Cited by 795Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsNeuropeptides and Animal Physiology

The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.

An endocannabinoid mechanism for stress-induced analgesia

Open access

Hohmann, Andrea G., Suplita, Richard L., Bolton, Nathan M., Neely, Mark H., Fegley, Darren, Mangieri, Regina, Krey, Jocelyn F., Michael Walker, J., Holmes, Philip V., Crystal, Jonathon D., Duranti, Andrea, Tontini, Andrea, Mor, Marco, Tarzia, Giorgio, Piomelli, Daniele·2005·Nature

DOI 10.1038/nature03658

Open this paper in CoChat — free account

Abstract

Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB(1) receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol (2-AG) and anandamide. A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase, selectively increases 2-AG concentrations and, when injected into the periaqueductal grey matter, enhances stress-induced analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating enzyme fatty-acid amide hydrolase, which selectively elevate anandamide concentrations, exert similar effects. Our results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia. These studies also identify monoacylglycerol lipase as a previously unrecognized therapeutic target.

Integrity signals

Registry

Crossref · 10.1038/nature03658

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor
Devane, W. A., Hanuš, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R. (1992) · Science · doi:10.1126/science.1470919 · Cited by 5,633
Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors
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., et al. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(95)00109-d · Cited by 2,913
Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study
Herkenham, M., Lynn, A., Johnson, M., Melvin, L., de Costa, B., & Rice, K. (1991) · The Journal of Neuroscience · doi:10.1523/jneurosci.11-02-00563.1991 · Cited by 2,159
Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides
Cravatt, B. F., Giang, D. K., Mayfield, S. P., Boger, D. L., Lerner, R. A., & Gilula, N. B. (1996) · Nature · doi:10.1038/384083a0 · Cited by 2,125
The molecular logic of endocannabinoid signalling
Piomelli, D. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1247 · Cited by 1,957
Self-citation
Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system
Tsou, K., Brown, S., Sañudo-Peña, M. C., Mackie, K., & Walker, J. M. (1998) · Neuroscience · doi:10.1016/s0306-4522(97)00436-3 · Cited by 1,586
A second endogenous cannabinoid that modulates long-term potentiation
Stella, N., Schweitzer, P., & Piomelli, D. (1997) · Nature · doi:10.1038/42015 · Cited by 1,496
Self-citation
Brain monoglyceride lipase participating in endocannabinoid inactivation
Dinh, T. P., Carpenter, D., Leslie, F. M., Freund, T. F., Katona, I., Sensi, S. L., Kathuria, S., & Piomelli, D. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152334899 · Cited by 1,373
Self-citation
Modulation of anxiety through blockade of anandamide hydrolysis
Kathuria, S., Gaetani, S., Fegley, D., Valiño, F., Duranti, A., Tontini, A., Mor, M., Tarzia, G., Rana, G. L., Calignano, A., et al. (2003) · Nature Medicine · doi:10.1038/nm803 · Cited by 1,293
Self-citation
Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice
Zimmer, A., Zimmer, A. M., Hohmann, A. G., Herkenham, M. A., & Bonner, T. I. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5780 · Cited by 1,078
Self-citation

Flagged first, then by citations

Show all 30 references

1 of the 30 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

Walker, J. M. & Hohmann, A. G. in Cannabinoids—Handbook of Experimental Pharmacology (ed. Pertwee, R.) 509–554 (Springer, Berlin, 2005)

