuroscience, 90, 923-931.
65. Huggins, J.P., Smart, T.S., Langman, S., Taylor, L. & Young, T. (2012) An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee. Pain, 153, 1837-1846.
66. Hunter, D.J. (2011) Pharmacologic therapy for osteoarthritis-the era of disease modification. Nat. Rev. Rheumatol., 7, 13-22.
67. Hunter, D.J., Pike, M.C., Jonas, B.L., Kissin, E., Krop, J. & McAlindon, T. (2010) Phase 1 safety and tolerability study of BMP-7 in symptomatic knee osteoarthritis. BMC Musculoskel. Dis., 11, 232.
68. Hwa, S.Y., Burkhardt, D., Little, C. & Ghosh, P. (2001) The effects of orally administered diacerein on cartilage and subchondral bone in an ovine model of osteoarthritis. J. Rheumatol., 28, 825-834.
69. Ibrahim, M.M., Porreca, F., Lai, J., Albrecht, P.J., Rice, F.L., Khodorova, A., Davar, G., Makriyannis, A., Vanderah, T.W., Mata, H.P. & Malan, T.P. Jr. (2005) CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc. Natl. Acad. Sci. USA, 102, 3093-3098.
70. Idris, A.I. & Ralston, S.H. (2012) Role of cannabinoids in the regulation of bone remodeling. Front. Endocrinol. (Lausanne), 3, 136.
71. Ishac, E.J., Jiang, L., Lake, K.D., Varga, K., Abood, M.E. & Kunos, G. (1996) Inhibition of exocytotic noradrenaline release by presynaptic cannabinoid CB1 receptors on peripheral sympathetic nerves. Brit. J. Pharmacol., 118, 2023-2028.
72. Ivanavicius, S.P., Ball, A.D., Heapy, C.G., Westwood, F.R., Murray, F. & Read, S.J. (2007) Structural pathology in a rodent model of osteoarthritis is associated with neuropathic pain: increased expression of ATF-3 and pharmacological characterisation. Pain, 128, 272-282.
73. Janusz, M.J., Hookfin, E.B., Heitmeyer, S.A., Woessner, J.F., Freemont, A.J., Hoyland, J.A., Brown, K.K., Hsieh, L.C., Almstead, N.G., De, B., Natchus, M.G., Pikul, S. & Taiwo, Y.O. (2001) Moderation of iodoacetate-induced experimental osteoarthritis in rats by matrix metalloproteinase inhibitors. Osteoarthr. Cartilage, 9, 751-760.
74. Johnson, D.R., Stebulis, J.A., Rossetti, R.G., Burstein, S.H. & Zurier, R.B. (2007) Suppression of fibroblast metalloproteinases by ajulemic acid, a nonpsychoactive cannabinoid acid. J. Cell. Biochem., 100, 184-190.
75. Johnson, J.R., Lossignol, D., Burnell-Nugent, M. & Fallon, M.T. (2012) An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. J. Pain Symptom Manag., 46, 207-218.
76. Julien, B., Grenard, P., Teixeira-Clerc, F., Van Nhieu, J.T., Li, L., Karsak, M., Zimmer, A., Mallat, A. & Lotersztajn, S. (2005) Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology, 128, 742-755.
77. Kano, M., Ohno-Shosaku, T., Hashimotodani, Y., Uchigashima, M. & Watanabe, M. (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol. Rev., 89, 309-380.
78. Karsdal, M.A., Sondergaard, B.C., Arnold, M. & Christiansen, C. (2007) Calcitonin affects both bone and cartilage: a dual action treatment for osteoarthritis? Ann. NY Acad. Sci., 1117, 181-195.
79. Karsdal, M.A., Byrjalsen, I., Henriksen, K., Riis, B.J., Lau, E.M., Arnold, M. & Christiansen, C. (2010) The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study. Osteoarthr. Cartilage, 18, 150-159.
80. Khasabova, I.A., Khasabov, S.G., Harding-Rose, C., Coicou, L.G., Seybold, B.A. & Lindberg, A.E. (2008) A decrease in anandamide signaling contributes to the maintenance of cutaneous mechanical hyperalgesia in a model of bone cancer pain. J. Neurosci., 28, 11141-11152.
