Repeated treatment with the synthetic cannabinoid WIN 55,212-2 reduces both hyperalgesia and production of pronociceptive mediators in a rat model of neuropathic pain
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The antinociceptive properties of cannabinoids in persistent pain are not fully elucidated. We investigated the effect of repeated treatment with the synthetic cannabinoid receptor agonist WIN 55,212-2 on the neuropathic pain induced in rats by chronic constriction of the sciatic nerve. WIN 55,212-2 administered daily throughout the development of neuropathy reversed the hyperalgesia, at a dose (0.1 mg x kg(-1), s.c.) that had no effect on the nociceptive responses of either paw contralateral to the sciatic ligation or of animals subjected to sham surgery. At 14 days after injury, the levels of mediators known to be involved in neuropathic pain, such as prostaglandin E2, NO and the neuronal NOS, were increased. Repeated treatment with WIN 55,212-2 abolished these increases. In the light of the current clinical need for neuropathic pain treatments, these findings indicate that cannabinoid agonists, at doses devoid of psychoactive effects, could constitute important compounds for the development of new analgesics.
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WIN55,212-2 normalizes prostaglandin E2 levels and nitric oxide activity, two mediators of neuropathic pain that are increased following CCI.
“WIN55,212-2 also normalizes prostaglandin E2 (PGE2) levels and nitric oxide (NO) activity, two mediators of neuropathic pain that are increased following CCI.48”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [48]
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Cites
Ethical guidelines for investigations of experimental pain in conscious animals.
Zimmermann, M. (1983) · Pain · doi:10.1016/0304-3959(83)90201-4 · Cited by 7,762 · see citing works
A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man
Bennett, G. J., & Xie, Y.-K. (1988) · Pain · doi:10.1016/0304-3959(88)90209-6 · Cited by 5,376 · see citing works
A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia
Hargreaves, K., Dubner, R. A., Brown, F. J., Flores, C., & Joris, J. L. (1988) · Pain · doi:10.1016/0304-3959(88)90026-7 · Cited by 5,155 · see citing works
A Fluorometric Assay for the Measurement of Nitrite in Biological Samples
Misko, T. P., Schilling, R. J., Salvemini, D., Moore, W. M., & Currie, M. G. (1993) · Analytical Biochemistry · doi:10.1006/abio.1993.1449 · Cited by 1,027 · see citing works
Cannabinoid receptors and pain
Pertwee, R. G. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00031-9 · Cited by 741 · see citing works
Ibrahim, M. M., Deng, H., Zvonok, A., Cockayne, D. A., Kwan, J., Mata, H. P., Vanderah, T. W., Lai, J., Porreca, F., Makriyannis, A., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834309100 · Cited by 491 · see citing works
Compton, D. M., Rice, K. C., Costa, B., Razdan, R. K., Melvin, L. S., Johnson, M. R., & Martin, B. R. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)38122-x · Cited by 461 · see citing works
Zhang, J., Hoffert, C., Vu, H. K., Groblewski, T., Ahmad, S., & O'Donnell, D. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02704.x · Cited by 419 · see citing works
Mechanisms of neuropathic pain
Bridges, D., Thompson, S., & Rice, A. S. C. (2001) · British Journal of Anaesthesia · doi:10.1093/bja/87.1.12 · Cited by 403 · see citing works
Fox, A., Kesingland, A., Gentry, C., McNair, K., Patel, S., Urban, L., & James, I. (2001) · Pain · doi:10.1016/s0304-3959(00)00474-7 · Cited by 379 · see citing works
Herzberg, U., Eliav, E., Bennett, G. J., & Kopin, I. J. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(96)13308-5 · Cited by 307 · see citing works
Bridges, D., Ahmad, K., & Rice, A. S. C. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704110 · Cited by 221 · see citing works
Opioids and Chronic Neuropathic Pain
Foley, K. M. (2003) · New England Journal of Medicine · doi:10.1056/nejme030014 · Cited by 139 · see citing works
Ma, W., & Eisenach, J. C. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.01940.x · Cited by 136 · see citing works
Cannabinoid CB1 receptor upregulation in a rat model of chronic neuropathic pain
Siegling, A., Hofmann, H. A., Denzer, D., Mauler, F., & De Vry, J. (2001) · European Journal of Pharmacology · doi:10.1016/s0014-2999(01)00798-1 · Cited by 108 · see citing works
Two distinctive antinociceptive systems in rats with pathological pain
Mao, J., Price, D. D., Lü, J., Keniston, L., & Mayer, D. J. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00998-2 · Cited by 104 · see citing works