Sorted by citations

Items 101–200 of 795

Anandamide and other N-acylethanolamines: A class of signaling lipids with therapeutic opportunities
Mock, E. D., Gagestein, B., & van der Stelt, M. (2022) · Progress in Lipid Research · doi:10.1016/j.plipres.2022.101194 · Cited by 164
β-arrestins: regulatory role and therapeutic potential in opioid and cannabinoid receptor-mediated analgesia
Raehal, K. M., & Bohn, L. M. (2014) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-41199-1_22 · Cited by 154
“2005), CB1 receptors (CB1R) in the central nervous system play the most pronounced role in mediating the analgesic, motor, and psychoactive effects of cannabinoids (Zimmer et al. 1999; Kelly and Chapman 2001; Hohmann et al. 2005; Pertwee 2005; Suplita et al. 2006; Dziaduleqicz et al. 2007).”
Background
Synthesis and Evaluation of Benzothiazole-Based Analogues as Novel, Potent, and Selective Fatty Acid Amide Hydrolase Inhibitors
Wang, X., Sarris, K., Kage, K., Zhang, D., Brown, S. P., Kolasa, T., Surowy, C. S., El-Kouhen, O. F., Muchmore, S. W., Brioni, J. D., et al. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm801042a · Cited by 154
Prostaglandin E 2 glycerol ester, an endogenous COX‐2 metabolite of 2‐arachidonoylglycerol, induces hyperalgesia and modulates NFκB activity
Hu, S. S., Bradshaw, H. B., Chen, J. S., Tan, B., & Walker, J. M. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.33 · Cited by 151
Monoglyceride lipase as a drug target: At the crossroads of arachidonic acid metabolism and endocannabinoid signaling
Grabner, G. F., Zimmermann, R., Schicho, R., & Taschler, U. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.033 · Cited by 153
Don't Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection of Stress and Reward
Volkow, N. D., Hampson, A. J., & Baler, R. (2016) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104615 · Cited by 159
Anxiolytic-like effect of cannabinoids injected into the rat dorsolateral periaqueductal gray
Moreira, F. A., de Aguiar, D. C., & Guimarães, F. S. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.10.013 · Cited by 153
Synthesis and in Vitro Evaluation of N-Substituted Maleimide Derivatives as Selective Monoglyceride Lipase Inhibitors
Matuszak, N., Muccioli, G. G., Labar, G., & Lambert, D. M. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm900461w · Cited by 147
Endocannabinoid metabolism and uptake: novel targets for neuropathic and inflammatory pain
Jhaveri, M. D., Richardson, D. S., & Chapman, V. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707433 · Cited by 147
Opposite action of hippocampal CB1 receptors in memory reconsolidation and extinction
de Oliveira Alvares, L., Pasqualini Genro, B., Diehl, F., Molina, V. A., & Quillfeldt, J. A. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.05.005 · Cited by 143
Monoacylglycerol lipase (MAGL) as a promising therapeutic target
Gil-Ordóñez, A., Martín‐Fontecha, M., Ortega‐Gutiérrez, S., & López-Rodríguez, M. L. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.07.036 · Cited by 146
Communication networks in the brain: neurons, receptors, neurotransmitters, and alcohol.
Lovinger, D. M. (2008) · Europe PMC (PubMed Central) · Cited by 137
Acute restraint stress enhances hippocampal endocannabinoid function via glucocorticoid receptor activation
Wang, M., Hill, M. N., Zhang, L., Gorzalka, B. B., Hillard, C. J., & Alger, B. E. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881111409606 · Cited by 137
Stress regulates endocannabinoid-CB1 receptor signaling
Hillard, C. J. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.04.001 · Cited by 144
The Endocannabinoid Signaling System in the CNS
Hillard, C. J. (2015) · International review of neurobiology · doi:10.1016/bs.irn.2015.10.001 · Cited by 144
Tac1-Expressing Neurons in the Periaqueductal Gray Facilitate the Itch-Scratching Cycle via Descending Regulation
Gao, Z., Chen, W., Liu, M., Chen, X., Wan, L., Zhang, X., Yuan, L., Lin, J.-K., Wang, M., Zhou, L., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.11.010 · Cited by 136
Endocannabinoid 2-Arachidonoylglycerol Protects Neurons by Limiting COX-2 Elevation
Zhang, J., & Chen, C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800524200 · Cited by 136
