Endocannabinoids and neuropathic pain: Focus on neuron-glia and endocannabinoid-neurotrophin interactions

European Journal of Neuroscience

Volumn 39, Issue 3, 2014, Pages 401-408

  Luongo, Livio ^a   Maione, Sabatino ^a   Di Marzo, Vincenzo ^b  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

^b CNR   (Italy)

Author keywords

Endocannabinoids; Glial cells; Neurotrophins; Vanilloid receptor 1

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; CITALOPRAM; ENDOCANNABINOID; FLUPHENAZINE; G PROTEIN COUPLED RECEPTOR; ISOCARBOXAZID; NERVE GROWTH FACTOR; NEUROTROPHIN; NORTRIPTYLINE; RISPERIDONE; TRANSIENT RECEPTOR POTENTIAL CHANNEL M8; VANILLOID RECEPTOR 1;

ARTICLE; GLIA; HUMAN; HYPERALGESIA; MACROGLIA; MICROGLIA; MOLECULAR INTERACTION; NEUROPATHIC PAIN; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; SPINAL CORD DORSAL HORN; SPINAL GANGLION; UPREGULATION;

ENDOCANNABINOIDS; GLIAL CELLS; NEUROTROPHINS; VANILLOID RECEPTOR-1;

ANIMALS; ENDOCANNABINOIDS; HUMANS; NERVE GROWTH FACTORS; NEURALGIA; NEUROGLIA; NEURONS;

EID: 84893390483     PISSN: 0953816X     EISSN: 14609568     Source Type: Journal    
DOI: 10.1111/ejn.12440     Document Type: Article

References (94)