Local nitric oxide synthase activity in a model of neuropathic pain
Levy, D., & Zochodne, D. W. (1998) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1998.00186.x · Cited by 104 · see citing works
Nackley, A. G., Suplita, R. L., & Hohmann, A. G. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00870-9 · Cited by 103 · see citing works
Luo, Z. D., Chaplan, S. R., Scott, B., Čı́žková, D., Calcutt, N. A., & Yaksh, T. L. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-21-09201.1999 · Cited by 90 · see citing works
Qi, W.-N., Yan, Z.-Q., Whang, P. G., Zhou, Q., Chen, L., Seaber, A. V., Stamler, J. S., & Urbaniak, J. R. (2001) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2001.281.3.c849 · Cited by 37 · see citing works
Chapman, V. (2001) · Neuropharmacology · doi:10.1016/s0028-3908(01)00125-3 · Cited by 25 · see citing works
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The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pacher, P., Bátkai, S., & Kunos, G. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.2 · Cited by 2,077 · see citing works
“…cannabinoids such as CP55,940 and WIN 55,212-2 are effective against chemical (Sofia et al., 1973; Formukong et al., 1988; Calignano et al., 1998; Costa et al., 2004a,b; Guindon et al., 2006; Ulugol et al., 2006), mechanical (Sofia et al., 1973; Martin et al., 1996; Smith et al., 1998; Guindon…”
BackgroundCannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside
Rahn, E. J., & Hohmann, A. G. (2009) · Neurotherapeutics · doi:10.1016/j.nurt.2009.08.002 · Cited by 305 · see citing works
“127 Cold and mechanical allodynia, but not thermal hyperalgesia, have been reported in a model of autoimmune encephalomyelitis in which mice were immunized with myelin oligodendrocyte glycoprotein (MOG(35-55))128; autoimmune encephalomyelitis has been postulated to underlie the development of neuropathic pain in MS.”
BackgroundDonvito, G., Nass, S. R., Wilkerson, J. L., Curry, Z. A., Schurman, L. D., Kinsey, S. G., & Lichtman, A. H. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.204 · Cited by 301 · see citing works
Pethö, G., & Reeh, P. W. (2012) · Physiological Reviews · doi:10.1152/physrev.00048.2010 · Cited by 288 · see citing works
Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models
Jayamanne, A., Greenwood, R., Mitchell, V. A., Aslan, S., Piomelli, D., & Vaughan, C. W. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706510 · Cited by 287 · see citing works
Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats
Petrosino, S., Palazzo, E., de Novellis, V., Bisogno, T., Rossi, F., Maione, S., & Di Marzo, V. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.08.011 · Cited by 227 · see citing works
Mitrirattanakul, S., Ramakul, N., Guerrero, A. V., Matsuka, Y., Ono, T., Iwase, H., Mackie, K., Faull, K. F., & Spigelman, I. (2006) · Pain · doi:10.1016/j.pain.2006.06.016 · Cited by 207 · see citing works
“Our findings provide an explanation for the persistent effectiveness of peripherally administered CB1R agonists in alleviating the painful symptoms of peripheral neuropathy (Bridges et al., 2001; Fox et al., 2001; Costa et al., 2004).”
BackgroundThe endogenous cannabinoid system and its role in nociceptive behavior
Cravatt, B. F., & Lichtman, A. H. (2004) · Journal of Neurobiology · doi:10.1002/neu.20080 · Cited by 203 · see citing works
“Endocannabinoids and Nociception 151 et al., 2001; Bridges et al., 2001; Fox et al., 2001; Lim et al., 2003; Costa et al., 2004), apparently through both central (Monhemius et al., 2001; Fox et al., 2001; Lim et al., 2003) and peripheral (Fox et al., 2001) mechanisms.”
BackgroundTherapeutic potential of monoacylglycerol lipase inhibitors
Mulvihill, M. M., & Nomura, D. K. (2012) · Life Sciences · doi:10.1016/j.lfs.2012.10.025 · Cited by 199 · see citing works
“In addition to these clinical avenues, both CB1 and CB2 agonists have also been shown to exert anti-nociceptive and anti-inflammatory actions in various rodent models of neuropathic pain and inflammation (Bridges et al., 2001; Costa et al., 2004; Fox et al., 2001; Ibrahim et al., 2003; Kinsey et al., 2011a; Quartilho…”
BackgroundCannabinoids and Pain: Sites and Mechanisms of Action
Starowicz, K., & Finn, D. P. (2017) · Advances in pharmacology · doi:10.1016/bs.apha.2017.05.003 · Cited by 192 · see citing works
“It has been suggested that repeated administration of URB597 may prove to be more efficacious in neuropathic pain models, as observed previously for exogenous cannabinoid receptor agonists (Costa et al., 2004).”