The complications of promiscuity: endocannabinoid action and metabolism
Alexander, S. P. H., & Kendall, D. A. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707456 · Cited by 136
Inhibition of COX‐2 expression by endocannabinoid 2‐arachidonoylglycerol is mediated via PPAR‐γ
Du, H., Chen, X., Zhang, J., & Chen, C. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01444.x · Cited by 136
Role of the endocannabinoid system in depression and suicide
Vinod, K. Y., & Hungund, B. L. (2006) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2006.08.006 · Cited by 132
Cannabinoid Type-1 Receptor Reduces Pain and Neurotoxicity Produced by Chemotherapy
Khasabova, I. A., Khasabov, S., Paz, J., Harding-Rose, C., Simone, D. A., & Seybold, V. S. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0403-12.2012 · Cited by 129
Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation
Kasatkina, L. A., Rittchen, S., & Sturm, E. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115431 · Cited by 133
More surprises lying ahead. The endocannabinoids keep us guessing
Piomelli, D. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.07.026 · Cited by 128
Self-citation
In vivo characterization of the highly selective monoacylglycerol lipase inhibitor KML 29: antinociceptive activity without cannabimimetic side effects
Ignatowska‐Jankowska, B. M., Ghosh, S., Crowe, M. S., Kinsey, S. G., Niphakis, M. J., Abdullah, R. A., Tao, Q., O' Neal, S. T., Walentiny, D. M., Wiley, J. L., et al. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12298 · Cited by 128
Biosynthesis and degradation of the endocannabinoid 2‐arachidonoylglycerol
Ueda, N., Tsuboi, K., Uyama, T., & Ohnishi, T. (2010) · BioFactors · doi:10.1002/biof.131 · Cited by 133
The monoacylglycerol lipase inhibitor JZL184 suppresses inflammatory pain in the mouse carrageenan model
Ghosh, S., Wise, L. E., Chen, Y., Gujjar, R., Mahadevan, A., Cravatt, B. F., & Lichtman, A. H. (2013) · Life Sciences · doi:10.1016/j.lfs.2012.06.020 · Cited by 127
TRP Channel Cannabinoid Receptors in Skin Sensation, Homeostasis, and Inflammation
Caterina, M. J. (2014) · ACS Chemical Neuroscience · doi:10.1021/cn5000919 · Cited by 126
Immunohistochemical description of the endogenous cannabinoid system in the rat cerebellum and functionally related nuclei
Suárez, J., Bermúdez‐Silva, F. J., Mackie, K., Ledent, C. A., Zimmer, A., Cravatt, B. F., & de Fonseca, F. R. (2008) · The Journal of Comparative Neurology · doi:10.1002/cne.21774 · Cited by 126
Anandamide and 2-arachidonoylglycerol: Pharmacological Properties, Functional Features, and Emerging Specificities of the Two Major Endocannabinoids
Luchicchi, A., & Pistis, M. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8299-0 · Cited by 130
Peripheral antinociceptive effects of inhibitors of monoacylglycerol lipase in a rat model of inflammatory pain
Guindon, J., Guijarro, A. I., Piomelli, D., & Hohmann, A. G. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01192.x · Cited by 120
Self-citation
Inhibitors of Endocannabinoid-Metabolizing Enzymes Reduce Precipitated Withdrawal Responses in THC-Dependent Mice
Schlosburg, J. E., Carlson, B. L. A., Ramesh, D., Abdullah, R. A., Long, J. Z., Cravatt, B. F., & Lichtman, A. H. (2009) · The AAPS Journal · doi:10.1208/s12248-009-9110-7 · Cited by 120
CB1 Cannabinoid Receptor Signaling and Biased Signaling
Leo, L. M., & Abood, M. E. (2021) · Molecules · doi:10.3390/molecules26175413 · Cited by 121
Discovery of Potent and Reversible Monoacylglycerol Lipase Inhibitors
King, A. R., Dotsey, E. Y., Lodola, A., Jung, K., Ghomian, A., Qiu, Y., Fu, J., Mor, M., & Piomelli, D. (2009) · Chemistry & Biology · doi:10.1016/j.chembiol.2009.09.012 · Cited by 117
Self-citation
Therapeutic Potential of Fatty Acid Amide Hydrolase, Monoacylglycerol Lipase, and N-Acylethanolamine Acid Amidase Inhibitors
Tuo, W., Leleu‐Chavain, N., Spencer, J., Sansook, S., Millet, R., & Chavatte, P. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00538 · Cited by 116
Anandamide, Acting via CB2 Receptors, Alleviates LPS-Induced Neuroinflammation in Rat Primary Microglial Cultures
Małek, N., Popiołek-Barczyk, K., Mika, J., Przewłocka, B., & Starowicz, K. (2015) · Neural Plasticity · doi:10.1155/2015/130639 · Cited by 114