81. Kim, H.A., Kim, I., Song, Y.W., Kim, D.H., Niu, J., Guermazi, A., Crema, M.D., Hunter, D.J. & Zhang, Y. (2011) The association between meniscal and cruciate ligament damage and knee pain in community residents. Osteoarthr. Cartilage, 19, 1422-1428.
82. Kosek, E. & Ordeberg, G. (2000) Lack of pressure pain modulation by heterotopic noxious conditioning stimulation in patients with painful osteoarthritis before, but not following, surgical pain relief. Pain, 88, 69-78.
83. van der Kraan, P.M., Vitters, E.L., van de Putte, L.B. & van den Berg, W.B. (1989) Development of osteoarthritic lesions in mice by "metabolic" and "mechanical" alterations in the knee joints. Am. J. Pathol., 135, 1001-1014.
84. Krzeski, P., Buckland-Wright, C., Balint, G., Cline, G.A., Stoner, K., Lyon, R., Beary, J., Aronstein, W.S. & Spector, T.D. (2007) Development of musculoskeletal toxicity without clear benefit after administration of PG-116800, a matrix metalloproteinase inhibitor, to patients with knee osteoarthritis: a randomized, 12-month, double-blind, placebo-controlled study. Arthritis Res. Ther., 9, R109.
85. Kulkarni, B., Bentley, D.E., Elliott, R., Julyan, P.J., Boger, E., Watson, A., Boyle, Y., El-Deredy, W. & Jones, A.K. (2007) Arthritic pain is processed in brain areas concerned with emotions and fear. Arthritis Rheum., 56, 1345-1354.
86. Kwan Tat, S., Lajeunesse, D., Pelletier, J.P. & Martel-Pelletier, J. (2010) Targeting subchondral bone for treating osteoarthritis: what is the evidence? Best Pract. Res. Cl. Rh., 24, 51-70.
87. Kyostio-Moore, S., Nambiar, B., Hutto, E., Ewing, P.J., Piraino, S., Berthelette, P., Sookdeo, C., Matthews, G. & Armentano, D. (2011) STR/ort mice, a model for spontaneous osteoarthritis, exhibit elevated levels of both local and systemic inflammatory markers. Comp. Med., 61, 346-355.
88. La Porta, C., Bura, S.A., Aracil-Fernandez, A., Manzanares, J. & Maldonado, R. (2013) Role of CB1 and CB2 cannabinoid receptors in the development of joint pain induced by monosodium iodoacetate. Pain, 154, 160-174.
89. van Laar, M., Pergolizzi, J.V. Jr., Mellinghoff, H.U., Merchante, I.M., Nalamachu, S., O'Brien, J., Perrot, S. & Raffa, R.B. (2012) Pain treatment in arthritis-related pain: beyond NSAIDs. Open Rheumatol. J., 6, 320-330.
90. Lampropoulou-Adamidou, K., Lelovas, P., Karadimas, E.V., Liakou, C., Triantafillopoulos, I.K., Dontas, I. & Papaioannou, N.A. (2013) Useful animal models for the research of osteoarthritis. Eur. J. Orthop. Surg. Tr., doi: 10.1007/s00590-013-1205-2. [Epub ahead of print].
91. Lane, N.E., Gore, L.R., Cummings, S.R., Hochberg, M.C., Scott, J.C., Williams, E.N. & Nevitt, M.C. (1999) Serum vitamin D levels and incident changes of radiographic hip osteoarthritis: a longitudinal study. Study of Osteoporotic Fractures Research Group. Arthritis Rheum., 42, 854-860.
92. Lee, C., Straus, W.L., Balshaw, R., Barlas, S., Vogel, S. & Schnitzer, T.J. (2004) A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta-analysis. Arthritis Rheum., 51, 746-754.
93. Lee, H.R., Park, K.M., Joung, Y.K., Park, K.D. & Do, S.H. (2012) Platelet-rich plasma loaded hydrogel scaffold enhances chondrogenic differentiation and maturation with up-regulation of CB1 and CB2. J. Control. Release, 159, 332-337.
94. van Lent, P.L., Blom, A.B., Schelbergen, R.F., Sloetjes, A., Lafeber, F.P., Lems, W.F., Cats, H., Vogl, T., Roth, J. & van den Berg, W.B. (2012) Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis. Arthritis Rheum., 64, 1466-1476.
