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State-dependent opioid control of pain
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“The high concentration of opioid receptors expressed in rACC (Vogt et al., 1993; Fields, 2004) has been hypothesized to relate to attentional mechanisms that can suppress pain processing (Petrovic et al., 2002), a suggestion that has received experimental support (Zubieta et al., 2005; Wager et al., 2007; Eippert et al., 2009).”
From Top-Down Dysregulation—From ADHD to Emotional Instability (2016) · cites this paper as Fields, 2004
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Molecular mechanisms of nociception
Julius, D., & Basbaum, A. I. (2001) · Nature · doi:10.1038/35093019 · Cited by 2,685 · cited 1×
“We now know a great deal about the molecular mechanisms of transduction and the relationship of the firing of these neurons to stimulus intensity and to the psychophysics of perceived pain intensit”
BackgroundTHE MECHANISM OF PLACEBO ANALGESIA
Levine, J., Gordon, N., & Fields, H. (1978) · The Lancet · doi:10.1016/s0140-6736(78)92762-9 · Cited by 1,094
Self-citationOrganization of endogenous opiate and nonopiate pain control systems
Watkins, L. R., & Mayer, D. J. (1982) · Science · doi:10.1126/science.6281891 · Cited by 791
Response expectancies in placebo analgesia and their clinical relevance
Pollo, A., Amanzio, M., Arslanian, A., Casadio, C., Maggi, G., & Benedetti, F. (2001) · Pain · doi:10.1016/s0304-3959(01)00296-2 · Cited by 442
Liebeskind, J. C., Guilbaud, G., Besson, J.-M., & Oliveras, J.-L. (1973) · Brain Research · doi:10.1016/0006-8993(73)90748-8 · Cited by 439
The role of conditioning and verbal expectancy in the placebo response
Voudouris, N. J., Peck, C. L., & Coleman, G. (1990) · Pain · doi:10.1016/0304-3959(90)90057-k · Cited by 369
Sucrose ingestion causes opioid analgesia.
Segato, F. N., Castro-Souza, C., Segato, E. N., Morato, S., & Coimbra, N. C. (1997) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x1997000800011 · Cited by 72
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Items 401–500 of 805
Refractory Migraine – A Review
Schulman, E. A. (2013) · Headache The Journal of Head and Face Pain · doi:10.1111/head.12047 · Cited by 31
“Patient expectations also affect their perception of pain.(114) Opioid receptors modulate neurons in a circuit that selectively controls nociceptive transmisTable 5.”
BackgroundKhasabov, S. G., Brink, T. S., Schupp, M., Noack, J., & Simone, D. A. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.08.029 · Cited by 26
Koutsikou, S., Parry, D. M., MacMillan, F., & Lumb, B. M. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05716.x · Cited by 24
“An emerging view (Fields, 2004; Mantyh & Hunt, 2004; Vanegas & Schaible, 2004) is that a subpopulation of supraspinally projecting lamina I neurones sets the level of descending control of deep dorsal horn neurones.”
BackgroundMånsson, K. N. T., Lasselin, J., Karshikoff, B., Axelsson, J., Engler, H., Schedlowski, M., Benson, S., Petrović, P., & Lekander, M. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.09.007 · Cited by 30
“…to descending control, as when the anterior cingulate inhibits incoming pain signals through connections with the brain-stem in placebo responses (Fields, 2004; Petrovic et al., 2002), or when interactions between the insula and anterior cingulate cortex together provide descending regulatory…”
Cooper, A. H., Hedden, N. S., Corder, G. F., Lamerand, S. R., Donahue, R. R., Morales‐Medina, J. C., Selan, L., Prasoon, P., & Taylor, B. K. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24846 · Cited by 29
“Also of interest is the rostral ventral medulla (RVM), a key regulator of chronic inflammatory nociception (Hurley and Hammond, 2001; Fields, 2004; Zhang and Hammond, 2010) that also mediates the manifestation of opiate withdrawal (Vera-Portocarrero et al.”
BackgroundA mu-Opioid Feedback Model of Human Social Behavior.
Meier, I., van Honk, J., Bos, P., & Terburg, D. (2020) · Neuroscience and Biobehavioral Reviews · doi:10.31234/osf.io/mhjyw · Cited by 25
“Opiates such as morphine and heroine do not only have pain relieving properties but can also generate strong appetitive motivational actions and do have addictive potential (Fields, 2004).”