Activation of the endocannabinoid system by organophosphorus nerve agents
Nomura, D. K., Blankman, J. L., Simon, G. M., Fujioka, K., Issa, R. S., Ward, A. M., Cravatt, B. F., & Casida, J. E. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.86 · Cited by 112
Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat
Cippitelli, A., Cannella, N., Braconi, S., Duranti, A., Tontini, A., Bilbao, A., de Fonseca, F. R., Piomelli, D., & Ciccocioppo, R. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1104-0 · Cited by 114
Self-citation
Chronic Psychoemotional Stress Impairs Cannabinoid-Receptor-Mediated Control of GABA Transmission in the Striatum
Rossi, S., Chiara, V. D., Musella, A., Kusayanagi, H., Mataluni, G., Bernardi, G., Usiello, A., & Centonze, D. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5346-07.2008 · Cited by 119
Endocannabinoid Signaling in the Control of Social Behavior
Don, W., Allsop, S. A., Tye, K. M., & Piomelli, D. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2017.04.005 · Cited by 120
Self-citation
The Multifaceted Role of Epoxide Hydrolases in Human Health and Disease
Gautheron, J., & Jéru, I. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010013 · Cited by 111
Modulation of anxiety-like behaviour by Transient Receptor Potential Vanilloid Type 1 (TRPV1) channels located in the dorsolateral periaqueductal gray
Terzian, A. L. B., de Aguiar, D. C., Guimarães, F. S., & Moreira, F. A. (2008) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2008.11.004 · Cited by 111
Cannabinoids and the Brain
Köfalvi, A. (2007) · Springer eBooks · doi:10.1007/978-0-387-74349-3 · Cited by 110
A Review on the Monoacylglycerol Lipase: At the Interface Between Fat and Endocannabinoid Signalling
Labar, G., Wouters, J., & Lambert, D. M. (2010) · Current Medicinal Chemistry · doi:10.2174/092986710791859414 · Cited by 111
An endocannabinoid mechanism in relapse to drug seeking: A review of animal studies and clinical perspectives
Fattore, L., Spano, M. S., Deiana, S., Melis, V., Cossu, G., Fadda, P., & Fratta, W. (2006) · Brain Research Reviews · doi:10.1016/j.brainresrev.2006.05.003 · Cited by 110
Regulation of Inflammatory Pain by Inhibition of Fatty Acid Amide Hydrolase
Naidu, P. S., Kinsey, S. G., Guo, T. L., Cravatt, B. F., & Lichtman, A. H. (2010) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.164806 · Cited by 108
Cannabinoids and Pain
Lever, I. J., & Rice, A. S. C. (2007) · Springer eBooks · doi:10.1007/978-3-540-33823-9_10 · Cited by 108
URB602 Inhibits Monoacylglycerol Lipase and Selectively Blocks 2-Arachidonoylglycerol Degradation in Intact Brain Slices
King, A. R., Duranti, A., Tontini, A., Rivara, S., Rosengarth, A., Clapper, J. R., Astarita, G., Geaga, J. A., Luecke, H., Mor, M., et al. (2007) · Chemistry & Biology · doi:10.1016/j.chembiol.2007.10.017 · Cited by 108
Self-citation
FAAH and anandamide: is 2-AG really the odd one out?
Marzo, V. D., & Maccarrone, M. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.03.001 · Cited by 109
Brain activity of anandamide: a rewarding bliss?
Scherma, M., Masia, P., Satta, V., Fratta, W., Fadda, P., & Tanda, G. (2018) · Acta Pharmacologica Sinica · doi:10.1038/s41401-018-0075-x · Cited by 114
CAY10499, a Novel Monoglyceride Lipase Inhibitor Evidenced by an Expeditious MGL Assay
Muccioli, G. G., Labar, G., & Lambert, D. M. (2008) · ChemBioChem · doi:10.1002/cbic.200800428 · Cited by 106
Functional Redundancy Between Canonical Endocannabinoid Signaling Systems in the Modulation of Anxiety
Bedse, G., Hartley, N. D., Neale, E., Gaulden, A. D., Patrick, T. A., Kingsley, P. J., Uddin, M. J., Plath, N., Marnett, L. J., & Patel, S. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.03.002 · Cited by 108
Inhibition of fatty-acid amide hydrolase enhances cannabinoid stress-induced analgesia: Sites of action in the dorsolateral periaqueductal gray and rostral ventromedial medulla
Suplita, R. L., Farthing, J. N., Gutierrez, T., & Hohmann, A. G. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.07.007 · Cited by 104
Self-citation
Cannabinoid signaling in health and disease
Lu, Y., & Anderson, H. D. (2017) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2016-0346 · Cited by 105