BackgroundRusso, R., LoVerme, J., La Rana, G., Compton, T. R., Parrott, J., Duranti, A., Tontini, A., Mor, M., Tarzia, G., Calignano, A., et al. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.119941 · Cited by 182 · see citing works
“, 2005), as well as with the analgesic effects of cannabinoid agonists (Costa et al., 2004) and gabapentin (Fox et al.”
BackgroundCB1 receptor-deficient mice as a model for depression
Valverde, O., & Torrens, M. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.09.031 · Cited by 153 · see citing works
Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses
Breijyeh, Z., Jubeh, B., Bufo, S. A., Karaman, R., & Scrano, L. (2021) · Toxins · doi:10.3390/toxins13020117 · Cited by 120 · see citing works
“WIN-55,212-2 ((R)-(+)-[2,3-Dihydro-5-methyl-3[(4morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4benzoxazinyl]-(1-naphthalenyl)methanone) (WIN (17), Figure 4) A synthetic cannabinoid that binds non-selectively to CB1 and CB2 receptors Has the ability to alleviate neuropathic pain by suppressing mechanical allodynia and thermal…”
BackgroundLever, I. J., & Rice, A. S. C. (2007) · Springer eBooks · doi:10.1007/978-3-540-33823-9_10 · Cited by 108 · see citing works
Comelli, F., Giagnoni, G., Bettoni, I., Colleoni, M., & Costa, B. (2008) · Phytotherapy Research · doi:10.1002/ptr.2401 · Cited by 103 · see citing works
“In fact, both cannabinoid receptor subtypes (CB1 and CB2) are molecular targets for many THCmediated effects, whereas CBD does not bind to cannabinoid receptors but it displays good affinity for the vanilloid TRPV1 receptor (Bisogno et al., 2001; Costa et al., 2004, 2007).”
InfluentialSelf-citationInvolvement of cannabinoid receptors in gut motility and visceral perception
Hornby, P. J., & Prouty, S. M. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705783 · Cited by 103 · see citing works
“…it has been shown in other systems, such as a neuropathic pain model, that WIN 55,212-2 reduces the hyperalgesia that develops after sciatic nerve ligation and British Journal of Pharmacology vol 141 (8) reduces the levels of pronociceptive substances, such as prostaglandin E2 (Costa et al., 2004).”
BackgroundBurgos, E., Gómez‐Nicola, D., Pascual, D., Martı́n, M. I., Nieto‐Sampedro, M., & Goicoechea, C. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.02.008 · Cited by 99 · see citing works
“The antinociceptive activity of cannabinoid agonists has been widely demonstrated, suggesting a regulatory role in nociceptive pathways (Cravatt and Lichtman, 2004; Martin and Lichtman, 1998; Pertwee, 2001; Rice et al., 2002; Seyrek et al., 2010; Walker and Hohmann, 2005).”
Costa, B., Siniscalco, D., Trovato, A. E., Comelli, F., Sotgiu, M. L., Colleoni, M., Maione, S., Rossi, F., & Giagnoni, G. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706798 · Cited by 99 · see citing works
“Antihyperalgesic and antiallodynic effects of cannabinoids have been demonstrated in several models of experimental neuropathy (Herzberg et al., 1997; Bridges et al., 2001; Fox et al., 2001; Costa et al., 2004a).”
BackgroundPathophysiology and treatment of pain in joint disease☆
Schaible, H., Schmelz, M., & Tegeder, I. (2006) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2006.01.011 · Cited by 98 · see citing works
Dziadulewicz, E. K., Bevan, S., Brain, C. T., Coote, P. R., Culshaw, A. J., Aj, D., Edwards, L. J., Fisher, A. J., Fox, A. J., Gentry, C., et al. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm070317a · Cited by 95 · see citing works
Jhaveri, M. D., Elmes, S. J. R., Richardson, D., Barrett, D. A., Kendall, D. A., Mason, R., & Chapman, V. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06162.x · Cited by 88 · see citing works
“(CB1) agonists attenuate pain behaviour and evoked neuronal responses in neuropathic rats (Fox et al., 2001; Costa et al., 2004; Scott et al., 2004; Sagar et al., 2005; Liu & Walker, 2006).”