BackgroundInfluentialFinan, P. H., Remeniuk, B., & Dunn, K. E. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.07.029 · Cited by 27
“Those behavioral changes are mediated by neurocircuitry within the mesolimbic reward system, which includes dopaminergic and opioidergic projections connecting subcortical regions involved in hedonic valuation, including the ventral tegmental area and striatum, to cortical regions involved in decision making and motiv…”
BackgroundInfluentialBiology of Neuropeptides: Orexinergic Involvement in Primary Headache Disorders
Holland, P. R. (2017) · Headache The Journal of Head and Face Pain · doi:10.1111/head.13078 · Cited by 26
“including the ventrolateral periaqueductal grey, rostral ventromedial medulla, and locus coeruleus.(53)”
BackgroundPleasure-Related Analgesia Activates Opioid-Insensitive Circuits
Kut, E., Candia, V., von Overbeck, J., Pok, J., Fink, D., & Folkers, G. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3736-10.2011 · Cited by 30
“Recent studies in animals and humans show that an opioidmediated descending pain system can inhibit or facilitate pain (Fields, 2004).”
BackgroundNetwork targets for therapeutic brain stimulation: towards personalized therapy for pain
Motzkin, J. C., Kanungo, I., D’Esposito, M., & Shirvalkar, P. R. (2023) · Frontiers in Pain Research · doi:10.3389/fpain.2023.1156108 · Cited by 25
“A substantial body of preclinical evidence convincingly shows that PAG stimulation is antinociceptive (41, 83, 143, 144, 149, 152).”
BackgroundRidder, D. D., Friston, K. J., Sedley, W., & Vanneste, S. (2023) · Brain Communications · doi:10.1093/braincomms/fcad132 · Cited by 25
Fanton, S., Sandström, A., Tour, J., Kadetoff, D., Schalling, M., Jensen, K. B., Sitnikov, R., Ellerbrock, I., & Kosek, E. (2021) · Pain · doi:10.1097/j.pain.0000000000002309 · Cited by 27
Cetas, J. S., Lee, D. R., Alkayed, N. J., Wang, R. K., Iliff, J. J., & Heinricher, M. M. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.06.031 · Cited by 25
“This is generally considered beneficial, and the inhibitory output from the RVM is suppressed under these conditions (Porreca et al., 2002; Fields, 2004; Heinricher et al., 2009).”
BackgroundSanoja, R., Vanegas, H., & Tortorici, V. (2008) · Journal of Pain · doi:10.1016/j.jpain.2008.01.332 · Cited by 24
Tortorici, V., Aponte, Y., Acevedo, H., Nogueira, L., & Vanegas, H. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06678.x · Cited by 23
“To a great extent, the analgesic effect of opiates is due to their action upon the periaqueductal gray matter (PAG; Fields, 2004), and this action is also critical for the development of tolerance (Lane et al., 2005).”
BackgroundInfluentialLee, M. T., Peng, W., Wu, C., Kan, H., Wang, D., Teng, Y., & Ho, Y. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03439-z · Cited by 24
Tinnermann, A., Sprenger, C., & Büchel, C. (2022) · eLife · doi:10.7554/elife.74293 · Cited by 31
“On the one hand, early work on descending pain modulation has shown that cells that originate in the brainstem and that can inhibit and facilitate spinal nociceptive processing are either directly connected to ascending projection neurons or through one interneuron (Fields, 2004).”
BackgroundInfluentialChronic pain precedes disrupted eating behavior in low-back pain patients
Lin, Y., de Araújo, I. E., Stanley, G., Small, D. M., & Geha, P. (2022) · PLoS ONE · doi:10.1371/journal.pone.0263527 · Cited by 25
Xu, H., Chen, Y., Yin, T., Zhang, Y., Zhao, T., Wang, M., Fan, L.-H., Zheng, Y., & Guo, C. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13803 · Cited by 23
Tinnitus and Brain Stimulation
Ridder, D. D., Adhia, D. B., & Langguth, B. (2021) · Current topics in behavioral neurosciences · doi:10.1007/7854_2021_219 · Cited by 35
Potential Activity of Medicinal Plants as Pain Modulators: A Review
Silva-Correa, C. R., Campos-Reyna, J. L., Torre, V. E. V.-L., Calderón-Peña, A. A., González-Blas, M. V., Aspajo-Villalaz, C. L., Cruzado-Razco, J. L., Sagástegui-Guarniz, W. A., Guerrero-Espino, L. M., & Hilario-Vargas, J. S. (2021) · Pharmacognosy Journal · doi:10.5530/pj.2021.13.35 · Cited by 20
Hughes, P. A., Costello, S. P., Bryant, R. V., & Andrews, J. M. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00442.2015 · Cited by 22
“While there is ample evidence that opioids alter immune function, in vivo opioid dosing affects CNS and HPA axis signaling, and, therefore, altered immune function may occur indirectly (5, 36).”