Acute Stress Contributes to Individual Differences in Pain and Pain-Related Brain Activity in Healthy and Chronic Pain Patients
Vachon‐Presseau, É., Martel, M. O., Roy, M., Caron, E., Albouy, G., Marin, M., Plante, I., Sullivan, M. J. L., LUPIEN, S. J., & Rainville, P. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4584-12.2013 · Cited by 105
The antinociceptive effects of intraplantar injections of 2‐arachidonoyl glycerol are mediated by cannabinoid CB2receptors
Guindon, J., Desroches, J., & Beaulieu, P. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706990 · Cited by 102
Structure of Human N -Acylphosphatidylethanolamine-Hydrolyzing Phospholipase D: Regulation of Fatty Acid Ethanolamide Biosynthesis by Bile Acids
Magotti, P., Bauer, I., Igarashi, M., Babagoli, M. A., Marotta, R., Piomelli, D., & Garau, G. (2015) · Structure · doi:10.1016/j.str.2014.12.018 · Cited by 100
Self-citation
Impact of stress, fear and anxiety on the nociceptive responses of larval zebrafish
López-Luna, J., Al-Jubouri, Q., Al‐Nuaimy, W., & Sneddon, L. U. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181010 · Cited by 99
Differential role of the hippocampal endocannabinoid system in the memory consolidation and retrieval mechanisms
Alvares, L. D. O., Genro, B. P., Diehl, F., & Quillfeldt, J. A. (2008) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2008.01.009 · Cited by 99
Endocannabinoids: The silent partner of glucocorticoids in the synapse
Hill, M. N., & McEwen, B. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901519106 · Cited by 98
The inhibition of monoacylglycerol lipase by URB602 showed an anti‐inflammatory and anti‐nociceptive effect in a murine model of acute inflammation
Comelli, F., Giagnoni, G., Bettoni, I., Colleoni, M., & Costa, B. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707425 · Cited by 97
Modulation of neuropathic and inflammatory pain by the endocannabinoid transport inhibitor AM404 [N-(4-hydroxyphenyl)-eicosa-5,8,11,14-tetraenamide]
La Rana, G., Russo, R., Campolongo, P., Bortolato, M., Mangieri, R. A., Cuomo, V., Iacono, A., Raso, G. M., Meli, R., Piomelli, D., et al. (2006) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.100792 · Cited by 97
“…blockade enhances pain behaviors in several pain models (Calig-nano et al., 1998; Strangman et al., 1998; for contrasting results, see Beaulieu et al., 2000) and abrogates nonopioid stress-induced analgesia (Hohmann et al., 2005), suggesting the existence of an analgesic endocannabinoid tone.”
BackgroundInfluentialSelf-citation
Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI
Chin, C.-L., Tovcimak, A. E., Hradil, V. P., Seifert, T. R., Hollingsworth, P. R., Chandran, P., Zhu, C. Z., Gauvin, D. M., Pai, M., Wetter, J. B., et al. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707506 · Cited by 96
Lack of selectivity of URB602 for 2‐oleoylglycerol compared to anandamide hydrolysis in vitro
Vandevoorde, S., Jonsson, K., Labar, G., Persson, E., Lambert, D. M., & Fowler, C. J. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706971 · Cited by 96
Monoacylglycerol lipase – a target for drug development?
Fowler, C. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01950.x · Cited by 96
AM251, a selective antagonist of the CB1 receptor, inhibits the induction of long-term potentiation and induces retrograde amnesia in rats
Alvares, L. D. O., Genro, B. P., Breda, R. V., Pedroso, M. F., da Costa, J. C., & Quillfeldt, J. A. (2006) · Brain Research · doi:10.1016/j.brainres.2005.11.101 · Cited by 95
Anatomical Distribution of Receptors, Ligands and Enzymes in the Brain and in the Spinal Cord: Circuitries and Neurochemistry
Marsicano, G., & Kuner, R. (2007) · Springer eBooks · doi:10.1007/978-0-387-74349-3_10 · Cited by 103
Molecular architecture of endocannabinoid signaling at nociceptive synapses mediating analgesia
Nyilas, R., Gregg, L. C., Mackie, K., Watanabe, M., Zimmer, A., Hohmann, A. G., & Katona, I. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06751.x · Cited by 94
Self-citation
N-Palmitoyl Glycine, a Novel Endogenous Lipid That Acts As a Modulator of Calcium Influx and Nitric Oxide Production in Sensory Neurons