BackgroundPalazzo, E., De Novellis, V., Petrosino, S., Marabese, I., Vita, D., Giordano, C., Di Marzo, V., Mangoni, G. S., Rossi, F., & Maione, S. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05086.x · Cited by 86 · see citing works
“Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd European Journal of Neuroscience, 24, 2011–2020 without changing behavioural nociceptive responses (Herzberg et al., 1997; Costa et al., 2004).”
BackgroundMethodResultInfluentialCannabinoid Analgesia as a Potential New Therapeutic Option in the Treatment of Chronic Pain
Burns, T. L., & Ineck, J. R. (2006) · Annals of Pharmacotherapy · doi:10.1345/aph.1g217 · Cited by 84 · see citing works
Hervera, A., Leánez, S., Motterlini, R., & Pol, O. (2013) · Anesthesiology · doi:10.1097/aln.0b013e318286d085 · Cited by 78 · see citing works
Peripherally Selective Cannabinoid 1 Receptor (CB1R) Agonists for the Treatment of Neuropathic Pain
Seltzman, H. H., Shiner, C., Hirt, E. E., Gilliam, A. F., Thomas, B. F., Maitra, R., Snyder, R. W., Black, S. R., Patel, P. R., Mulpuri, Y., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00516 · Cited by 75 · see citing works
Comelli, F., Bettoni, I., Colleoni, M., Giagnoni, G., & Costa, B. (2009) · Phytotherapy Research · doi:10.1002/ptr.2806 · Cited by 75 · see citing works
Vera, G., Chiarlone, A., Cabezos, P. A., Pascual, D., Martín, M. I., & Abalo, R. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.06.012 · Cited by 73 · see citing works
Opioid and cannabinoid synergy in a mouse neuropathic pain model
Kazantzis, N. P., Casey, S. L., Seow, P. W., Mitchell, V. A., & Vaughan, C. W. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13534 · Cited by 71 · see citing works
“…induced by neuropathic pain models in animals but also produce a range of side effects, such as the disruption of motor control, catalepsy, immobility and cognitive impairment (Herzberg et al., 1997; Fox et al., 2001; Lim et al., 2003; Costa et al., 2004; De Vry et al., 2004; Scott et al., 2004).”
BackgroundResultActions of the dual FAAH/MAGL inhibitor JZL195 in a murine neuropathic pain model
Barnes, N. S. A., Mitchell, V. A., Kazantzis, N. P., & Vaughan, C. W. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13337 · Cited by 70 · see citing works
“receptor agonist WIN55212 also had a dose-dependent antiallodynic effect as observed previously for a range of nonselective cannabinoid receptor agonists (Herzberg et al., 1997; Fox et al., 2001; Lim et al., 2003; Costa et al., 2004; De Vry et al., 2004; Scott et al., 2004).”
BackgroundInfluentialHervera, A., Negrete, R., Leánez, S., Martín-Campos, J. M., & Pol, O. (2010) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.167585 · Cited by 64 · see citing works
Malek, N., Mrugala, M., Makuch, W., Kolosowska, N., Przewlocka, B., Binkowski, M., Czaja, M., Morera, E., Di Marzo, V., & Starowicz, K. (2015) · Pain · doi:10.1097/j.pain.0000000000000132 · Cited by 63 · see citing works
“model of acute inflammation in which the TRPV1 antagonist capsazepine reversed the effects of CBD, whereas CB1 (SR141716A)- and CB2 (SR144528)-specific antagonists had no effect.(13) Recently, a noxious effect of FAAH inhibitors, ie, AEAinduced cell death, was observed in human cardiomyocytes.”
BackgroundDoğrul, A., Gül, H., Yıldız, O., Bilgin, F., & Güzeldemir, M. E. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.06.060 · Cited by 61 · see citing works
Shen, J., Fox, L. E., & Cheng, J. (2013) · Pain Medicine · doi:10.1111/pme.12057 · Cited by 60 · see citing works
New Targeted Treatments for Fragile X Syndrome
Protic, D. D., Salcedo‐Arellano, M. J., Dy, J. B. S., Potter, L. A., & Hagerman, R. J. (2019) · Current Pediatric Reviews · doi:10.2174/1573396315666190625110748 · Cited by 57 · see citing works
Desroches, J., Charron, S., Bouchard, J., & Beaulieu, P. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.10.006 · Cited by 51 · see citing works
“It was purchased from Tocris (Ellisville, MO, USA) in a powder form and dissolved in a 1:1:18 mixture of ethanol:cremophor:saline (Costa et al., 2004).”