BackgroundAira, Z., Barrenetxea, T., Buesa, I., del Caño, G. G., & Azkue, J. J. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2469-15.2016 · Cited by 23
“The endogenous peptide met-enkephalin is abundantly expressed in the spinal dorsal horn (Todd and Spike, 1992; Mar- vizón et al., 2009) and presents high affinity for MOR (Delfs et al., 1994; Raynor et al., 1994; Fields, 2004).”
BackgroundInfluentialRole of endogenous opioids in the control of gastric sensorimotor function
Geeraerts, B., Mimidis, K., Oudenhove, L. V., Vos, R., Karamanolis, G. P., & Tack, J. F. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01144.x · Cited by 23
Kavaliers, M., Devidze, N., Choleris, E., Fudge, M. A., Gustafsson, J., Korach, K., Pfaff, D., & Ogawa, S. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.02.003 · Cited by 23
“This stress-induced analgesia reflects a motivational shift that facilitates the expression of various active and passive defensive behavioral responses (Fields, 2004), thereby reducing the risk of predation.”
BackgroundPlacebo: From Pain and Analgesia to Preferences and Products
Borsook, D., & Becerra, L. R. (2005) · Journal of Marketing Research · doi:10.1509/jmkr.2005.42.4.394 · Cited by 21
“…fully elucidated, though pain and analgesia have provided the most compelling and mechanistic insights into the phenomenon (Amanzio and Benedetti 1999; Beecher 1955; Benedetti et al. 2003; Fields 1981; Gracely et al. 1983; Levine, Gordon, and Fields 1978; Levine et al. 1979; Petrovic et al. 2002).”
BackgroundJohansson, E., Xiong, H.-Y., Polli, A., Coppieters, I., & Nijs, J. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13061645 · Cited by 23
“Given the established role of the PAG in top-down endogenous pain modulation [93,94], the authors suggested that people with chronic pain who exhibit an altered functional behaviour of the dorsal vmPFC might be more likely to spontaneously ruminate about pain, which in turn may disrupt the…”
BackgroundEllerbrock, I., Sandström, A., Tour, J., Fanton, S., Kadetoff, D., Schalling, M., Jensen, K. B., Sitnikov, R., & Kosek, E. (2021) · Molecular Brain · doi:10.1186/s13041-021-00789-4 · Cited by 25
“5-HT is involved in controlling nociceptive transmission, where it can exert inhibitory or facilitatory effects [10, 33], and in common FM comorbidities, e.”
BackgroundSilva, J. T. D., Tricou, C., Zhang, Y., Tofighbakhsh, A., Seminowicz, D. A., & Ro, J. Y. (2021) · Aging Cell · doi:10.1111/acel.13292 · Cited by 25
“We selected PAG as the region of interest (ROI) based upon prior literature showing its involvement in descending pain inhibition (Fields, 2004), which is also modulated by sex and age (Da Silva et al., 2018, 2020).”
BackgroundMethodRoute of placebo administration: Robust placebo effects in laboratory and clinical settings
Liu, T. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.09.018 · Cited by 25
“The DPMS within the PAG functions in a manner depending on motivational state (Fields, 2004); however, changes in its functional state may to some extent lag behind changes in motivational state.”
InfluentialMcGovern, A. E., Ajayi, I. E., Farrell, M. J., & Mazzone, S. B. (2017) · Journal of Thoracic Disease · doi:10.21037/jtd.2017.08.119 · Cited by 25
“The capacity to facilitate or inhibit sensory processing presumably allows behavioral responses to noxious stimulation to be matched with competing demands (27).”
BackgroundVuilleumier, P. H., Arguissain, F. G., Manresa, J. A. B., Neziri, A. Y., Nirkko, A. C., Andersen, O. K., Arendt‐Nielsen, L., & Curatolo, M. (2017) · Journal of Pain · doi:10.1016/j.jpain.2017.05.008 · Cited by 21
The Pain System in Oesophageal Disorders: Mechanisms, Clinical Characteristics, and Treatment
Lottrup, C., Olesen, S. S., & Drewes, A. M. (2011) · Gastroenterology Research and Practice · doi:10.1155/2011/910420 · Cited by 19
“In particular, connections between these sites, commonly referred to as the descending modulatory pain pathways, play a central role [34, 35].”