Rimmerman, N., Bradshaw, H. B., Hughes, V., Chen, J. S.-C., Hu, S. S., McHugh, D., Vefring, E., Jahnsen, J. A., Thompson, E. L., Masuda, K. R., et al. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.045997 · Cited by 96
Endocannabinoid-mediated synaptic plasticity and addiction-related behavior
Sidhpura, N., & Parsons, L. H. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.05.034 · Cited by 92
The endocannabinoid system as a target for the treatment of cannabis dependence
Clapper, J. R., Mangieri, R. A., & Piomelli, D. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.018 · Cited by 94
Self-citation
The endocannabinoid system in the rat dorsolateral periaqueductal grey mediates fear‐conditioned analgesia and controls fear expression in the presence of nociceptive tone
Olango, W., Roche, M., Ford, G., Harhen, B., & Finn, D. P. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01478.x · Cited by 93
Role of Cannabinoids in the Treatment of Pain and (Painful) Spasticity
Karst, M., Wippermann, S., & Ahrens, J. (2010) · Drugs · doi:10.2165/11585260-000000000-00000 · Cited by 91
A critical cysteine residue in monoacylglycerol lipase is targeted by a new class of isothiazolinone‐based enzyme inhibitors
King, A., Lodola, A., Carmi, C., Fu, J., Mor, M., & Piomelli, D. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00276.x · Cited by 91
Self-citation
Endocannabinoids in the Treatment of Mood Disorders: Evidence from Animal Models
Bambico, F. R., Duranti, A., Tontini, A., Tarzia, G., & Gobbi, G. (2009) · Current Pharmaceutical Design · doi:10.2174/138161209788168029 · Cited by 94
Self-citation
Brainstem Mechanisms of Pain Modulation: A within-Subjects 7T fMRI Study of Placebo Analgesic and Nocebo Hyperalgesic Responses
Crawford, L. S., Mills, E. P., Hanson, T., Macey, P. M., Glarin, R., Macefield, V. G., Keay, K. A., & Henderson, L. A. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0806-21.2021 · Cited by 92
High-Intensity Extended Swimming Exercise Reduces Pain-Related Behavior in Mice: Involvement of Endogenous Opioids and the Serotonergic System
Mazzardo‐Martins, L., Martins, D. F., Marcon, R., dos Santos, U. D., Speckhann, B., Gadotti, V. M., Sigwalt, A. R., Guglielmo, L. G. A., & Santos, A. R. S. (2010) · Journal of Pain · doi:10.1016/j.jpain.2010.03.015 · Cited by 90
A Decrease in Anandamide Signaling Contributes to the Maintenance of Cutaneous Mechanical Hyperalgesia in a Model of Bone Cancer Pain
Khasabova, I. A., Khasabov, S. G., Harding-Rose, C., Coicou, L. G., Seybold, B., Lindberg, A. E., Steevens, C. D., Simone, D. A., & Seybold, V. S. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2847-08.2008 · Cited by 90
Midbrain vlPAG inhibits rVLM cardiovascular sympathoexcitatory responses during electroacupuncture
Tjen‐A‐Looi, S. C., Li, P., & Longhurst, J. C. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01329.2005 · Cited by 90
Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats
Sciolino, N. R., Bortolato, M., Eisenstein, S. A., Fu, J., Oveisi, F., Hohmann, A. G., & Piomelli, D. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.04.007 · Cited by 89
Self-citation
Selective Monoacylglycerol Lipase Inhibitors: Antinociceptive versus Cannabimimetic Effects in Mice
Ignatowska-Jankowska, B. M., Wilkerson, J. L., Mustafa, M. A., Abdullah, R. A., Niphakis, M. J., Wiley, J. L., Cravatt, B. F., & Lichtman, A. H. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.222315 · Cited by 92
The CB1 Receptor as the Cornerstone of Exostasis
Piazza, P. V., Cota, D., & Marsicano, G. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.002 · Cited by 100
Endocannabinoid-mediated modulation of stress responses: Physiological and pathophysiological significance
Finn, D. P. (2009) · Immunobiology · doi:10.1016/j.imbio.2009.05.011 · Cited by 91
The Brainstem and Nociceptive Modulation
Heinricher, M. M., & Ingram, S. (2008) · Elsevier eBooks · doi:10.1016/b978-012370880-9.00183-3 · Cited by 87
Fatty acid amide hydrolase blockade attenuates the development of collagen-induced arthritis and related thermal hyperalgesia in mice
Kinsey, S. G., Naidu, P. S., Cravatt, B. F., Dudley, D. T., & Lichtman, A. H. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.06.022 · Cited by 87