1. Aguado, T., Romero, E., Monory, K., Palazuelos, J., Sendtner, M., Marsicano, G., Lutz, B., Guzmán, M. & Galve-Roperh, I. (2007) The CB1 cannabinoid receptor mediates excitotoxicity-induced neural progenitor proliferation and neurogenesis. J. Biol. Chem., 282, 23892-23898.
2. Anand, U., Otto, W.R., Casula, M.A., Day, N.C., Davis, J.B., Bountra, C., Birch, R. & Anand, P. (2006) The effect of neurotrophic factors on morphology, TRPV1 expression and capsaicin responses of cultured human DRG sensory neurons. Neurosci. Lett., 399, 51-56.
3. Anand, P., Whiteside, G., Fowler, C.J. & Hohmann, A.G. (2009) Targeting CB2 receptors and the endocannabinoid system for the treatment of pain. Brain Res. Rev., 60, 255-266. 2008. Review.
4. Arevalo-Martin, A., Garcia-Ovejero, D., Sierra-Palomares, Y., Paniagua-Torija, B., Gonzalez-Gil, I., Ortega-Gutierrez, S. & Molina-Holgado, E. (2012) Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery. PLoS ONE, 7, e49057.
5. Arévalo-Martín, A., Vela, J.M., Molina-Holgado, E., Borrell, J. & Guaza, C. (2003) Therapeutic action of cannabinoids in a murine model of multiple sclerosis. J. Neurosci., 23, 2511-2516.
6. Aso, E., Ozaita, A., Valdizán, E.M., Ledent, C., Pazos, A., Maldonado, R. & Valverde, O. (2008) BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice. J. Neurochem., 105, 565-572.
7. Barbara, G., Alloui, A., Nargeot, J., Lory, P., Eschalier, A., Bourinet, E. & Chemin, J. (2009) T-type calcium channel inhibition underlies the analgesic effects of the endogenous lipoamino acids. J. Neurosci., 29, 13106-13114.
8. Bayatti, N., Hermann, H., Lutz, B. & Behl, C. (2005) Corticotropin-releasing hormone-mediated induction of intracellular signaling pathways and brain-derived neurotrophic factor expression is inhibited by the activation of the endocannabinoid system. Endocrinology, 146, 1205-1213.
9. Beltramo, M., Bernardini, N., Bertorelli, R., Campanella, M., Nicolussi, E., Fredduzzi, S. & Reggiani, A. (2006) CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms. Eur. J. Neurosci., 23, 1530-1538.
10. Berghuis, P., Dobszay, M.B., Wang, X., Spano, S., Ledda, F., Sousa, K.M., Schulte, G., Ernfors, P., Mackie, K., Paratcha, G., Hurd, Y.L. & Harkany, T. (2005) Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor. Proc. Natl. Acad. Sci. USA, 102, 19115-19120.
11. Bisogno, T. & Di Marzo, V. (2010) Cannabinoid receptors and endocannabinoids: role in neuroinflammatory and neurodegenerative disorders. CNS Neurol. Disord.-Dr., 9, 564-573. Review.
12. Bonica, J.J. (1970) Pain-basic principles of management. Northwest Med., 69, 567-568.
13. Calignano, A., La Rana, G., Giuffrida, A. & Piomelli, D. (1998) Control of pain initiation by endogenous cannabinoids. Nature, 394, 277-281.
14. Cantarella, G., Scollo, M., Lempereur, L., Saccani-Jotti, G., Basile, F. & Bernardini, R. (2011) Endocannabinoids inhibit release of nerve growth factor by inflammation-activated mast cells. Biochem. Pharmacol., 82, 380-388.
15. Carrier, E.J., Kearn, C.S., Barkmeier, A.J., Breese, N.M., Yang, W., Nithipatikom, K., Pfister, S.L., Campbell, W.B. & Hillard, C.J. (2004) Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism. Mol. Pharmacol., 65, 999-1007.
16. Clark, A.K., Wodarski, R., Guida, F., Sasso, O. & Malcangio, M. (2010) Cathepsin S release from primary cultured microglia is regulated by the P2X7 receptor. Glia, 58, 1710-1726.
17. Clayton, N., Marshall, F.H., Bountra, C. & O'Shaughnessy, C.T. (2002) CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain. Pain, 96, 253-260.
18. Costa, B., Trovato, A.E., Colleoni, M., Giagnoni, G., Zarini, E. & Croci, T. (2005) Effect of the cannabinoid CB1 receptor antagonist, SR141716, on nociceptive response and nerve demyelination in rodents with chronic constriction injury of the sciatic nerve. Pain, 116, 52-61.
19. Costa, B., Comelli, F., Bettoni, I., Colleoni, M. & Giagnoni, G. (2008) The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors. Pain, 139, 541-550.
20. Coull, J.A., Beggs, S., Boudreau, D., Boivin, D., Tsuda, M., Inoue, K., Gravel, C., Salter, M.W. & De Koninck, Y. (2005) BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature, 438, 1017-1021.