BackgroundTolerance to Non-Opioid Analgesics is Opioid Sensitive in the Nucleus Raphe Magnus
Tsagareli, M. G., Nozadze, I., Tsiklauri, N., & Gurtskaia, G. (2011) · Frontiers in Neuroscience · doi:10.3389/fnins.2011.00092 · Cited by 20
“In naive rats, microinjection of morphine and dipyrone into the PAG decrease the activity of pain-facilitating “on-cells” and increase the activity of pain inhibiting “off-cells” thus giving rise to antinociception (Tortorici et al., 2001, 2009; Fields, 2004).”
Anterior Cingulate Implant for Obsessive-Compulsive Disorder
Ridder, D. D., Leong, S. L., Manning, P. J., Vanneste, S., & Glue, P. (2016) · World Neurosurgery · doi:10.1016/j.wneu.2016.10.046 · Cited by 22
Baker, A. K., & Garland, E. L. (2019) · Experimental and Clinical Psychopharmacology · doi:10.1037/pha0000225 · Cited by 21
“…(Volkow & McLellan, 2016) and subsequent reward dysregulation by way of two conditioned responses, wherein pain relief and opioid-induced euphoria become associated with opioid cues via negative and positive reinforcement, respectively (Fields, 2004; Shippenberg, Bals-Kubik, & Herz, 1993).”
Placebo and nocebo effects: from observation to harnessing and clinical application
Tu, Y., Zhang, L., & Kong, J. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02293-2 · Cited by 34
Acupuncture Enhances Dorsal Raphe Functional Connectivity in Knee Osteoarthritis With Chronic Pain
Gao, N., Shi, H., Hu, S., Zha, B., Yuan, A., Shu, J., Fan, Y., Bai, J., Xie, H., Cui, J., et al. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2021.813723 · Cited by 20
“Periaqueductal gray (PAG) plays a central role in the descending modulation of pain (26).”
BackgroundMoon, H. C., & Park, Y. S. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-021-01898-4 · Cited by 21
Lee, S., Choi, B. Y., Koo, J., Ridder, D. D., & Song, J. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.596647 · Cited by 25
“In previous pain studies, the degree of improvement after spinal cord stimulation depended on activation of the pgACC (Moens et al., 2012), which is a part of the descending pain inhibitory pathway (Fields, 2004; Kong et al., 2010), the somatosensory analog of the noise canceling system.”
BackgroundAndrade, P., Heiden, P., Visser-Vandewalle, V. E. R. M., & Matis, G. (2020) · Neuromodulation Technology at the Neural Interface · doi:10.1111/ner.13278 · Cited by 22
“modulate the cholinergic system and decrease pain intensity (5).”
BackgroundZamorano, A. M., Montoya, P., Cifré, I., Vuust, P., Riquelme, I., & Kleber, B. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.116103 · Cited by 20
“, 2016), motivational aspects of playing an instrument may engage protective factors that can help musicians to cope with pain (Fields, 2004; Tracey and Mantyh, 2007).”
BackgroundInfluentialThe Role of miR-539 in the Anterior Cingulate Cortex in Chronic Neuropathic Pain
Ding, M., Shen, W., & Hu, Y. (2017) · Pain Medicine · doi:10.1093/pm/pnx004 · Cited by 21
Volume gain of periaqueductal gray in medication-overuse headache
Chen, Z., Chen, X., Liu, M., Liu, S., Ma, L., & Yu, S. (2017) · The Journal of Headache and Pain · doi:10.1186/s10194-016-0715-9 · Cited by 21
“PAG is a substantial descending pain modulatory center, which exerts a dual control (including inhibition and facilitation) on nociceptive transmission in the dorsal horn and trigeminal nucleus [10], and the modulatory mechanism was exerted by descending PAG-RVM (rostral ventromedial medulla) pathway contributing to c…”
BackgroundPourbasheer, E., Beheshti, A., Khajehsharifi, H., Ganjali, M., & Norouzi, P. (2013) · Medicinal Chemistry Research · doi:10.1007/s00044-012-0412-4 · Cited by 21
“Optimal training and test sets were generated by k-means cluster analysis (Everitt, 1993).”
Khasabov, S. G., & Simone, D. A. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.06.057 · Cited by 23
“At the neuronal level, morphine inhibits ON neurons and blocks activity of interneurons that tonically decrease the excitability of OFF cells, causing disinhibition and activation of OFF cells (see review, Fields, 2004).”
Boxwell, A. J., Yanagawa, Y., Travers, S. P., & Travers, J. B. (2013) · Journal of Neurophysiology · doi:10.1152/jn.00711.2012 · Cited by 23
Decision Points: The Factors Influencing the Decision to Feed in the Medicinal Leech
Gaudry, Q., & Kristan, W. B. (2012) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00101 · Cited by 22
“…responsible for pain suppression is expressed at every known supraspinal component of the pain modulating pathway, including the insular cortex, amygdala, hypothalamus, periaqueductal gray, dorsolateral pontine tegmentum, rostral ventromedial medulla, and the spinal cord dorsal horn (Fields, 2004).”