95. Li, G.L., Winter, H., Arends, R., Jay, G.W., Le, V., Young, T. & Huggins, J.P. (2012) Assessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects. Brit. J. Clin. Pharmaco., 73, 706-716.
96. Lim, G., Sung, B., Ji, R.R. & Mao, J. (2003) Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55, 212-2 on neuropathic pain behaviors in rats. Pain, 105, 275-283.
97. Little, C.B. & Zaki, S. (2012) What constitutes an "animal model of osteoarthritis"-the need for consensus? Osteoarthr. Cartilage, 20, 261-267.
98. Liu, J., Li, H., Burstein, S.H., Zurier, R.B. & Chen, J.D. (2003) Activation and binding of peroxisome proliferator-activated receptor gamma by synthetic cannabinoid ajulemic acid. Mol. Pharmacol., 63, 983-992.
99. Longo, U.G., Loppini, M., Fumo, C., Rizzello, G., Khan, W.S., Maffulli, N. & Denaro, V. (2012) Osteoarthritis: new insights in animal models. Open Orthop. J., 6, 558-563.
100. Lories, R.J. & Luyten, F.P. (2011) The bone-cartilage unit in osteoarthritis. Nat. Rev. Rheumatol., 7, 43-49.
101. Lowin, T., Zhu, W., Dettmer-Wilde, K. & Straub, R.H. (2012) Cortisol-mediated adhesion of synovial fibroblasts is dependent on the degradation of anandamide and activation of the endocannabinoid system. Arthritis Rheum., 64, 3867-3876.
102. Lozano-Ondoua, A.N., Wright, C., Vardanyan, A., King, T., Largent-Milnes, T.M. & Nelson, M. (2010) A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss. Life Sci., 86, 646-653.
103. Lunn, C.A., Fine, J., Rojas-Triana, A., Jackson, J.V., Lavey, B., Koz-lowski, J.A., Hipkin, R.W., Lundell, D.J. & Bober, L. (2007) Cannabinoid CB(2)-selective inverse agonist protects against antigen-induced bone loss. Immunopharm. Immunot., 29, 387-401.
104. Lynch, M.E. & Campbell, F. (2011) Cannabinoids for treatment of chronic non-cancer pain: a systematic review of randomized trials. Brit. J. Clin. Pharmaco., 72, 735-744.
105. Majumdar, M.K., Askew, R., Schelling, S., Stedman, N., Blanchet, T., Hopkins, B., Morris, E.A. & Glasson, S.S. (2007) Double-knockout of ADAMTS-4 and ADAMTS-5 in mice results in physiologically normal animals and prevents the progression of osteoarthritis. Arthritis Rheum., 56, 3670-3674.
106. Maldonado, R. & Valverde, O. (2003) Participation of the opioid system in cannabinoid induced antinociception and emotional-like responses. Eur. Neuropsychopharm., 13, 401-410.
107. Maldonado, R., Berrendero, F., Ozaita, A. & Robledo, P. (2011) Neurochemical basis of cannabis addiction. Neuroscience, 5, 1-17.
108. Malfait, A.M., Gallily, R., Sumariwalla, P.F., Malik, A.S., Andreakos, E., Mechoulam, R. & Feldmann, M. (2000) The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collageninduced arthritis. Proc. Natl. Acad. Sci. USA, 97, 9561-9566.
109. Manning, B.H., Martin, W.J. & Meng, I.D. (2003) The rodent amygdala contributes to the production of cannabinoid-induced antinociception. Neuroscience, 120, 1157-1170.
110. Martel-Pelletier, J., Pelletier, J.P. & Fahmi, H. (2003) Cyclooxygenase-2 and prostaglandins in articular tissues. Sem. Arthritis Rheum., 33, 155-167.
111. Martin, W.J., Tsou, K. & Walker, J.M. (1998) Cannabinoid receptor-mediated inhibition of the rat tail-flick reflex after microinjection into the rostral ventromedial medulla. Neurosci. Lett., 242, 33-36.
112. Martin, W.J., Coffin, P.O., Attias, E., Balinsky, M., Tsou, K. & Walker, J.M. (1999) Anatomical basis for cannabinoid-induced antinociception as revealed by intracerebral microinjections. Brain Res., 822, 237-242.