21. Cravatt, B.F. & Lichtman, A.H. (2004) The endogenous cannabinoid system and its role in nociceptive behavior. J. Neurobiol., 61, 149-160. Review.
22. De Chiara, V., Angelucci, F., Rossi, S., Musella, A., Cavasinni, F., Cantarella, C., Mataluni, G., Sacchetti, L., Napolitano, F., Castelli, M., Caltagirone, C., Bernardi, G., Maccarrone, M., Usiello, A. & Centonze, D. (2010) Brain-derived neurotrophic factor controls cannabinoid CB1 receptor function in the striatum. J. Neurosci., 30, 8127-8137.
23. De Petrocellis, L., Starowicz, K., Moriello, A.S., Vivese, M., Orlando, P. & Di Marzo, V. (2007) Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): effect of cAMP, cannabinoid CB(1) receptors and endovanilloids. Exp. Cell Res., 313, 1911-1920.
24. Di Marzo, V. (1998) Endocannabinoids and other fatty acid derivates with cannabimimetic properties: biochemistry and possible physiopathological relevance. Biochim. Biophys. Acta, 1392, 153-175.
25. Di Marzo, V., Melck, D., Orlando, P., Bisogno, T., Zagoory, O., Bifulco, M., Vogel, Z. & De Petrocellis, L. (2001) Palmitoylethanolamide inhibits the expression of fatty acid amide hydrolase and enhances the anti-proliferative effect of anandamide in human breast cancer cells. Biochem. J., 358, 249-255.
26. Dinh, T.P., Freund, T.F. & Piomelli, D. (2002) A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation. Chem. Phys. Lipids, 12, 149-158. Review.
27. Dixon, W.E. (1899) The pharmacology of cannabis indica. Brit. Med. J., 2, 1354-1357.
28. 9-tetrahydrocannabinol and rimonabant in the olfactory bulbectomised rat model of depression. Pharmacol. Biochem. Be., 102, 357-365.
29. Evans, R.M., Scott, R.H. & Ross, R.A. (2007) Chronic exposure of sensory neurones to increased levels of nerve growth factor modulates CB1/TRPV1 receptor crosstalk. Brit. J. Pharmacol., 152, 404-413.
30. Farquhar-Smith, W.P. & Rice, A.S. (2003) A novel neuroimmune mechanism in cannabinoid-mediated attenuation of nerve growth factor-induced hyperalgesia. Anesthesiology, 99, 1391-1401.
31. Farquhar-Smith, W.P., Jaggar, S.I. & Rice, A.S. (2002) Attenuation of nerve growth factor-induced visceral hyperalgesia via cannabinoid CB(1) and CB(2)-like receptors. Pain, 97, 11-21.
32. Fowler, C.J., Jonsson, K.O. & Tiger, G. (2001) Fatty acid amide hydrolase: biochemistry, pharmacology, and therapeutic possibilities for an enzyme hydrolyzing anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleamide. Biochem. Pharmacol., 62, 517-526. Review.
33. Gatta, L., Piscitelli, F., Giordano, C., Boccella, S., Lichtman, A., Maione, S. & Di Marzo, V. (2012) Discovery of prostamide F2α and its role in inflammatory pain and dorsal horn nociceptive neuron hyperexcitability. PLoS ONE, 7, e31111.
34. Giordano, C., Cristino, L., Luongo, L., Siniscalco, D., Petrosino, S., Piscitelli, F., Marabese, I., Gatta, L., Rossi, F., Imperatore, R., Palazzo, E., de Novellis, V., Di Marzo, V. & Maione, S. (2012) TRPV1-dependent and -independent alterations in the limbic cortex of neuropathic mice: impact on glial caspases and pain perception. Cereb. Cortex, 22, 2495-2518.
35. Goya, P., Jagerovic, N., Hernandez-Folgado, L. & Martin, M.I. (2003) Cannabinoids and neuropathic pain. Mini.-Rev. Med. Chem., 3, 765-772. Review.
36. Guasti, L., Richardson, D., Jhaveri, M., Eldeeb, K., Barrett, D., Elphick, M.R., Alexander, S.P., Kendall, D., Michael, G.J. & Chapman, V. (2009) Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain. Mol. Pain., 5, 35.
37. Hassanzadeh, P. & Hassanzadeh, A. (2011) The Role of the Endocannabinoids in Suppression of the Hypothalamic-pituitary-adrenal Axis Activity by Doxepin. Iran J. Basic Med. Sci., 4, 414-421.
38. Hassanzadeh, P. & Rahimpour, S. (2011) The cannabinergic system is implicated in the upregulation of central NGF protein by psychotropic drugs. Psychopharmacology, 215, 129-141.
39. Hermanson, D.J., Hartley, N.D., Gamble-George, J., Brown, N., Shonesy, B.C., Kingsley, P.J., Colbran, R.J., Reese, J., Marnett, L.J. & Patel, S. (2013) Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation. Nat. Neurosci., 16, 1291-1298.