BackgroundMarie, N., Aguila, B., Hasbi, A., Davis, A., Jauzac, P., & Allouche, S. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2008.02.010 · Cited by 21
Molecular modeling and 3D-QSAR studies of indolomorphinan derivatives as kappa opioid antagonists.
Li, W., Tang, Y., Zheng, Y.-L., & Qiu, Z. (2006) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2005.08.052 · Cited by 21
Descending Pain Modulation in Fibromyalgia: A Short Review of Mechanisms and Biomarkers
Carneiro, B. D., Torres, S., Costa‐Pereira, J. T., Pozza, D. H., & Tavares, I. (2025) · Diagnostics · doi:10.3390/diagnostics15212702 · Cited by 20
“Descending pain modulation involves complex neural circuits spanning cortical, subcortical, and brainstem regions, including the prefrontal cortex (PFC), anterior cingulate cortex (ACC), periaqueductal gray (PAG), and rostral ventromedial medulla (RVM) [24].”
Kim, Y. E., Kim, M. K., Suh, S., & Kim, J. H. (2021) · BMC Neurology · doi:10.1186/s12883-021-02374-7 · Cited by 26
Wang, W., Zhong, X., Li, Y., Guo, R.-X., Du, S., Wen, L., Ying, Y.-L., Yang, T., & Wei, X.-H. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14650 · Cited by 20
“The rostral ventromedial medulla (RVM), consisting of the nucleus raphe magnus, nucleus reticularis gigantocellularis, and nucleus gigantocellularis pars alpha (Gi), has been implicated as a key brainstem structure that exerts powerful descending modulation of pain transmission through direct projections to the spinal…”
BackgroundImaging clinically relevant pain states using arterial spin labeling
Loggia, M. L., Segerdahl, A. R., Howard, M. A., & Tracey, I. (2019) · PAIN Reports · doi:10.1097/pr9.0000000000000750 · Cited by 23
“Importantly, unlike other experimentally induced models, the experience is due to trauma to soft tissue and bone, resulting in prolonged and inescapable pain; qualities likely to engage endogenous pain control systems.(23) Accordingly, the acute”
BackgroundLourença, F., Carvalhosa, A. R., Ferreira-Gomes, J., Reguenga, C., & Castro-Lopes, J. (2008) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2008.05.004 · Cited by 20
Curley, J. P. (2011) · Behavioral Neuroscience · doi:10.1037/a0022939 · Cited by 19
A diencephalic circuit in rats for opioid analgesia but not positive reinforcement
Waung, M. W., Maanum, K. A., Cirino, T. J., Driscoll, J. R., OʼBrien, C., Bryant, S., Mansourian, K. A., Morales, M., Barker, D. J., & Margolis, E. B. (2022) · Nature Communications · doi:10.1038/s41467-022-28332-6 · Cited by 19
Why we need more research into the placebo response in psychiatry
Huneke, N. T. M., van der Wee, N. J. A., Garner, M. J., & Baldwin, D. S. (2020) · Psychological Medicine · doi:10.1017/s0033291720003633 · Cited by 26
“This region is also known to be important in placebo analgesia (Atlas & Wager, 2014) and is a key node in the endogenous opioid system (Fields, 2004).”
BackgroundShu, R., Zhang, L., Zhang, H., Li, Y., Wang, C., Su, L., Zhao, H., & Wang, G. (2020) · Journal of Pain · doi:10.1016/j.jpain.2020.03.007 · Cited by 20
Developmental neurobiology as a guide for pharmacological management of pain in neonates
van den Hoogen, N. J., de Kort, A. R., Allegaert, K., Joosten, E. A. J., Simons, S. H. P., Tibboel, D., & van den Bosch, G. E. (2019) · Seminars in Fetal and Neonatal Medicine · doi:10.1016/j.siny.2019.05.004 · Cited by 22
“Endogenous opioids β-endorphin and enkephalins (met- and leu-enkephalin) or analgesic drugs such as morphine or fentanyl can produce powerful analgesia by inhibiting the firing of nociceptive neurons in the dorsal horn of the spinal cord [31].”