113. Martin-Sanchez, E., Furukawa, T.A., Taylor, J. & Martin, J.L. (2009) Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med., 10, 1353-1368.
114. Mbvundula, E.C., Bunning, R.A. & Rainsford, K.D. (2005) Effects of cannabinoids on nitric oxide production by chondrocytes and proteoglycan degradation in cartilage. Biochem. Pharmacol., 69, 635-640.
115. Mbvundula, E.C., Bunning, R.A. & Rainsford, K.D. (2006) Arthritis and cannabinoids: HU-210 and Win-55, 212-2 prevent IL-1alpha-induced matrix degradation in bovine articular chondrocytes in-vitro. J. Pharm. Pharmacol., 58, 351-358.
116. McAlindon, T., LaValley, M., Schneider, E., Nuite, M., Lee, J.Y., Price, L.L., Lo, G. & Dawson-Hughes, B. (2013) Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial. JAMA, 309, 155-162.
117. McDougall, J.J., Bray, R.C. & Sharkey, K.A. (1997) Morphological and immunohistochemical examination of nerves in normal and injured collateral ligaments of rat, rabbit, and human knee joints. Anat. Rec., 248, 29-39.
118. McDougall, J.J., Yu, V. & Thomson, J. (2008) In vivo effects of CB2 receptor-selective cannabinoids on the vasculature of normal and arthritic rat knee joints. Brit. J. Pharmacol., 153, 358-366.
119. Mease, P.J., Hanna, S., Frakes, E.P. & Altman, R.D. (2011) Pain mechanisms in osteoarthritis: understanding the role of central pain and current approaches to its treatment. J. Rheumatol., 38, 1546-1551.
120. Mechoulam, R. & Parker, L.A. (2013) The endocannabinoid system and the brain. Annu. Rev. Psychol., 64, 21-47.
121. Mechoulam, R., Ben-Shabat, S., Hanus, L., Ligumsky, M., Kaminski, N.E., Schatz, A.R., Gopher, A., Almog, S., Martin, B.R. & Compton, D.R. (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol., 50, 83-90.
122. Meng, I.D., Manning, B.H., Martin, W.J. & Fields, H.L. (1998) An analgesia circuit activated by cannabinoids. Nature, 395, 381-383.
123. Micca, J.L., Ruff, D., Ahl, J. & Wohlreich, M.M. (2013) Safety and efficacy of duloxetine treatment in older and younger patients with osteoarthritis knee pain: a post hoc, subgroup analysis of two randomized, placebo-controlled trials. BMC Musculoskel. Dis., 14, 137.
124. Millns, P.J., Chapman, V. & Kendall, D.A. (2001) Cannabinoid inhibition of the capsaicin-induced calcium response in rat dorsal root ganglion neurones. Brit. J. Pharmacol., 132, 969-971.
125. Miyauchi, S., Machida, A., Onaya, J., Sakamoto, T., Tokuyasu, K. & Iwata, H. (1993) Alterations of proteoglycan synthesis in rabbit articular cartilage induced by intra-articular injection of papain. Osteoarthr. Cartilage, 1, 253-262.
126. Moore, E.E., Bendele, A.M., Thompson, D.L., Littau, A., Waggie, K.S., Reardon, B. & Ellsworth, J.L. (2005) Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthr. Cartilage, 13, 623-631.
127. Moore, R., Straube, S., Wiffen, P., Derry, S. & McQuay, H. (2009) Pregabalin for acute and chronic pain in adults. Cochrane Db. Syst. Rev., 8, CD007076.
128. Morgen, M., Tung, D., Boras, B., Miller, W., Malfait, A.M. & Tortorella, M. (2013) Nanoparticles for improved local retention after intra-articular injection into the knee joint. Pharm. Res., 30, 257-268.
129. Morko, J., Kiviranta, R., Joronen, K., Saamanen, A.M., Vuorio, E. & Salminen-Mankonen, H. (2005) Spontaneous development of synovitis and cartilage degeneration in transgenic mice overexpressing cathepsin K. Arthritis Rheum., 52, 3713-3717.
130. Moskowitz, R.W., Altman, R.D., Hochberg, M.C., Buckwalter, J.A. & Goldberg, V.M. (2007) Osteorhitis, 4th Edn. Lippincott Williams & Wilkins, Philadelphia, pp. 114.