MethodCannabinoid receptors and pain
Starowicz, K., Małek, N., & Przewłocka, B. (2013) · Wiley Interdisciplinary Reviews Membrane Transport and Signalling · doi:10.1002/wmts.83 · Cited by 50 · see citing works
Expression of opioid receptors and c-fos in CB1 knockout mice exposed to neuropathic pain
Pol, O., Murtra, P., Caracuel, L., Valverde, O., Puig, M. M., & Maldonado, R. J. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.11.002 · Cited by 47 · see citing works
Actions of the endocannabinoid transport inhibitor AM404 in neuropathic and inflammatory pain models
Mitchell, V. A., Greenwood, R., Jayamanne, A., & Vaughan, C. W. (2007) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2007.04692.x · Cited by 43 · see citing works
“previously for the cannabinoid receptor agonist WIN55 212 in a neuropathic pain model.(24,28) Alternatively, the presence of acute AM404 effects in the present study may be due to the use of different neuropathic pain models.”
BackgroundDevelopment and expression of neuropathic pain in CB1 knockout mice
Castañé, A., Célèrier, E., Martín, M., Ledent, C. A., Parmentier, M., Maldonado, R. J., & Valverde, O. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.07.022 · Cited by 42 · see citing works
“THC and synthetic cannabinoids, such as WIN 55,212-2, CP-55,940 and HU-210, alleviated thermal and mechanical hyperalgesia and allodynia associated with chronic constriction injury of the sciatic nerve (Herzberg et al., 1997; Mao et al., 2000; Costa et al., 2004), L5 spinal nerve ligation (Bridges et al.”
BackgroundMaio, R. D., Cannon, J. R., & Greenamyre, J. T. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.10.018 · Cited by 40 · see citing works
Hald, A., Ding, M. L., Egerod, K. L., Hansen, R. B., KONRADSEN, D., JORGENSEN, S., Atalay, B., Nasser, A., Bjerrum, O. J., & Heegaard, A. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.04.021 · Cited by 40 · see citing works
Leichsenring, A., Andriske, M., Bäcker, I., Stichel, C. C., & Lübbert, H. (2009) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-008-0386-4 · Cited by 39 · see citing works
“However, in contrast to CB1/CB2 cannabinoids (Costa et al. 2004; De Vry et al. 2004; Mao et al. 2000; Marchalant et al. 2007), the impact of long-term treatment with CB2 agonists has not been studied so far.”
BackgroundResultEffects of a cannabinoid agonist on spinal nociceptive neurons in a rodent model of neuropathic pain
Liu, C., & Walker, J. M. (2006) · Journal of Neurophysiology · doi:10.1152/jn.00498.2006 · Cited by 37 · see citing works
“These findings are consistent with the antihyperalgesic and antiallodynic effects of cannabinoids in behavioral models of neuropathic pain (Bridges et al. 2001; Costa et al. 2004; Fox et al. 2001; Herzberg et al. 1997; Wallace et al. 2003).”
ResultCannabinoids in pain and inflammation
Mbvundula, E. C., Rainsford, K. D., & Bunning, R. A. D. (2004) · Inflammopharmacology · doi:10.1163/1568560041352275 · Cited by 36 · see citing works
“Repeated treatment with Win-55,212-2 abolished these increases (Costa et al., 2004).”
Hama (2009) · The Journal of Rehabilitation Research and Development · doi:10.1682/jrrd.2008.04.0049 · Cited by 32 · see citing works
“In rats with chronic peripheral neuropathic pain, CB receptor agonists exhibit robust efficacy despite repeated administration [39–40].”
BackgroundŁuszczki, J. J., & Florek-Łuszczki, M. (2012) · Pharmacological Reports · doi:10.1016/s1734-1140(12)70867-8 · Cited by 28 · see citing works
“Moreover, the synthetic cannabinoid WIN attenuated allodynia and hyperalgesia in various rat models of neuropathic pain [6, 10, 20, 31, 33].”