The Role of the Brain's Endocannabinoid System in Pain and Its Modulation by Stress
Corcoran, L., Roche, M., & Finn, D. P. (2015) · International review of neurobiology · doi:10.1016/bs.irn.2015.10.003 · Cited by 90
Development and Pharmacological Characterization of Selective Blockers of 2-Arachidonoyl Glycerol Degradation with Efficacy in Rodent Models of Multiple Sclerosis and Pain
Brindisi, M., Maramai, S., Gemma, S., Brogi, S., Grillo, A., Di Cesare Mannelli, L., Gabellieri, E., Lamponi, S., Saponara, S., Gorelli, B., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01812 · Cited by 86
Self-citation
From endocannabinoid profiling to ‘endocannabinoid therapeutics’
Ligresti, A., Petrosino, S., & Marzo, V. D. (2009) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.04.615 · Cited by 88
Fatty Acid Amide Hydrolase: From Characterization to Therapeutics
Labar, G., & Michaux, C. (2007) · Chemistry & Biodiversity · doi:10.1002/cbdv.200790157 · Cited by 86
Chapter 5 The Endocannabinoid System as A Target for Novel Anxiolytic and Antidepressant Drugs
Gaetani, S., Dipasquale, P., Romano, A., Righetti, L., Cassano, T., Piomelli, D., & Cuomo, V. (2009) · International Review of Neurobiology · doi:10.1016/s0074-7742(09)85005-8 · Cited by 83
Self-citation
The effect of CB1 receptor antagonism in the right basolateral amygdala on conditioned fear and associated analgesia in rats
Roche, M., O'Connor, E., Diskin, C., & Finn, D. P. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05861.x · Cited by 83
Chemical approaches to therapeutically target the metabolism and signaling of the endocannabinoid 2-AG and eicosanoids
Kohnz, R. A., & Nomura, D. K. (2014) · Chemical Society Reviews · doi:10.1039/c4cs00047a · Cited by 86
Preservation of striatal cannabinoid CB1 receptor function correlates with the antianxiety effects of fatty acid amide hydrolase inhibition
Rossi, S., De Chiara, V., Musella, A., Sacchetti, L., Cantarella, C., Castelli, M., Cavasinni, F., Motta, C., Studer, V., Bernardi, G., et al. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.064196 · Cited by 82
Microglia produce and hydrolyze palmitoylethanolamide
Muccioli, G. G., & Stella, N. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.05.015 · Cited by 83
Δ9-Tetrahydrocannabinol protects hippocampal neurons from excitotoxicity
Gilbert, G. L., Kim, H. J., Waataja, J. J., & Thayer, S. A. (2006) · Brain Research · doi:10.1016/j.brainres.2006.03.011 · Cited by 81
Dissociation of Analgesic and Hormonal Responses to Forced Swim Stress Using Opioid Receptor Knockout Mice
Contet, C., Gavériaux‐Ruff, C., Matifas, A., Caradec, C., Champy, M., & Kieffer, B. L. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300934 · Cited by 81
Anandamide and neutrophil function in patients with fibromyalgia
Kaufmann, I., Schelling, G., Eisner, C. B., Richter, H. P., Krauseneck, T., Vogeser, M., Hauer, D., Campolongo, P., Choukèr, A., Beyer, A., et al. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.02.009 · Cited by 80
Cannabinoid hyperemesis syndrome: potential mechanisms for the benefit of capsaicin and hot water hydrotherapy in treatment
Richards, J. R., Lapoint, J. M., & Putze, G. B. (2017) · Clinical Toxicology · doi:10.1080/15563650.2017.1349910 · Cited by 80
Distribution of CB1 cannabinoid receptors and their relationship with mu-opioid receptors in the rat periaqueductal gray
Wilson-Poe, A. R., Morgan, M. M., Aicher, S. A., & Hegarty, D. M. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.03.038 · Cited by 79
Activation of Type 5 Metabotropic Glutamate Receptors and Diacylglycerol Lipase- Initiates 2-Arachidonoylglycerol Formation and Endocannabinoid-Mediated Analgesia
Gregg, L. C., Jung, K., Spradley, J. M., Nyilas, R., Suplita, R. L., Zimmer, A., Watanabe, M., Mackie, K., Katona, I., Piomelli, D., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0013-12.2012 · Cited by 79
Self-citation
Effects of exercise stress on the endocannabinoid system in humans under field conditions
Feuerecker, M., Hauer, D., Tóth, R., Demetz, F., Hölzl, J., Thiel, M., Kaufmann, I., Schelling, G., & Choukèr, A. (2011) · European Journal of Applied Physiology · doi:10.1007/s00421-011-2237-0 · Cited by 79