131. Munro, S., Thomas, K.L. & Abu-Shaar, M. (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature, 365, 61-65.
132. Nagai, T., Kyo, A., Hasui, K., Takao, S. & Matsuyama, T. (2012) Efficacy of an immunotoxin to folate receptor beta in the intra-articular treatment of antigen-induced arthritis. Arthritis Res. Ther., 14, R106.
133. Neuhold, L.A., Killar, L., Zhao, W., Sung, M.L., Warner, L., Kulik, J., Turner, J., Wu, W., Billinghurst, C., Meijers, T., Poole, A.R., Babij, P. & DeGennaro, L.J. (2001) Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice. J. Clin. Invest., 107, 35-44.
134. Ofek, O., Karsak, M., Leclerc, N., Fogel, M., Frenkel, B., Wright, K., Tam, J., Attar-Namdar, M., Kram, V., Shohami, E., Mechoulam, R., Zimmer, A. & Bab, I. (2006) Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc. Natl. Acad. Sci. USA, 103, 696-701.
135. Orita, S., Ishikawa, T., Miyagi, M., Ochiai, N., Inoue, G., Eguchi, Y., Kamoda, H., Arai, G., Toyone, T., Aoki, Y., Kubo, T., Takahashi, K. & Ohtori, S. (2011) Pain-related sensory innervation in monoiodoacetate-induced osteoarthritis in rat knees that gradually develops neuronal injury in addition to inflammatory pain. BMC Musculoskel. Dis., 12, 134.
136. van Osch, G.J., van der Kraan, P.M. & van den Berg, W.B. (1994) Site-specific cartilage changes in murine degenerative knee joint disease induced by iodoacetate and collagenase. J. Orthop. Res., 12, 168-175.
137. Osei-Hyiaman, D., Harvey-White, J., Batkai, S. & Kunos, G. (2006) The role of the endocannabinoid system in the control of energy homeostasis. Int. J. Obesity, 30(Suppl 1), S33-S38.
138. Pelletier, J.P., DiBattista, J.A., Raynauld, J.P., Wilhelm, S. & Martel-Pelletier, J. (1995) The in vivo effects of intraarticular corticosteroid injections on cartilage lesions, stromelysin, interleukin-1, and oncogene protein synthesis in experimental osteoarthritis. Lab. Invest., 72, 578-586.
139. Pelletier, J.P., Jovanovic, D.V., Lascau-Coman, V., Fernandes, J.C., Manning, P.T., Connor, J.R., Currie, M.G. & Martel-Pelletier, J. (2000) Selective inhibition of inducible nitric oxide synthase reduces progression of experimental osteoarthritis in vivo: possible link with the reduction in chondrocyte apoptosis and caspase 3 level. Arthritis Rheum., 43, 1290-1299.
140. Pelletier, J.P., Mineau, F., Boileau, C. & Martel-Pelletier, J. (2003) Diacerein reduces the level of cartilage chondrocyte DNA fragmentation and death in experimental dog osteoarthritic cartilage at the same time that it inhibits caspase-3 and inducible nitric oxide synthase. Clin. Exp. Rheumatol., 21, 71-77.
141. Pertwee, R.G. (2009) Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Brit. J. Pharmacol., 156, 397-411.
142. Pertwee, R.G. (2012) Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities. Philos. T. Roy. Soc. B., 367, 3353-3363.
143. Pertwee, R.G., Howlett, A.C., Abood, M.E., Alexander, S.P., Di Marzo, V., Elphick, M.R., Greasley, P.J., Hansen, H.S., Kunos, G., Mackie, K., Mechoulam, R. & Ross, R.A. (2010) Cannabinoid receptors and their ligands: beyond CB(1) and CB(2). Pharmacol. Rev., 62, 588-631.
144. Pham, T., Le Henanff, A., Ravaud, P., Dieppe, P., Paolozzi, L. & Dougados, M. (2004) Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis. Ann. Rheum. Dis., 63, 1611-1617.
145. Pulsatelli, L., Addimanda, O., Brusi, V., Pavloska, B. & Meliconi, R. (2013) New findings in osteoarthritis pathogenesis: therapeutic implications. Ther. Adv. Chronic Dis., 4, 23-43.