BackgroundCannabinoids may worsen gastric dysmotility induced by chronic cisplatin in the rat
Abalo, R., Cabezos, P. A., Vera, G., López-Pérez, A. E., & Martı́n, M. I. (2013) · Neurogastroenterology & Motility · doi:10.1111/nmo.12073 · Cited by 28 · see citing works
Pre-emptive antinociceptive effects of a synthetic cannabinoid in a model of neuropathic pain
Guindon, J., Desroches, J., Dani, M., & Beaulieu, P. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.04.060 · Cited by 24 · see citing works
Banister, S. D., Kumar, K. K., Kumar, V., Kobilka, B. K., & Malhotra, S. V. (2019) · MedChemComm · doi:10.1039/c8md00595h · Cited by 22 · see citing works
Eicosanoid mediation of cannabinoid actions
BURSTEIN, S. H. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.05.018 · Cited by 22 · see citing works
Novel targets for Spinal Cord Injury related neuropathic pain
Ahmed, M. M., King, K. C., Pearce, S. M., Ramsey, M. A., Miranpuri, G. S., & Resnick, D. K. (2011) · Annals of Neurosciences · doi:10.5214/ans.0972.7531.1118413 · Cited by 22 · see citing works
Cascio, M. G., Bisogno, T., Palazzo, E., Thomas, A., van der Stelt, M., Brizzi, A., de Novellis, V., Marabese, I., Ross, R. A., van de Doelen, T., et al. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706888 · Cited by 22 · see citing works
“Finally, although activation of CB2 causes pain relief (Costa et al., 2004; Ibrahim et al., 2006), recent evidence also points to cannabinoid CB2 receptor antagonists/inverse agonists as promising antiinflammatory agents (Iwamura et al., 2001; Ueda et al., 2005; Lunn et al., 2006; Oka et al., 2006).”
BackgroundPreclinical science regarding cannabinoids as analgesics: An overview
Lynch, M. (2005) · Pain Research and Management · doi:10.1155/2005/169093 · Cited by 20 · see citing works
“Furthermore, repeated administration of WIN55,212-2 given subcutaneously reversed the development of hyperalgesia that normally develops in chronic constriction of the sciatic nerve in rats (67), supporting that cannabinoids may play a role in prevention of neuropathic pain if given early after nerve injury.”
BackgroundThe endocannabinoid and endovanilloid systems and their interactions in neuropathic pain
Maione, S., Starowicz, K., Palazzo, E., Rossi, F., & Marzo, V. D. (2006) · Drug Development Research · doi:10.1002/ddr.20098 · Cited by 21 · see citing works
“Stimulation of CB2 receptors by WIN 55,212-2 would indeed reduce the release of those mediators responsible for peripheral nociceptor sensitization [Costa et al., 2004a], thus supporting the evidence that treatment with cannabinoids indirectly inhibits neuropathic pain and the peripheral neurogenic…”
InfluentialZhu, C. Z., Mikusa, J., Fan, Y., Hollingsworth, P. R., Pai, M., Chandran, P., Daza, A. V., Yao, B., Dart, M. J., Meyer, M., et al. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00184.x · Cited by 21 · see citing works
“…(CFA)-induced inflammatory pain, formalininduced persistent nociception (Tsou et al., 1996; Martin et al., 1999), and neuropathic pain caused by peripheral nerve injury (Fox et al., 2001; Costa et al., 2004), toxic nerve damage (Pascual et al., 2005) and diabetic neuropathy (Dogrul et al., 2004).”
BackgroundInfluentialBujalska, M. (2008) · Pharmacology · doi:10.1159/000156485 · Cited by 20 · see citing works
Neuropathic pain: strategies in drug discovery and treatment
Yogeeswari, P., Ragavendran, J. V., & Sriram, D. (2007) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2.2.169 · Cited by 20 · see citing works
“[85] investigated the effects of repeated treatments with compound 48 on both hyperalgesia and production of pronociceptive mediators in a rat model of neuropathic pain.”
BackgroundBujalska‐Zadrożny, M., de Cordé, A., & Pawlik, K. (2014) · Pharmacological Reports · doi:10.1016/j.pharep.2014.08.023 · Cited by 19 · see citing works
Alterations in the Anandamide Metabolism in the Development of Neuropathic Pain
Małek, N., Kucharczyk, M. W., & Starowicz, K. (2014) · BioMed Research International · doi:10.1155/2014/686908 · Cited by 19 · see citing works
Cannabinoids in anaesthesia and pain therapy
Azad, S. C., & Rammes, G. (2005) · Current Opinion in Anaesthesiology · doi:10.1097/01.aco.0000174959.05383.9c · Cited by 19 · see citing works
The endocannabinoid system as a therapeutic target in neuropathic pain: a review
Quintero, J.-M., Díaz, L. E., Galve‐Roperh, I., Bustos, R., Leon, M.-X., Beltran, S., & Dodd, S. (2024) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2024.2407824 · Cited by 18 · see citing works
“For example, Costa et al . observed that repeated treatment with WIN 55,212-2 abolished the increase in levels of mediators known to be involved in neuropathic pain, such as prostaglandin E2, nNOS-neuronal enzyme [88].”