40. Heyman, E., Gamelin, F.X., Goekint, M., Piscitelli, F., Roelands, B., Leclair, E., Di Marzo, V. & Meeusen, R. (2012) Intense exercise increases circulating endocannabinoid and BDNF levels in humans-possible implications for reward and depression. Psychoneuroendocrino., 37, 844-851.
41. Hsu, K.L., Tsuboi, K., Adibekian, A., Pugh, H., Masuda, K. & Cravatt, B.F. (2012) DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses. Nat. Chem. Biol., 8, 999-1007.
42. Ibrahim, M.M., Deng, H., Zvonok, A., Cockayne, D.A., Kwan, J., Mata, H.P., Vanderah, T.W., Lai, J., Porreca, F., Makriyannis, A. & Malan, T.P. Jr (2003) Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS. Proc. Natl. Acad. Sci. USA, 100, 10529-10533.
43. 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.
44. Ikeda, H., Ikegami, M., Kai, M., Ohsawa, M. & Kamei, J. (2013) Activation of spinal cannabinoid CB2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice. Neuroscience, 250, 446-454.
45. Jhaveri, M.D., Sagar, D.R., Elmes, S.J., Kendall, D.A. & Chapman, V. (2007) Cannabinoid CB2 receptor-mediated anti-nociception in models of acute and chronic pain. Mol. Neurobiol., 36, 26-35. Review.
46. Johns, D.G., Behm, D.J., Walker, D.J., Ao, Z., Shapland, E.M., Daniels, D.A., Riddick, M., Dowell, S., Staton, P.C., Green, P., Shabon, U., Bao, W., Aiyar, N., Yue, T.L., Brown, A.J., Morrison, A.D. & Douglas, S.A. (2007) The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Brit. J. Pharmacol., 152, 825-831.
47. Kalant, H. (2004) Adverse effects of cannabis on health: an update of the literature since 1996. Prog. Neuro-Psychoph., 28, 849-863.
48. Keimpema, E., Tortoriello, G., Alpár, A., Capsoni, S., Arisi, I., Calvigioni, D., Hu, S.S., Cattaneo, A., Doherty, P., Mackie, K. & Harkany, T. (2013) Nerve growth factor scales endocannabinoid signaling by regulating monoacylglycerol lipase turnover in developing cholinergic neurons. Proc. Natl. Acad. Sci. USA, 11, 1935-1940.
49. Kinsey, S.G., Long, J.Z., Cravatt, B.F. & Lichtman, A.H. (2010) Fatty acid amide hydrolase and monoacylglycerol lipase inhibitors produce anti-allodynic effects in mice through distinct cannabinoid receptor mechanisms. J. Pain, 11, 1420-1428.
50. Kraft, B., Frickey, N.A., Kaufmann, R.M., Reif, M., Frey, R., Gustorff, B. & Kress, H.G. (2008) Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers. Anesthesiology, 109, 101-110.
51. Kreutz, S., Koch, M., Böttger, C., Ghadban, C., Korf, H.W. & Dehghani, F. (2009) 2-Arachidonoylglycerol elicits neuroprotective effects on excitotoxically lesioned dentate gyrus granule cells via abnormal-cannabidiol-sensitive receptors on microglial cells. Glia, 5, 286-289.
52. Landry, R.P., Martinez, E., DeLeo, J.A. & Romero-Sandoval, E.A. (2012) Spinal cannabinoid receptor type 2 agonist reduces mechanical allodynia and induces mitogen-activated protein kinase phosphatases in a rat model of neuropathic pain. J. Pain, 13, 836-848.
53. Lauckner, J.E., Jensen, J.B., Chen, H.Y., Lu, H.C., Hille, B. & Mackie, K. (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc. Natl. Acad. Sci. USA, 105, 2699-2704.
54. Lemtiri-Chlieh, F. & Levine, E.S. (2010) BDNF evokes release of endogenous cannabinoids at layer 2/3 inhibitory synapses in the neocortex. J. Neurophysiol., 104, 1923-1932.
55. Luongo, L., Palazzo, E., Tambaro, S., Giordano, C., Gatta, L., Scafuro, M.A., Rossi, F.S., Lazzari, P., Pani, L., de Novellis, V., Malcangio, M. & Maione, S. (2010) 1-(2′, 4′-dichlorophenyl)-6-methyl-N-cyclohexylamine-1, 4-dihydroindeno[1, 2-c]pyrazole-3-carboxamide, a novel CB2 agonist, alleviates neuropathic pain through functional microglial changes in mice. Neurobiol. Dis., 37, 177-185.
56. Maione, S., Bisogno, T., de Novellis, V., Palazzo, E., Cristino, L., Valenti, M., Petrosino, S., Guglielmotti, V., Rossi, F. & Di Marzo, V. (2006) Elevation of endocannabinoid levels in the ventrolateral periaqueductal grey through inhibition of fatty acid amide hydrolase affects descending nociceptive pathways via both cannabinoid receptor type 1 and transient receptor potential vanilloid type-1 receptors. J. Pharmacol. Exp. Ther., 316, 969-982.