BackgroundInfluentialAhmed, S., Plazier, M., Ost, J., Stassijns, G., Deleye, S., Ceyssens, S. K., Dupont, P. J., Stroobants, S. G., Staelens, S. G., Ridder, D. D., et al. (2018) · BMC Neurology · doi:10.1186/s12883-018-1190-5 · Cited by 21
Kreitz, S., Alonso, B. D. C., Uder, M., & Heß, A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00334 · Cited by 20
“within the cortex by inhibitory connections and thalamo-cortical loops (Robinson, 2017) or even to sub-cerebral structures like the spinal cord in pain conditions (Fields, 2004).”
BackgroundPain vulnerability and DNA methyltransferase 3a involved in the affective dimension of chronic pain
Wang, W., Li, C., Cai, Y., & Pan, Z. Z. (2017) · Molecular Pain · doi:10.1177/1744806917726713 · Cited by 23
Block, L., Forshammar, J., Westerlund, A., Björklund, U., Lundborg, C. N., Biber, B., & Hansson, E. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2011.12.058 · Cited by 17
“The classical opioid system is best known for its effects on nociception (Fields, 2004),”
BackgroundKlinische Bedeutung des Placeboeffektes
Oeltjenbruns, J., & Schäfer, M. (2008) · Der Anaesthesist · doi:10.1007/s00101-008-1370-6 · Cited by 18
Somatotopic organization of brainstem analgesic circuitry
Crawford, L. S., Mendoza, F. A. T., Robertson, R. V., Meylakh, N., Macey, P. M., Bannister, K., Wager, T. D., Macefield, V. G., Keay, K. A., & Henderson, L. A. (2025) · Science · doi:10.1126/science.adu8846 · Cited by 20
Secci, M. E., Kelley, L. K., Avegno, E. M., Holmgren, E. B., Chen, L., Rein, S., Engi, S. A., Quinlan, V., Wilson, L., Gilpin, N. W., et al. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.09.006 · Cited by 22
Current and emerging methods for probing neuropeptide transmission
Qian, T., Wang, H., Xia, X., & Li, Y. (2023) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2023.102751 · Cited by 21
“…energy homeostasis and food intake in rodents [5]; gastrin-releasing peptide (GRP) and substance P, produced by sensory neurons in the spinal cord, are thought to code for itch and pain, respectively [6,7]; and endogenous opioid peptides have been implicated in analgesia and substance abuse [8].”
Huneke, N. T. M., Aslan, I. H., Fagan, H. A., Phillips, N., Tanna, R., Cortese, S., Garner, M. J., & Baldwin, D. S. (2022) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyac009 · Cited by 24
“The endogenous opioid system is important in placebo analgesia (Fields, 2004; Benedetti et al., 2011).”
BackgroundYücel, N. T., Kandemir, Ü., Özkay, Ü. D., & Can, Ö. D. (2021) · Molecules · doi:10.3390/molecules26113242 · Cited by 17
“In addition to the noradrenergic system, serotonergic system is known to interact with the opioid-mediated pain modulatory circuit [47].”
BackgroundDistinct neural networks subserve placebo analgesia and nocebo hyperalgesia
Fu, J., Wu, S., Liu, C., Camilleri, J. A., Eickhoff, S. B., & Yu, R. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.117833 · Cited by 30
“Studies also found that the endogenous opioid system is essential for both placebo and nocebo effects (Amanzio and Benedetti, 1999; Benedetti et al., 1999; Fields, 2004; Petrovic et al., 2002).”
InfluentialCosta, A. R., Carvalho, P., Flik, G., Wilson, S. P., Reguenga, C., Martins, I., & Tavares, I. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00287 · Cited by 21
“Opioids are paramount in the control of descending pain modulatory areas (Fields, 2004; Ossipov et al., 2010), but the effects of chronic neuropathic pain on the opioidergic modulation of pain control centers of the brain remain understudied.”
BackgroundBaptista‐de‐Souza, D., Pelarin, V., Canto‐de‐Souza, L., Nunes‐de‐Souza, R. L., & Canto‐de‐Souza, A. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.07.027 · Cited by 17
“Furthermore, it has to be highlighted that PAG controls the nociceptive transmission through connections with rostral ventromedial medulla (RVM) wherein modulates ON- and OFF-cells (responsible, respectively, for facilitating and inhibiting pain at spinal cord level) (Fields, 2004; Palazzo et al., 2008).”
Yokota, E., Koyanagi, Y., Yamamoto, K., Oi, Y., Koshikawa, N., & Kobayashi, M. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.10.004 · Cited by 20
“Minor role of KOR in GABAergic synaptic transmission KOR agonists also have antinociceptive effects (Fields, 2004).”