Spyridakos, D., Papadogkonaki, S., Dionysopoulou, S., Mastrodimou, N., Polioudaki, H., & Thermos, K. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104907 · Cited by 17 · see citing works
Lever, I. J., Pheby, T., & Rice, A. S. C. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707210 · Cited by 17 · see citing works
“However, previous reports have demonstrated the efficacy of peripherally administered WIN 55,212–2 to evoke antihypersensitivity effects when initiated either 1 day or 12–15 days after the establishment of a nerve injury (Fox et al., 2001; Costa et al., 2004).”
BackgroundSlivicki, R. A., Yi, J., Brings, V. E., Huynh, P. N., & Gereau, R. W. (2021) · Pain · doi:10.1097/j.pain.0000000000002550 · Cited by 15 · see citing works
Hama, A. T., Germano, P., Varghese, M. S., Cravatt, B. F., Milne, G. T., Pearson, J. P., & Sagen, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096396 · Cited by 15 · see citing works
“A number of preclinical neuropathic pain studies have demonstrated marked antinociception following both acute and repeated activation of CB receptors, which appears to be in part mediated through the CB1 receptor [3,20,34–38].”
Role of Cannabinoid Receptors in Crocin-Induced Hypoalgesia in Neuropathic Pain in Rats
Vafaei, A. A., Safakhah, H. A., Jafari, S., Tavasoli, A., Rashidy‐Pour, A., Ghanbari, A., Seyedinia, S. A., & Tarahomi, P. (2020) · Journal of Experimental Pharmacology · doi:10.2147/jep.s250738 · Cited by 14 · see citing works
Dönertaş, B., Ünel, Ç. Ç., & Erol, K. (2018) · Journal of Experimental Pharmacology · doi:10.2147/jep.s162059 · Cited by 14 · see citing works
“54 All these mediators may lead to attenuate the early production of spinal proinflammatory cytokines interleukin (IL)-1 β , IL-6 and tumor necrosis factor (TNF)- α .”
Metabotropic Glutamate and Cannabinoid Receptor Crosstalk in Periaqueductal Grey Pain Processing
Palazzo, E., de Novellis, V., Marabese, I., Rossi, F., & Maione, S. (2006) · Current Neuropharmacology · doi:10.2174/157015906778019545 · Cited by 12 · see citing works
“Cannabinoids are similar to opioids in alleviating pain and, under some conditions such as neuropathic pain, they show even greater potency and efficacy than opioids [7,15, 28,35,43,51,87].”
Nascimento, G. C., Escobar-Espinal, D. M., Bálico, G. G., da Silva, N. R., & Del-Bel, E. (2024) · International review of neurobiology · doi:10.1016/bs.irn.2024.04.016 · Cited by 13 · see citing works
Spigelman, I. (2009) · Frontiers in neuroscience · doi:10.1201/9781439812105-c5 · Cited by 12 · see citing works
Effect of acute topical application of (+)-pentazocine on the mechanical allodynia in diabetic mice
Ohsawa, M., Hayashi, S.-S., & Kamei, J. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.05.005 · Cited by 9 · see citing works
“The contents of hindpaw NO in nerve-injured and inflammated animal were consistently increased, and inhibition of NO production could ameliorate the hyperalgesia and allodynia in these animals (Omote et al., 2001; Costa et al., 2004; Chu et al., 2005).”
BackgroundTeuchmann, H. L., Hogri, R., Heinke, B., & Sandkühler, J. (2022) · Journal of Pain · doi:10.1016/j.jpain.2022.03.234 · Cited by 7 · see citing works
Hama, A. T., Pearson, J. P., & Sagen, J. (2014) · Pharmacology Research & Perspectives · doi:10.1002/prp2.34 · Cited by 7 · see citing works
“The issue of tolerance could in part be due to the model as well as due to the pharmacological properties of the drug (Costa et al. 2004; De Vry et al. 2004a).”
Cavalcante, M. L. D. S., Silva, M. S., Cavalcante, A. K. M., Santos, R. D. O., Nunes, D. D. T., Busquets, S., Argilés, J. M. A., Seelaender, M. C. L., Neto, E. M. D. M., dos Santos, A. A., et al. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173087 · Cited by 6 · see citing works
Modulation of Pain by Endocannabinoids in the Periphery
Uhelski, M. L., Khasabova, I. A., & Simone, D. A. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.79673 · Cited by 5 · see citing works
“In studies of peripheral neuropathy produced by chemotherapy, WIN 55,212-2 prevented the development of neuropathy induced by cisplatin treatment [33], and when WIN 55,212-2 treatment was initiated after sciatic nerve ligation (CCI model of neuropathic pain), mechanical hyperalgesia failed to develop by 14 days post-i…”
BackgroundLinde, L. D., Ogryzlo, C. M., Choles, C. M., Cairns, B. E., & Kramer, J. L. K. (2022) · Regional Anesthesia & Pain Medicine · doi:10.1136/rapm-2021-102719 · Cited by 4 · see citing works
Recent data on cannabinoids and their pharmacological implications in neuropathic pain.