146. Racz, I., Nadal, X., Alferink, J., Banos, J.E., Rehnelt, J., Martin, M., Pintado, B., Gutierrez-Adan, A., Sanguino, E., Manzanares, J., Zimmer, A. & Maldonado, R. (2008) Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain. J. Neurosci., 28, 12125-12135.
147. Rahman, W., Bauer, C., Bannister, K., Vonsy, J., Dolphin, A. & Dickenson, A. (2009) Descending serotonergic facilitation and the antinociceptive effects of pregabalin in a rat model of osteoarthritic pain. Mol. Pain, 7, 45.
148. Ravaud, P., Moulinier, L., Giraudeau, B., Ayral, X., Guerin, C., Noel, E., Thomas, P., Fautrel, B., Mazieres, B. & Dougados, M. (1999) Effects of joint lavage and steroid injection in patients with osteoarthritis of the knee: results of a multicenter, randomized, controlled trial. Arthritis Rheum., 42, 475-482.
149. Raynauld, J.P., Buckland-Wright, C., Ward, R., Choquette, D., Haraoui, B., Martel-Pelletier, J., Uthman, I., Khy, V., Tremblay, J.L., Bertrand, C. & Pelletier, J.P. (2003) Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum., 48, 370-377.
150. Raynauld, J.P., Martel-Pelletier, J., Bias, P., Laufer, S., Haraoui, B., Choquette, D., Beaulieu, A.D., Abram, F., Dorais, M., Vignon, E. & Pelletier, J.P. (2009) Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI. Ann. Rheum. Dis., 68, 938-947.
151. Rea, K., Roche, M. & Finn, D.P. (2007) Supraspinal modulation of pain by cannabinoids: the role of GABA and glutamate. Brit. J. Pharmacol., 152, 633-648.
152. Richardson, D., Pearson, R.G., Kurian, N., Latif, M.L., Garle, M.J., Barrett, D.A., Kendall, D.A., Scammell, B.E., Reeve, A.J. & Chapman, V. (2008) Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res. Ther., 10, R43.
153. Richy, F., Bruyere, O., Ethgen, O., Cucherat, M., Henrotin, Y. & Reginster, J.Y. (2003) Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch. Intern. Med., 163, 1514-1522.
154. Rieder, S.A., Chauhan, A., Singh, U., Nagarkatti, M. & Nagarkatti, P. (2010) Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression. Immunobiology, 215, 598-605.
155. Rodríguez De Fonseca, F., Gorriti, M.A., Bilbao, A., Escuredo, L., García-Segura, L.M., Piomelli, D. & Navarro, M. (2001) Role of the endogenous cannabinoid system as a modulator of dopamine transmission: implications for Parkinson's disease and schizophrenia. Neurotox. Res., 3, 23-35.
156. Rodriguez, M.J., Robledo, P., Andrade, C. & Mahy, N. (2005) In vivo co-ordinated interactions between inhibitory systems to control glutamatemediated hippocampal excitability. J. Neurochem., 95, 651-661.
157. Roques, B.P., Fournié-Zaluski, M.C. & Wurm, M. (2012) Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain. Nat. Rev. Drug Discov., 11, 292-310.
158. Rudolphi, K., Gerwin, N., Verzijl, N., van der Kraan, P. & van den Berg, W. (2003) Pralnacasan, an inhibitor of interleukin-1beta converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthr. Cartilage, 11, 738-746.
159. Saamanen, A.K., Salminen, H.J., Dean, P.B., De Crombrugghe, B., Vuorio, E.I. & Metsaranta, M.P. (2000) Osteoarthritis-like lesions in transgenic mice harboring a small deletion mutation in type II collagen gene. Osteoarthr. Cartilage, 8, 248-257.
160. Sagar, D.R., Staniaszek, L.E., Okine, B.N., Woodhams, S., Norris, L.M., Pearson, R.G., Garle, M.J., Alexander, S.P., Bennett, A.J., Barrett, D.A., Kendall, D.A., Scammell, B.E. & Chapman, V. (2010) Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain. Arthritis Rheum., 62, 3666-3676.
161. Salo, P.T., Theriault, E. & Wiley, R.G. (1997) Selective ablation of rat knee joint innervation with injected immunotoxin: a potential new model for the study of neuropathic arthritis. J. Orthop. Res., 15, 622-628.