Tao, W., Chen, Q., Wang, L., Zhou, W., Wang, Y., & Zhang, Z. (2015) · Molecular Pharmacology · doi:10.1124/mol.115.098186 · Cited by 20
Pain Relativity in Motor Control
Kurniawan, I. T., Seymour, B., Vlaev, I., Trommershäuser, J., Dolan, R. J., & Nick Chater, A. (2010) · Psychological Science · doi:10.1177/0956797610370160 · Cited by 18
“As the body’s primary aversive stimulus, pain signals imminent or actual physical harm, evokes a feeling of unpleasantness, and constitutes a potent signal that helps to shape future behavior toward minimizing injury (Craig, 2003; Fields, 2004).”
BackgroundInvolvement of the κ-opioid receptor in nitrous oxide-induced analgesia in mice
Koyama, T., & Fukuda, K. (2010) · Journal of Anesthesia · doi:10.1007/s00540-010-0886-5 · Cited by 18
“N2O-induced KOP activation may suggest a negative interaction between N2O and opioid agonists in clinical settings, because an opposing interaction between KOP and MOP has been reported [19, 20].”
BackgroundOpioid and placebo analgesia share the same network
Petrović, P. (2005) · Seminars in Pain Medicine · doi:10.1016/j.spmd.2005.02.005 · Cited by 19
Tour, J., Sandström, A., Kadetoff, D., Schalling, M., & Kosek, E. (2022) · PLoS ONE · doi:10.1371/journal.pone.0277427 · Cited by 18
“The opioid system interacts with the serotonergic pain regulatory system in an antagonistic, time- and state dependent way [59].”
BackgroundCooper, A. H., Hedden, N. S., Prasoon, P., Qi, Y., & Taylor, B. K. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.2038-21.2022 · Cited by 22
“Pathways from the 79 RVM can be inhibitory or excitatory, and their net impact determines the modulation of spinal nociceptive 80 signaling (Porreca et al., 2002; Fields, 2004; Chen and Heinricher, 2019).”
BackgroundLlorca-Torralba, M., Pilar-Cuéllar, F., Borges, G., Micó, J. A., & Berrocoso, E. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.109857 · Cited by 19
Opioid and nondopamine reward circuitry and state‐dependent mechanisms
Fujita, M., Ide, S., & Ikeda, K. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13605 · Cited by 15
Dopaminergic mechanisms in periaqueductal gray-mediated antinociception
Tobaldini, G., Reis, R. A., Sardi, N. F., Lazzarim, M. K., Tomim, D. H., Lima, M. M. S., & Fischer, L. (2017) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000346 · Cited by 26
“modulation pathways from RVM (Millan, 2002; Fields, 2004), is not recruited by selective dopaminergic D2-like activity.”
BackgroundMethodInfluentialTao, W., Zhou, W., Wang, Y., Sun, T., Wang, H., Zhang, Z., & Jin, Y. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.09.015 · Cited by 18
Allostasis in health and food addiction
Ridder, D. D., Manning, P. J., Leong, S. L., Ross, S., & Vanneste, S. (2016) · Scientific Reports · doi:10.1038/srep37126 · Cited by 18
Vigil, J. (2011) · Pain Research and Management · doi:10.1155/2011/280531 · Cited by 17
“In addition to promoting self-awareness (eg, to attend to and to protect an injured body part) and learning (eg, to avoid dangerous stimuli [11,12]), pain suffering may have evolved, in part, to be facultatively available to sensory awareness so as to express pain behaviours to selective relationship partners.”
BackgroundCorticofugal outputs facilitate acute, but inhibit chronic pain in rats
Wang, N., Wang, J., & Luo, F. (2009) · Pain · doi:10.1016/j.pain.2008.12.016 · Cited by 17
“Although many studies have indicated that the central network mediating chronic pain predominantly involves facilitatory mechanism in the spinothalamic pathways [18,20,44,65], Crick and Koch have pointed out that the corticothalamic circuits never form strong directed loops, because too strong excitatory loop would th…”
BackgroundGuedes, A., Papich, M., Rudé, E. P., & Rider, M. (2007) · Journal of Veterinary Pharmacology and Therapeutics · doi:10.1111/j.1365-2885.2007.00849.x · Cited by 17
The total challenge of cancer pain in supportive and palliative care.