Coman, O. A., Păunescu, H., Coman, L., Bădărău, A., & Fulga, I. (2008) · PubMed Central · Cited by 3 · see citing works
Pelorosso, F. G., Gago, J. E., del Rey, G., Menéndez, S. D., Errasti, A. E., & Rothlin, R. P. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.10.058 · Cited by 3 · see citing works
“At the same time, recent animal studies indicate that several cannabinoid ligands are very effective against pain of neuropathic origin (Bridges et al., 2001; Costa et al., 2004; Guindon and Beaulieu, 2006; Herzberg et al., 1997).”
BackgroundNew Insights on Neuropathic Pain Mechanisms as a Source for Novel Therapeutical Strategies
Maione, S., Palazzo, E., Guida, F., Luongo, L., Siniscalco, D., Marabese, I., Rossi, F., & de, V. (2013) · InTech eBooks · doi:10.5772/55276 · Cited by 1 · see citing works
“[102] Costa, B, Colleoni, M, Conti, S, Trovato, A.”
BackgroundThe Management of Neuropathic Pain
Toth, C., & Moulin, D. E. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9781139152211.019 · Cited by 1 · see citing works
Pharmacotherapy of chronic orofacial pain
Benoliel, R., & Sharav, Y. (2008) · Elsevier eBooks · doi:10.1016/b978-0-7234-3412-2.10016-1 · Cited by 1 · see citing works
The Treatment of Neuropathic Pain with Cannabinoid Based Nanotechnology
Linsell, O. (2013) · Otago University Research Archive (University of Otago)
Cannabinoid modulation of nociception and nociceptor activity during inflammation.
Potenzieri, C. (2009) · University of Minnesota Digital Conservancy (University of Minnesota)
Ware, M. A. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9781139152211.022
Maher, D. P., Shah, B. J., & Vorobeychik, Y. (2019) · Springer eBooks · doi:10.1007/978-3-030-27447-4_19 · Cited by 1 · see citing works
Rice, A. S. C. (2007) · Elsevier eBooks · doi:10.1016/b978-84-8174-949-6.50034-4
Rice, A. S. C. (2006) · Elsevier eBooks · doi:10.1016/b0-443-07287-6/50039-4
Liu, L., Wu, C., Xia, H., Cheng, J., Zhong, L., & Wu, J. (2026) · Brain and Behavior · doi:10.1002/brb3.71837
“This behavioral pattern is consistent with previous studies showing that WIN55,212-2 alleviates thermal and mechanical hyperalgesia or allodynia in rat CCI models of neuropathic pain (Herzberg et al. 1997 ; Costa et al. 2003 ).”
- Authors
- Costa, B., Colleoni, M., Conti, S., Trovato, A. E., Bianchi, M., Sotgiu, M. L., & Giagnoni, G.
- Affiliations
- University of Milano-Bicocca (IT)
- University of Milan (IT)
- National Research Council (IT)
- Corresponding author
- Costa, B
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2004-01
- Volume
- 141
- Issue
- 1
- Pages
- 4-8
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1574173
- OpenAlex
- W2048760742
- Cited by
- 89
- References
- 21
- Citations by year
- 2026: 1 · 2024: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 9 · 2012: 4
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- WIN 55,212-2, synthetic cannabinoids, neuropathic pain, chronic constriction injury, sciatic nerve, hyperalgesia, antinociception, prostaglandin E2, nitric oxide, neuronal nitric oxide synthase, cannabinoid receptor agonists, analgesic drug development
- MeSH terms
- Analgesics, Animals, Cannabinoids, Disease Models, Animal, Drug Administration Schedule, Hot Temperature, Hyperalgesia, Injections, Subcutaneous, Male, Morpholines, Naphthalenes, Nitric Oxide, Nociceptors, Pain Measurement, Sciatic Nerve, Time Factors, Dinoprostone, Rats, Wistar, Nitric Oxide Synthase, Sciatic Neuropathy, Receptors, Cannabinoid, Benzoxazines, Rats, Nitric Oxide Synthase Type I
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