162. Sanchez, C., Rueda, D., Segui, B., Galve-Roperh, I., Levade, T. & Guzman, M. (2001) The CB(1) cannabinoid receptor of astrocytes is coupled to sphingomyelin hydrolysis through the adaptor protein fan. Mol. Pharmacol., 59, 955-959.
163. Sarzi-Puttini, P., Cimmino, M.A., Scarpa, R., Caporali, R., Parazzini, F., Zaninelli, A., Atzeni, F. & Canesi, B. (2005) Osteoarthritis: an overview of the disease and its treatment strategies. Semin. Arthritis Rheu., 35, 1-10.
164. Schaible, H.G., Richter, F., Ebersberger, A., Boettger, M.K., Vanegas, H., Natura, G., Vazquez, E. & Segond von Banchet, G. (2009) Joint pain. Exp. Brain Res., 196, 153-162.
165. Schuelert, N. & McDougall, J.J. (2008) Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. Arthritis Rheum., 58, 145-153.
166. Schuelert, N., Zhang, C., Mogg, A.J., Broad, L.M., Hepburn, D.L., Nisenbaum, E.S., Johnson, M.P. & McDougall, J.J. (2010) Paradoxical effects of the cannabinoid CB2 receptor agonist GW405833 on rat osteoarthritic knee joint pain. Osteoarthr. Cartilage, 18, 1536-1543.
167. Schuelert, N., Johnson, M.P., Oskins, J.L., Jassal, K., Chambers, M.G. & McDougall, J.J. (2011) Local application of the endocannabinoid hydrolysis inhibitor URB597 reduces nociception in spontaneous and chemically induced models of osteoarthritis. Pain, 152, 975-981.
168. Selvi, E., Lorenzini, S., Garcia-Gonzalez, E., Maggio, R., Lazzerini, P.E., Capecchi, P.L., Balistreri, E., Spreafico, A., Niccolini, S., Pompella, G., Natale, M.R., Guideri, F., Laghi Pasini, F., Galeazzi, M. & Marcolongo, R. (2008) Inhibitory effect of synthetic cannabinoids on cytokine production in rheumatoid fibroblast-like synoviocytes. Clin. Exp. Rheumatol., 26, 574-581.
169. Sendzik, J., Lode, H. & Stahlmann, R. (2009) Quinolone-induced arthropathy: an update focusing on new mechanistic and clinical data. Int. J. Antimicrob. Ag., 33, 194-200.
170. Shin, K., Kim, J.W., Moon, K.W., Yang, J.A., Lee, E.Y., Song, Y.W. & Lee, E.B. (2013) The efficacy of diacerein in hand osteoarthritis: a double-blind, randomized, placebo-controlled study. Clin. Ther., 35, 431-439.
171. van Sickle, M.D., Duncan, M., Kingsley, P.J., Mouihate, A., Urbani, P., Mackie, K., Stella, N., Makriyannis, A., Piomelli, D., Davison, J.S., Marnett, L.J., Di Marzo, V., Pittman, Q.J., Patel, K.D. & Sharkey, K.A. (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science, 310, 329-332.
172. Sniekers, Y.H., Weinans, H., Bierma-Zeinstra, S.M., van Leeuwen, J.P. & van Osch, G.J. (2008) Animal models for osteoarthritis: the effect of ovariectomy and estrogen treatment - a systematic approach. Osteoarthr. Cartilage, 16, 533-541.
173. Sofat, N., Ejindu, V. & Kiely, P. (2011) What makes osteoarthritis painful? The evidence for local and central pain processing. Rheumatology (Oxford), 50, 2157-2165.
174. Sowers, M.R., McConnell, D., Jannausch, M., Buyuktur, A.G., Hochberg, M. & Jamadar, D.A. (2006) Estradiol and its metabolites and their association with knee osteoarthritis. Arthritis Rheum., 54, 2481-2487.
175. Spector, T.D., Conaghan, P.G., Buckland-Wright, J.C., Garnero, P., Cline, G.A., Beary, J.F., Valent, D.J. & Meyer, J.M. (2005) Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]. Arthritis Res. Ther., 7, R625-R633.
176. van der Staay, F.J., Arndt, S.S. & Nordquist, R.E. (2009) Evaluation of animal models of neurobehavioral disorders. Behav. Brain Funct., 25, 5-11.