57. Maione, S., Costa, B. & Di Marzo, V. (2013) Endocannabinoids: a unique opportunity to develop multitarget analgesics. Pain, 154, S87-S93.
58. Maison, P., Walker, D.J., Walsh, F.S., Williams, G. & Doherty, P. (2009) BDNF regulates neuronal sensitivity to endocannabinoids. Neurosci. Lett., 467, 90-94.
59. Maresz, K., Carrier, E.J., Ponomarev, E.D., Hillard, C.J. & Dittel, B.N. (2005) Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J. Neurochem., 95, 437-445.
60. Marrs, W.R., Blankman, J.L., Horne, E.A., Thomazeau, A., Lin, Y.H., Coy, J., Bodor, A.L., Muccioli, G.G., Hu, S.S., Woodruff, G., Fung, S., Lafourcade, M., Alexander, J.P., Long, J.Z., Li, W., Xu, C., Möller, T., Mackie, K., Manzoni, O.J., Cravatt, B.F. & Stella, N. (2010) The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors. Nat. Neurosci., 13, 951-957.
61. Melck, D., Rueda, D., Galve-Roperh, I., De Petrocellis, L., Guzmán, M. & Di Marzo, V. (1999) Involvement of the cAMP/protein kinase A pathway and of mitogen-activated protein kinase in the anti-proliferative effects of anandamide in human breast cancer cells. FEBS Lett., 463, 235-240.
62. Melck, D., De Petrocellis, L., Orlando, P., Bisogno, T., Laezza, C., Bifulco, M. & Di Marzo, V. (2000) Suppression of nerve growth factor Trk receptors and prolactin receptors by endocannabinoids leads to inhibition of human breast and prostate cancer cell proliferation. Endocrinology, 141, 118-126.
63. Merighi, S., Gessi, S., Varani, K., Fazzi, D., Mirandola, P. & Borea, P.A. (2012) Cannabinoid CB(2) receptor attenuates morphine-induced inflammatory responses in activated microglial cells. Brit. J. Pharmacol., 166, 2371-2385.
64. Millan, M.J. (1999) The induction of pain: an integrative review. Prog. Neurobiol., 57, 1-164. Review.
65. Munro, S., Thomas, K.L. & Abu-Shaar, M. (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature, 365, 61-65.
66. de Novellis, V., Vita, D., Gatta, L., Luongo, L., Bellini, G., De Chiaro, M., Marabese, I., Siniscalco, D., Boccella, S., Piscitelli, F., Di Marzo, V., Palazzo, E., Rossi, F. & Maione, S. (2011) The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats. Mol. Pain., 7, 7.
67. Oz, M. (2006) Receptor-independent actions of cannabinoids on cell membranes: focus on endocannabinoids. Pharmacol. Therapeut., 111, 114-144. Review.
68. Palazzo, E., de Novellis, V., Petrosino, S., Marabese, I., Vita, D., Giordano, C., Di Marzo, V., Mangoni, G.S., Rossi, F. & Maione, S. (2006) Neuropathic pain and the endocannabinoid system in the dorsal raphe: pharmacological treatment and interactions with the serotonergic system. Eur. J. Neurosci., 24, 2011-2020.
69. Panikashvilim, D., Simeonidou, C., Ben-Shabat, S., Hanus, L., Breuer, A., Mechoulam, R. & Shohami, E. (2001) An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature, 413, 527-531.
70. Pernía-Andrade, A.J., Kato, A., Witschi, R., Nyilas, R., Katona, I., Freund, T.F., Watanabe, M., Filitz, J., Koppert, W., Schüttler, J., Ji, G., Neugebauer, V., Marsicano, G., Lutz, B., Vanegas, H. & Zeilhofer, H.U. (2009) Spinal endocannabinoids and CB1 receptors mediate C-fiber-induced heterosynaptic pain sensitization. Science, 325, 760-764.
71. Pertwee, R.G. (2001) Cannabinoid receptors and pain. Prog. Neurobiol., 63, 569-611. Review.
72. Petrosino, S. & Di Marzo, V. (2010) FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels. Curr. Opin. Invest. Dr., 11, 51-62. Review.
73. Petrosino, S., Palazzo, E., de Novellis, V., Bisogno, T., Rossi, F., Maione, S. & Di Marzo, V. (2007) Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats. Neuropharmacology, 52, 415-422.
74. Racz, I., Nadal, X., Alferink, J., Baños, J.E., Rehnelt, J., Martín, 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.
75. Rice, A.S., Farquhar-Smith, W.P. & Nagy, I. (2002) Endocannabinoids and pain: spinal and peripheral analgesia in inflammation and neuropathy. Prostaglandins Leukot. Ess., 66, 243-256. Review.