Ahmedzai, S., & Boland, J. (2007) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0b013e328151c401 · Cited by 17
Chen, X., Spaeth, R. B., Freeman, S. G., Scarborough, D. M., Hashmi, J. A., Wey, H., Egorova, N., Vangel, M. G., Mao, J., Wasan, A. D., et al. (2015) · Molecular Pain · doi:10.1186/s12990-015-0071-9 · Cited by 76
Drosophila pain sensitization and modulation unveiled by a novel pain model and analgesic drugs
Jang, W., Oh, M., Cho, E.-H., Baek, M., & Kim, C. (2023) · PLoS ONE · doi:10.1371/journal.pone.0281874 · Cited by 19
Chen, Y., Kang, Y., Luo, S., Liu, S., Wang, B., Gong, Z., Huang, Y., Wang, H., Zhan, S., & Tan, W. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.925698 · Cited by 18
“ON and OFF cells within the RVM were activated by the onset and offset of noxious stimulation (Fields, 2004).”
BackgroundMemik, N. Ç., Hunç, F., Kalayci, S., DEMİR, N., Şentürk, E., Gündoğdu, Ö. Y., & Dillioğlugil, M. Ö. (2022) · Archives of Suicide Research · doi:10.1080/13811118.2022.2066494 · Cited by 16
“The relationship between EOS and pain perception has been theorized, that EOS modulate sensitivity to pain, increase response to the sudden stress, inhibit stress response, create stress analgesia, and cause pain not to be perceived immediately at the beginning of the event (Claes, Vandereycken, & Vertommen, 2006; Der…”
BackgroundWitjes, B., Ottenheym, L. A., Huygen, F., & de Vos, C. D. (2022) · Neuromodulation (Malden, Mass.) · doi:10.1016/j.neurom.2022.04.036 · Cited by 16
Observation of others’ painful heat stimulation involves responses in the spinal cord
Tinnermann, A., Büchel, C., & Haaker, J. (2021) · Science Advances · doi:10.1126/sciadv.abe8444 · Cited by 12
Predictive mechanisms linking brain opioids to chronic pain vulnerability and resilience
Jones, A. K. P., & Brown, C. A. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13840 · Cited by 17
“(D) The cortical and subcortical projections all converge onto the PAG-RVM-spinal cord system which either inhibits or facilitates nociception (Fields, 2004).”
BackgroundImbe, H., & Kimura, A. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.007 · Cited by 15
Miranda-Páez, A., Zamudio, S., Vázquez-León, P., Campos-Rodríguez, C., & Juan, E. R. (2016) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2016.01.002 · Cited by 17
“RVM off-cells are activated by local infusion of either morphine selective ligands or the GABAA receptor antagonist bicuculline (Heinricher and Tortorici, 1994; Heinricher et al., 1994), and this leads to an anti-nociceptive effect (Fields, 2004).”
InfluentialLü, Y.-F., Wang, Y., He, Y. Z., Zhang, F.-K., He, T., Wang, R., Chen, X.-F., Yang, F., Gong, K., & Chen, J. (2013) · Neuroscience Bulletin · doi:10.1007/s12264-013-1344-9 · Cited by 18
“has an endogenous modulatory system to stop pain under certain conditions([2-4]).”
Inhibition of Activity of GABA Transporter GAT1 by δ -Opioid Receptor
Pu, L., Xu, N., Xia, P., Gu, Q., Ren, S., Fucke, T., Pei, G., & Schwarz, W. (2012) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2012/818451 · Cited by 16
“Activation of opioid receptors has also been shown to regulate pain sensation, and the role of δOR in pain modulation is intriguing [25, 26], Importantly, δOR has been found to be increasingly targeted to the plasma membrane in the spinal cord dorsal horn in inflammation [27].”
Background
Metadata
- Authors
- Fields, H.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Fields, Howard
- ORCID
- Fields, Howard
- Venue
- Nature Reviews Neuroscience
- Published
- 2004-07
- Volume
- 5
- Issue
- 7
- Pages
- 565-575
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2030751218
- Cited by
- 946
- References
- 0
- Citations by year
- 2026: 46 · 2025: 43 · 2024: 36 · 2023: 42 · 2022: 54 · 2021: 52 · 2020: 38 · 2019: 43 · 2018: 49 · 2017: 66 · 2016: 45 · 2015: 39 · 2014: 48 · 2013: 47 · 2012: 56
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- opioid analgesia, mu-opioid receptor, delta opioid receptor, kappa opioid receptor, motivational states, aversive motivation, appetitive motivation, pain transmission, pain modulation, opioid use disorder, choice behavior
- MeSH terms
- Analgesics, Opioid, Animals, Behavior, Animal, Humans, Medulla Oblongata, Models, Neurological, Motivation, Opioid-Related Disorders, Neural Pathways, Neurons, Nociceptors, Pain, Receptors, Opioid, Reinforcement, Psychology, Serotonin, Synapses, Neural Networks, Computer
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