177. Ständer, S., Schmelz, M., Metze, D., Luger, T. & Rukwied, R. (2005) Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J. Dermatol. Sci., 38, 177-188.
178. Sumariwalla, P.F., Gallily, R., Tchilibon, S., Fride, E., Mechoulam, R. & Feldmann, M. (2004) A novel synthetic, nonpsychoactive cannabinoid acid (HU-320) with anti-inflammatory properties in murine collagen-induced arthritis. Arthritis Rheum., 50, 985-998.
179. Tsou, K., Brown, S., Sanudo-Pena, M.C., Mackie, K. & Walker, J.M. (1998) Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience, 83, 393-411.
180. Vincent, T.L., Williams, R.O., Maciewicz, R., Silman, A. & Garside, P. (2012) Mapping pathogenesis of arthritis through small animal models. Rheumatology (Oxford), 51, 1931-1941.
181. Waldman, S.D. (2009) Pain Review. Saunders Elsevier, Philadelphia, USA.
182. Walter, L., Franklin, A., Witting, A., Wade, C., Xie, Y., Kunos, G., Mackie, K. & Stella, N. (2003) Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J. Neurosci., 23, 1398-1405.
183. Wang, T., Collet, J.P., Shapiro, S. & Ware, M.A. (2008) Adverse effects of medical cannabinoids: a systematic review. CMAJ, 178, 1669-1678.
184. Westlake, T.M., Howlett, A.C., Bonner, T.I., Matsuda, L.A. & Herkenham, M. (1994) Cannabinoid receptor binding and messenger RNA expression in human brain: an in vitro receptor autoradiography and in situ hybridization histochemistry study of normal aged and Alzheimer's brains. Neuroscience, 63, 637-652.
185. Whyte, L.S., Ford, L., Ridge, S.A., Cameron, G.A., Rogers, M.J. & Ross, R.A. (2012) Cannabinoids and bone: endocannabinoids modulate human osteoclast function in vitro. Brit. J. Pharmacol., 165, 2584-2597.
186. Wieland, H.A., Michaelis, M., Kirschbaum, B.J. & Rudolphi, K.A. (2005) Osteoarthritis - an untreatable disease? Nat. Rev. Drug Discov., 4, 331-344.
187. Wilson, R.I. & Nicoll, R.A. (2002) Endocannabinoid signaling in the brain. Science, 296, 678-682.
188. Yao, B.B., Hsieh, G.C., Frost, J.M., Fan, Y., Garrison, T.R., Daza, A.V., Grayson, G.K., Zhu, C.Z., Pai, M., Chandran, P., Salyers, A.K., Wensink, E.J., Honore, P., Sullivan, J.P., Dart, M.J. & Meyer, M.D. (2008) In vitro and in vivo characterization of A-796260: a selective cannabinoid CB2 receptor agonist exhibiting analgesic activity in rodent pain models. Brit. J. Pharmacol., 153, 390-401.
189. Yasuda, Y., Kaleta, J. & Bromme, D. (2005) The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics. Adv. Drug Deliver. Rev., 57, 973-993.
190. Yu, L.P. Jr., Smith, G.N. Jr., Brandt, K.D., Myers, S.L., O'Connor, B.L. & Brandt, D.A. (1992) Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline. Arthritis Rheum., 35, 1150-1159.
191. 2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models. Eur. J. Neurosci., 17, 2750-2754.
192. Zhang, W., Moskowitz, R.W., Nuki, G., Abramson, S., Altman, R.D., Arden, N., Bierma-Zeinstra, S., Brandt, K.D., Croft, P., Doherty, M., Dougados, M., Hochberg, M., Hunter, D.J., Kwoh, K., Lohmander, L.S. & Tugwell, P. (2008) OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr. Cartilage, 16, 137-162.
193. Zurier, R.B., Rossetti, R.G., Lane, J.H., Goldberg, J.M., Hunter, S.A. & Burstein, S.H. (1998) Dimethylheptyl-THC-11 oic acid: a nonpsychoactive antiinflammatory agent with a cannabinoid template structure. Arthritis Rheum., 41, 163-170.
194. Zurier, R.B., Rossetti, R.G., Burstein, S.H. & Bidinger, B. (2003) Suppression of human monocyte interleukin-1beta production by ajulemic acid, a nonpsychoactive cannabinoid. Biochem. Pharmacol., 65, 649-655.