76. Romero-Sandoval, A., Nutile-McMenemy, N. & DeLeo, J.A. (2008) Spinal microglial and perivascular cell cannabinoid receptor type 2 activation reduces behavioral hypersensitivity without tolerance after peripheral nerve injury. Anesthesiology, 108, 722-734.
77. Sigel, E., Baur, R., Rácz, I., Marazzi, J., Smart, T.G., Zimmer, A. & Gertsch, J. (2011) The major central endocannabinoid directly acts at GABA(A) receptors. Proc. Natl. Acad. Sci. USA, 108, 18150-18155.
78. Starowicz, K. & Di Marzo, V. (2013) Non-psychotropic analgesic drugs from the endocannabinoid system: "Magic bullet" or "multiple-target" strategies? Eur. J. Pharmacol., 716, 41-53.
79. Steiner, M.A., Wanisch, K., Monory, K., Marsicano, G., Borroni, E., Bachili, H., Holsboer, F., Lutz, B. & Wotjak, C.T. (2008) Impaired cannabinoid receptor type 1 signaling interferes with stress-coping behavior in mice. Pharmacogenomics J., 8, 196-208.
80. Tchantchou, F. & Zhang, Y. (2013) Selective inhibition of alpha/beta-hydrolase domain 6 attenuates neurodegeneration, alleviates blood brain barrier breakdown, and improves functional recovery in a mouse model of traumatic brain injury. J. Neurotraum., 30, 565-579.
81. Ueda, N., Tsuboi, K. & Uyama, T. (2010) N-acylethanolamine metabolism with special reference to N-acylethanolamine-hydrolyzing acid amidase (NAAA). Prog. Lipid Res., 49, 299-315.
82. Valenzano, K.J., Tafesse, L., Lee, G., Harrison, J.E., Boulet, J.M., Gottshall, S.L., Mark, L., Pearson, M.S., Miller, W., Shan, S., Rabadi, L., Rotshteyn, Y., Chaffer, S.M., Turchin, P.I., Elsemore, D.A., Toth, M., Koetzner, L. & Whiteside, G.T. (2005) Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy. Neuropharmacology, 48, 658-672.
83. 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.
84. Vincenzi, F., Targa, M., Corciulo, C., Tabrizi, M.A., Merighi, S., Gessi, S., Saponaro, G., Baraldi, P.G., Borea, P.A. & Varani, K. (2013) Antinociceptive effects of the selective CB2 agonist MT178 in inflammatory and chronic rodent pain models. Pain, 154, 864-873.
85. Wallace, V.C., Segerdahl, A.R., Lambert, D.M., Vandevoorde, S., Blackbeard, J., Pheby, T., Hasnie, F. & Rice, A.S. (2007) The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy. Brit. J. Pharmacol., 151, 1117-1128.
86. Walter, L., Franklin, A., Witting, A., Moller, T. & Stella, N. (2002) Astrocytes in culture produce anandamide and other acylethanolamides. J. Biol. Chem., 277, 20869-20876.
87. Watkins, L.R., Milligan, E.D. & Maier, S.F. (2001) Spinal cord glia: new players in pain. Pain, 93, 201-205.
88. Whiteside, G.T., Gottshall, S.L., Boulet, J.M., Chaffer, S.M., Harrison, J.E., Pearson, M.S., Turchin, P.I., Mark, L., Garrison, A.E. & Valenzano, K.J. (2005) A role for cannabinoid receptors, but not endogenous opioids, in the antinociceptive activity of the CB2-selective agonist, GW405833. Eur. J. Pharmacol., 528, 65-72.
89. Witting, A., Walter, L., Wacker, J., Möller, T. & Stella, N. (2004) P2X7 receptors control 2-arachidonoylglycerol production by microglial cells. Proc. Natl. Acad. Sci. USA, 101, 3214-3219.
90. Witting, A., Chen, L., Cudaback, E., Straiker, A., Walter, L., Rickman, B., Möller, T., Brosnan, C. & Stella, N. (2006) Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection. Proc. Natl. Acad. Sci. USA, 103, 6362-6367.
91. Yévenes, G.E. & Zeilhofer, H.U. (2011) Molecular sites for the positive allosteric modulation of glycine receptors by endocannabinoids. PLoS ONE, 6, e23886.
92. Zhang, J., Hoffert, C., Vu, H.K., Groblewski, T., Ahmad, S. & O'Donnell, D. (2003) Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models. Eur. J. Neurosci., 17, 2750-2754.
93. Zhang, F., Challapalli, S.C. & Smith, P.J. (2009) Cannabinoid CB(1) receptor activation stimulates neurite outgrowth and inhibits capsaicin-induced Ca(2+) influx in an in vitro model of diabetic neuropathy. Neuropharmacology, 52, 88-96.
94. Zygmunt, P.M., Petersson, J., Andersson, D.A., Chuang, H., Sørgård, M., Di Marzo, V., Julius, D. & Högestätt, E.D. (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature, 400, 452-457.