Authors: Hohmann, A. G., Suplita, R. L., Bolton, N. M., Neely, M. H., Fegley, D., Mangieri, R., Krey, J. F., Michael Walker, J., Holmes, P. V., Crystal, J. D., Duranti, A., Tontini, A., Mor, M., Tarzia, G., & Piomelli, D.
Affiliations: University of Georgia (US)
University of California, Irvine (US)
Brown University (US)
University of Urbino (IT)
University of Parma (IT)
Corresponding author: Hohmann, Andrea G.
Piomelli, Daniele
ORCID: Hohmann, Andrea G.
Bolton, Nathan M.
Mangieri, Regina
Krey, Jocelyn F.
Holmes, Philip V.
Crystal, Jonathon D.
Duranti, Andrea
Tontini, Andrea
Mor, Marco
Piomelli, Daniele
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2005-06
Volume: 435
Issue: 7045
Pages: 1108-1112
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature03658
OpenAlex: W2030777873
Cited by: 778
References: 30
Citations by year: 2026: 14 · 2025: 24 · 2024: 22 · 2023: 22 · 2022: 28 · 2021: 26 · 2020: 22 · 2019: 20 · 2018: 29 · 2017: 53 · 2016: 34 · 2015: 38 · 2014: 40 · 2013: 33 · 2012: 45
FWCI: 39.98
Type: journal article
Language: en
Open access: green
escholarship.org
Licence: cc-by
www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: stress-induced analgesia, endocannabinoid system, CB1 receptor, periaqueductal gray, 2-arachidonoylglycerol, anandamide, monoacylglycerol lipase, fatty acid amide hydrolase, opioid-independent analgesia, pain inhibition, stress-related disorders, therapeutic target
MeSH terms: Analgesia, Animals, Arachidonic Acids, Biological Transport, Biphenyl Compounds, Glycerides, Hydrolysis, Male, Mesencephalon, Monoacylglycerol Lipases, Stress, Physiological, Rats, Sprague-Dawley, Rats, Wistar, Receptor, Cannabinoid, CB1, Rats, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids, In Vitro Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

An endocannabinoid mechanism for stress-induced analgesia

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks