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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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Male risk taking, female odors, and the role of estrogen receptors
Kavaliers, M., Clipperton‐Allen, A. E., Cragg, C. L., Gustafsson, J.-Α., Korach, K. S., Muglia, L. J., & Choleris, E. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.03.017 · Cited by 21
“Rather, it is associated with stress-induced activation of opioid and, or non-opioid neurochemical mechanism [48,56] that reflects a motivational shift that facilitates the expression of various active and passive defensive behavioral responses [57], thereby reducing the risk of predation.”
Interaction and regulatory functions of μ- and δ-opioid receptors in nociceptive afferent neurons
Zhang, X., & Bao, L. (2012) · Neuroscience Bulletin · doi:10.1007/s12264-012-1206-x · Cited by 16
“[82] Fields H.”
Neural basis of transcutaneous electrical nerve stimulation for neuropathic pain relief
Liu, S., Long, S., Li, F., Yang, H., Pu, S., Du, D., Luo, X., Zhang, Y., & Han, Q. (2025) · Neuron · doi:10.1016/j.neuron.2025.08.010 · Cited by 16
Amo, R., Uchida, N., & Watabe‐Uchida, M. (2024) · Neuron · doi:10.1016/j.neuron.2023.12.019 · Cited by 23
“Although opioids affect multiple sites in pain pathways, as well as reward pathways, in the brain, 65–67 we found that buprenorphine, a partial m -opioid agonist/ k -opioid antagonist, dramatically decreased inhibitory responses to an aversive stimulus in dopamine neurons but did not affect their…”
Mathew, J., Adhia, D. B., Smith, M. L., Ridder, D. D., & Mani, R. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.899772 · Cited by 19
“Therefore, the objectives of the study were: (1) to assess the feasibility, safety, and acceptability of ISF-NF training in individuals with KOA; (2) to descriptively report the variability of change in the clinical and experimental pain outcomes in people with KOA following NF training; (3) to descriptively explore t…”
BackgroundInfluentialGluA1 in central amygdala increases pain but inhibits opioid withdrawal-induced aversion
Cai, Y.-Q., Hou, Y.-Y., & Pan, Z. Z. (2020) · Molecular Pain · doi:10.1177/1744806920911543 · Cited by 15
“Pain is known as an aversive stimulus and is often associated with negative emotion such as aversion and anxiety.(28,30,31) We have shown that CFA-induced persistent pain causes strong and long-lasting (> a month) place aversion in rats.”
BackgroundAre neural pathways processing airway inputs sensitized in patients with cough hypersensitivity?
Farrell, M. J., & Mazzone, S. B. (2019) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2019.101806 · Cited by 16
Mediation of Movement-Induced Breakthrough Cancer Pain by IB4-Binding Nociceptors in Rats
Havelin, J., Imbert, I., Sukhtankar, D., Remeniuk, B., Pelletier, I., Gentry, J., Okun, A., Tiutan, T., Porreca, F., & King, T. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1212-16.2017 · Cited by 15
Opioidergic tone and pain susceptibility: interactions between reward systems and opioid receptors
Borsook, D. (2017) · Pain · doi:10.1097/j.pain.0000000000000726 · Cited by 15
Nakamura, T., Tomida, M., Yamamoto, T., Ando, H., Takamata, T., Kondo, E., Kurasawa, I., & Asanuma, N. (2013) · The Open Dentistry Journal · doi:10.2174/1874210601307010027 · Cited by 14
“MOR activation of the descending pain-control circuits depends on an opioid related to GABAergic neurotransmission in the PAG [25, 26].”
BackgroundTsagareli, M. G., Tsiklauri, N., Nozadze, I., & Gurtskaia, G. (2012) · PubMed Central · doi:10.3969/j.issn.1673-5374.2012.13.010 · Cited by 18
Yoshikawa, M., Ito, K., Maeda, M., Akahori, K., Takahashi, S., Jin, X. L., Matsuda, M., Suzuki, T., Oka, T., Kobayashi, H., et al. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.02.042 · Cited by 15
Shang, G.-W., Liu, D., Yan, L.-H., Cui, X.-Y., Zhang, K.-P., Qi, C., & Chen, J. (2006) · Pharmacology, Biochemistry and Behavior · doi:10.1016/j.pbb.2006.09.016 · Cited by 15
Opioidergic activation of the descending pain inhibitory system underlies placebo analgesia
Neyama, H., Wu, Y., Nakaya, Y., Kato, S., Shimizu, T., Tahara, T., Shigeta, M., Inoue, M., Miyamichi, K., Matsushita, N., et al. (2025) · Science Advances · doi:10.1126/sciadv.adp8494 · Cited by 21
Adhia, D. B., Mani, R., Turner, P. R., Vanneste, S., & Ridder, D. D. (2022) · Brain Sciences · doi:10.3390/brainsci12111514 · Cited by 15
“The two ascending pain pathways are balanced by a descending pain inhibitory path‐ way [33,34], involving the pgACC, the periaqueductal gray, the para‐hippocampal area, the hypothalamus, and the rostral ventromedial brainstem [33–35].”
BackgroundInvolvement of the Dorsal Vagal Complex in Alcohol-Related Behaviors
Keller, B. N., Hajnal, A. S., Browning, K. N., Arnold, A. C., & Silberman, Y. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.801825 · Cited by 16
“…1993; Rasmussen et al., 2002). β-endorphin, a mediator of endogenous analgesia, the stress response, reward, cardiorespiratory regulation, and food intake, is also shown to modulate alcohol intake behavior (Lewis et al., 1987; Appleyard et al., 2003; Fields, 2004; Butler and Finn, 2009).”
BackgroundElina, K. C., Oh, B. H., Islam, J., Kim, S., & Park, Y. S. (2021) · The Journal of Headache and Pain · doi:10.1186/s10194-021-01257-z · Cited by 15
“Via projections to the RVM, the vlPAG modulates spinal cord nociceptive transmission, establishing the PAG-RVM-spinal descending pain inhibitory network [56].”
BackgroundBaptista‐de‐Souza, D., Tavares, L. R. R., Furuya-da-Cunha, E. M., de Oliveira, P. E. C., Canto‐de‐Souza, L., Nunes‐de‐Souza, R. L., & Canto‐de‐Souza, A. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00260 · Cited by 15
“The influence of emotional states such as anxiety and fear on pain reaction has been widely investigated in animal models (Siegfried et al., 1990; Fields, 2004; Baptista et al., 2009; Furuyada-Cunha et al., 2016) and the exposure to the elevated plusmaze (EPM), a widely used animal model of anxiety (Lister, 1987; Caro…”
MethodSiemian, J. N., Borja, C. B., Sarsfield, S., Kisner, A., & Aponte, Y. (2019) · Scientific Reports · doi:10.1038/s41598-019-48537-y · Cited by 19
Microglia in the Primary Somatosensory Barrel Cortex Mediate Trigeminal Neuropathic Pain
Wang, Y., Cao, P., Mei, L., Yin, W., Mao, Y., Niu, C., Zhang, Z., & Tao, W. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.05.034 · Cited by 17
Lin, Y., Bai, Y., Liu, P., Yang, X., Qin, W., Gu, J., Ding, D., Tian, J., & Wang, M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184896 · Cited by 12
Ozdemir, E., Demirkazık, A., Gursoy, S., Taskıran, A., Kılınç, O., & Arslan, G. (2017) · General Physiology and Biophysics · doi:10.4149/gpb_2017008 · Cited by 14
“The nociceptive perception is the result of complicated interaction between the primary pain ascending pathways connecting spinal cord and midbrain pain centres, and descending regulatory pathways (Fields 2004).”
BackgroundTexture features of periaqueductal gray in the patients with 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/s10194-017-0727-0 · Cited by 18
“PAG, as a substantial descending pain modulatory center, exerts inhibition and facilitation control on nociceptive transmission in the dorsal horn and trigeminal nucleus [4], and the modulatory mechanism was exerted by descending PAG-RVM (rostral ventromedial medulla) pathway contributing to central sensitization and…”
BackgroundThe Neural Correlates of Chronic Symptoms of Vertigo Proneness in Humans
Alsalman, O. A., Ost, J., Vanspauwen, R., Blaivie, C., Ridder, D. D., & Vanneste, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0152309 · Cited by 15
“It is part of the pain inhibitory antinociceptive descending pathway [69, 70], which is deficient in general pain syndromes such as fibromyalgia [71].”
BackgroundMakovec, M. R., Vintar, N., & Makovec, S. (2014) · Slovenian Journal of Public Health · doi:10.1515/sjph-2015-0001 · Cited by 10
“That is why pain has been understood as a multifactorial illness with bio-psycho-social components (8).”
BackgroundIto, K., Yoshikawa, M., Maeda, M., Jin, X., Takahashi, S., Matsuda, M., Tamaki, R., Kobayashi, H., Suzuki, T., & Hashimoto, A. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.02.068 · Cited by 14
Bradykinin into amygdala induces thermal hyperalgesia in rats
Dalmolin, G. D., Silva, C. R., Bellé, N. A. V., Rubin, M. A., Mello, C. F., Calixto, J. Β., & Ferreira, J. (2007) · Neuropeptides · doi:10.1016/j.npep.2006.12.007 · Cited by 17
δ-opioid receptor-mediated actions on rostral ventromedial medulla neurons
Marinelli, S., Connor, M., Schnell, S., Christie, M., Wessendorf, M., & Vaughan, C. W. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.01.015 · Cited by 14
A neural circuit for sex-dependent conditioned pain hypersensitivity in mice
Zhang, M., Ni, Z., Ma, J., Liu, A., Liu, Y., Lou, Q., Dong, W., Zhang, Z., Li, J., & Cao, P. (2025) · Nature Communications · doi:10.1038/s41467-025-58851-x · Cited by 10
“Additionally, GABA vlPAG neurons play a central role in endogenous opioid-induced analgesia 43 – 45 .”
Li, J. Z., Mills, E. P., Osborne, N. R., Cheng, J. C., Sanmugananthan, V. V., El‐Sayed, R., Besik, A., Kim, J. A., Bosma, R. L., Rogachov, A., et al. (2024) · Pain · doi:10.1097/j.pain.0000000000003478 · Cited by 14
Navratilova, E., Qu, C., Ji, G., Neugebauer, V., Guerrero, M. A., Rosen, H., Roberts, E., & Porreca, F. (2023) · Anesthesiology · doi:10.1097/aln.0000000000004773 · Cited by 18
“28 The ,45-47 Opioids preferentially modulate aversive qualities of pain within corticolimbic circuits, with preservation of physiologic nociceptive inputs allowing safety from self-harm in patients.”
BackgroundBrain structural and functional alterations related to anxiety in allergic asthma
Dehdar, K., & Raoufy, M. R. (2023) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.110727 · Cited by 15
“regulation of pain sensations (Fields, 2004; Tracey and Mantyh, 2007), increased GMV in the PAG might contribute to the reduced perceived”
Liu, W., Jiang, P., & Qiu, L.-J. (2022) · Journal of Molecular Neuroscience · doi:10.1007/s12031-022-01989-w · Cited by 13
“Opioids such as morphine have been applied for the treatment of severe pain (Parsadaniantz et al. 2015; Fields 2004).”
BackgroundAtlas, L. Y., Dildine, T. C., Palacios‐Barrios, E. E., Yu, Q., Reynolds, R. C., Banker, L., Grant, S. S., & Pine, D. S. (2022) · eLife · doi:10.7554/elife.73353 · Cited by 20
“Together with the periaqueductal gray (PAG), the RVM is a key component of the descending pain modulatory system (Fields, 2004; Fields, 2006), which regulates the release of endogenous opioids that can block ascending pain signals, a process thought to be critical for expectancy- based placebo analgesia (Levine et al.”
BackgroundPlacebo-induced pain reduction is associated with negative coupling between brain networks at rest
Wagner, I. C., Rütgen, M., Hummer, A., Windischberger, C., & Lamm, C. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.117024 · Cited by 16
Genetic factors associated with empathy in humans and mice
Keum, S., & Shin, H. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.01.029 · Cited by 14
“the endogenous opioid system is intimately involved in the modulation of pain and emotions (Fields, 2004; Nummenmaa et al., 2008).”
BackgroundTavares, L. R. R., Baptista‐de‐Souza, D., & Canto‐de‐Souza, A. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.03.008 · Cited by 15
“This neuronal inhibition of the amygdaloid complex might result in an inactivation of crucial neurotransmitter systems of the descending inhibitory pain circuitry (Fields, 2004; McGaraughty et al., 2004), triggering an exacerbation of the sensory nociceptive response.”
BackgroundContreras-Hernández, E., Chávez, D., Hernández, E., Velazquez, E. J., Reyes, P., Béjar, J., Martín, M., Ulises Cortés, A., Glusman, S., & Rudomin, P. (2018) · The Journal of Physiology · doi:10.1113/jp275228 · Cited by 13
“Based on these observations we assumed that the analysis of the changes produced by nociceptive stimulation on the correlation and coherence between the ongoing CDPs and intraspinal field potentials (IFPs) would be an appropriate mean to reveal relevant features of the supraspinal modulation of the patterns of functio…”
BackgroundSalas, R., Ramirez, K., Vanegas, H., & Vázquez, E. (2016) · Brain Research · doi:10.1016/j.brainres.2016.10.001 · Cited by 21
Kadiri, N., Rodeau, J., Schlichter, R., & Hugel, S. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07846.x · Cited by 12
“Alternatively, an excitatory effect of NT at the spinal cord level could activate descending inhibitory controls from the brainstem (Le Bars, 2002; Fields, 2004).”
BackgroundA septo-hypothalamic-medullary circuit directs stress-induced analgesiaPreprint
Shah, D. P., Sharma, P. R., Agarwal, R., & Barik, A. (2024) · eLife · doi:10.7554/elife.96724 · Cited by 6
“Importantly, SIA is opioid-dependent (Finn, 2017; Lewis et al., 1981; Vaccarino et al., 1992) (Figure S8A), and RVM is a major substrate for endogenous opioids (Fields, 2004).”
Shifting the perspective: how positive thinking can help diminish the negative effects of pain
Boselie, J. J. L. M., & Peters, M. L. (2023) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2022-0129 · Cited by 15
Posa, L., Gregorio, D. D., He, Q., López-Canúl, M., Darcq, E., Rullo, L., Pearl-Dowler, L., Luongo, L., Candeletti, S., Romualdi, P., et al. (2022) · Journal of Pineal Research · doi:10.1111/jpi.12825 · Cited by 12
“A large body of literature suggests that MORs are localized at the somatodendritic level of ON‐cell of RVM (receiving inputs from PAG glutamatergic neurons) and at the GABA‐releasing presynaptic terminal of the OFF neurons.(9,11,60) Indeed, OFF‐cells are activated by local infusion of either MOR selective ligands or t…”
BackgroundMethodPati, D., & Kash, T. L. (2021) · Journal of Neurophysiology · doi:10.1152/jn.00251.2021 · Cited by 13
Pain, placebo, and cognitive penetration
Shevlin, H., & Friesen, P. (2020) · Mind & Language · doi:10.1111/mila.12292 · Cited by 16
Colloca, L. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.04.001 · Cited by 15
The altered Granger causality connection among pain-related brain networks in migraine
Ning, Y., Zheng, R., Li, K., Zhang, Y., Lyu, D., Jia, H., Ren, Y., & Zou, Y. (2018) · Medicine · doi:10.1097/md.0000000000010102 · Cited by 16
Evaluation of Abbott’s BurstDR stimulation device for the treatment of chronic pain
Deer, T. R., Campos, L. W., & Pope, J. E. (2017) · Expert Review of Medical Devices · doi:10.1080/17434440.2017.1330147 · Cited by 12
The pathophysiological role of serotonin receptor systems in opioid analgesia and tolerance
Ozdemir, E. (2017) · doi:10.18203/2319-2003.ijbcp20170312 · Cited by 12
Placebo Response: Relevance to the Rheumatic Diseases
Pollo, A., & Benedetti, F. (2008) · Rheumatic Disease Clinics of North America · doi:10.1016/j.rdc.2008.04.002 · Cited by 10
“the hypothalamus, and the central nucleus of the amygdala [68].”
BackgroundPlacebo analgesia: Friend or foe?
Price, D. D., Fillingim, R. B., & Robinson, M. E. (2006) · Current Rheumatology Reports · doi:10.1007/s11926-006-0035-1 · Cited by 15
Mu Opioid Receptor Mediated Analgesia and Reward
Fields, H. L. (2010) · Humana Press eBooks · doi:10.1007/978-1-60761-993-2_10 · Cited by 14
Self-citationThe Endogenous Neuromodulation System
Basbaum, A. I., Braz, J. M., Ossipov, M. H., & Porreca, F. (2009) · Elsevier eBooks · doi:10.1016/b978-0-12-374248-3.00023-9 · Cited by 11
Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson’s disease
Grivet, Z., Aby, F., Verboven, A., Bouali‐Benazzouz, R., Sueur, B., Maingret, F., Naudet, F., Dhellemmes, T., Deurwaerdère, P. D., Benazzouz, A., et al. (2025) · npj Parkinson s Disease · doi:10.1038/s41531-024-00857-1 · Cited by 15
Harding, E. K., Zhang, Z., Canet-Pons, J., Stokes-Heck, S., Trang, T., & Zamponi, G. W. (2024) · iScience · doi:10.1016/j.isci.2024.109972 · Cited by 9
“44 GABAergic neurons in the vlPAG are also involved in anxiety and fear learning, 28,45–47 regulation of sleep and arousal, 6,48,49 prey hunting, 50 and feeding behaviors.”
Vanneste, S., & Ridder, D. D. (2023) · Brain stimulation · doi:10.1016/j.brs.2023.07.058 · Cited by 14
“In addition, a descending pain inhibitory pathway [6] involves the rostral and pregenual anterior cingulate cortex (pgACC), hypothalamus, and periaquaductal gray (PAG).”
BackgroundYu, X., Abdul, M., Fan, B., Zhang, L., Xing, L., Wu, Y., Fu, H., Lin, Q., & Meng, H. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.134774 · Cited by 21
Preoccupation in an Early-Romantic Relationship Predicts Experimental Pain Relief
Nilakantan, A. S., Younger, J., Aron, A. P., & Mackey, S. (2014) · Pain Medicine · doi:10.1111/pme.12422 · Cited by 17
“The analgesic benefits of preoccupation may also extend beyond the context of love (27,28).”
BackgroundOpioid microinjection into raphe magnus modulates cardiorespiratory function in mice and rats
Hellman, K. M., Mendelson, S., Mendez-Duarte, M. A., Russell, J. L., & Mason, P. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00140.2009 · Cited by 10
Controllability changes pain perception by increasing the precision of expectations
Habermann, M., & Büchel, C. (2025) · Nature Communications · doi:10.1038/s41467-025-66038-7 · Cited by 12
The ARCH model: a neuroevolutionary framework for behavioral execution
Rahman, T., Zorumski, C. F., & Meloy, J. R. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1669530 · Cited by 10
Wei, H.-R., Tang, L. F., Yang, X., Chen, C., Li, L.-X., Mao, Y., Wang, D., Kang, F., Qun, S., Zhang, Z., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113804 · Cited by 10
Duan, Y.-W., Li, Q., Zhou, Y., Chen, S., Li, Y., & Zang, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242015454 · Cited by 12
“The hyper-excitability of the ACC can trigger changes in spinal networks [35], thus facilitating spinal nociceptive transmission through the periaqueductal gray (PAG) and rostral ventral medulla (RVM) or through the ACC’s direct corticospinal projections [3,4,36–38].”
BackgroundFollansbee, T., Domocos, D. T., Nguyen, E. K., Nguyen, A., Bountouvas, A., Velasquez, L., Carstens, M. I., Takanami, K., Ross, S. E., & Carstens, E. E. (2022) · eLife · doi:10.7554/elife.69626 · Cited by 21
Medullary kappa-opioid receptor neurons inhibit pain and itch through a descending circuitPreprint
Nguyen, E., Smith, K. M., Cramer, N., Holland, R. A., Bleimeister, I. H., Flores-Felix, K., Silberberg, H., Keller, A., Pichon, C. E. L., & Ross, S. E. (2022) · bioRxiv · doi:10.1101/2022.02.08.479623 · Cited by 10
“Neurons in the RVM have been identified through extensive electrophysiological and pharmacological studies.(4,9) For example, single unit recordings have provided significant insight into three types of neurons in the RVM: ON, OFF, and NEUTRAL cells based on their firing responses to noxious stimulation and sensitivit…”
MethodGluA1 in Central Amygdala Promotes Opioid Use and Reverses Inhibitory Effect of Pain
Hou, Y.-Y., Cai, Y.-Q., & Pan, Z. Z. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.11.032 · Cited by 11
“Pain is an unpleasant and aversive experience involving sensory perception of a harmful stimulus, negative emotions of affect and behavioral responses of avoidance (Fields, 2004; Baliki and Apkarian, 2015).”
BackgroundInfluentialThe pain alarm response - an example of how conscious awareness shapes pain perception
Pontén, M., Fust, J., D’Onofrio, P., van Dorp, R., Sunnergård, L., Ingre, M., Axelsson, J., & Jensen, K. B. (2019) · Scientific Reports · doi:10.1038/s41598-019-48903-w · Cited by 10
The effects of aging on hydromorphone-induced thermal antinociception in healthy female cats
Simon, B., Scallan, E., Monteiro, B., & Steagall, P. (2019) · PAIN Reports · doi:10.1097/pr9.0000000000000722 · Cited by 10
“Opioids produce potent analgesic effects at the supraspinal (thalamus, hypothalamus, insular cortex, amygdala, cingulate gurus, locus coeruleus, and periaqueductal gray) and spinal (laminae I and II of the dorsal horn) levels(5,28) via the activation of descending inhibitory pathways, inhibition of Ca(21) influx from…”
BackgroundBrainstem Opioidergic System Is Involved in Early Response to Experimental SAH
Cetas, J., McFarlane, R., Kronfeld, K., Smitasin, P. J., Liu, J. J., & Raskin, J. S. (2015) · Translational Stroke Research · doi:10.1007/s12975-014-0378-2 · Cited by 10
“Activation of the μ-opioid receptor results in direct inhibition of one class of cells within the RVM and disinhibition of a second class of cells through reduced presynaptic release of GABA [23, 34].”
BackgroundShu, H., Hayashida, M., Arita, H., Huang, W., Xiao, L., Chiba, S., Sekiyama, H., & Hanaoka, K. (2008) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2008.07.009 · Cited by 9
Purinergic Receptor Immunoreactivity in the Rostral Ventromedial Medulla
Close, L. N., Cetas, J., Heinricher, M., & Selden, N. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.08.044 · Cited by 10
“The exact role of serotonin neurons in nociceptive modulation within the RVM remains unknown (Fields, 2004, Braz and Basbaum, 2008).”
BackgroundResultDo hypnotic analgesic interventions contain placebo effects?
Price, D. (2006) · Pain · doi:10.1016/j.pain.2006.04.021 · Cited by 10
“If so, should we call them ‘‘placebo effects’’? Neurobiologists and psychologists have independently suggested that placebo mechanisms reflect emotional regulation, an idea roughly similar to but not identical with the older idea that placebo responses reflect anxiety reduction (Price, 1999; Vase et al., 2003, 2005; F…”
ResultFundamentals of Burst Stimulation of the Spinal Cord and Brain
Ridder, D. D., Vancamp, T., & Vanneste, S. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-805353-9.00014-0 · Cited by 10
“…(Bushnell et al., 2013; Price, 2000) (i.e., the unpleasantness) (Bushnell et al., 2013; Rainville et al., 1997), the lateral pathway encodes the discriminatory/sensory (Bushnell et al., 2013) component, and the descending pathway suppresses ongoing pain in a statedependent manner (Fields, 2004).”
BackgroundInfluentialMolecular Imaging of Opioid System in Idiopathic Parkinson's Disease
Thobois, S., Brefel‐Courbon, C., Bars, D. L., & Sgambato, V. (2018) · International review of neurobiology · doi:10.1016/bs.irn.2018.07.029 · Cited by 14
Chen, J. (2011) · Neuroscience Bulletin · doi:10.1007/s12264-011-0139-0 · Cited by 31
“[34] Fields HL.”
Deconstruction of a spino-brain–spinal cord circuit that drives chronic pain
Wang, Q., Lee, J. H., Nachtrab, G. T., Yuan, Y., Yuan, L., Qi, W., Mohr, M. A., Xiong, J., Horowitz, M., & Chen, X. (2026) · Nature · doi:10.1038/s41586-026-10296-y · Cited by 8
“Current models emphasize the role of the PAG to RVM pathway in descending pain modulation 1–3 .”
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“with a high concentration of opioid peptides (based on [37]).”
BackgroundSalvage Therapy With Burst Spinal Cord Stimulation for Chronic Pancreatitis: A Case Report
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“Pain transmission has been studied, and it has been established that there is a lateral pathway that would be responsible for the sensory or discriminatory component of pain,(22) a medial pathway responsible for the emotional and affective components of pain,(23) and an inhibitory descending path, which would control…”
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Subjective utility moderates bidirectional effects of conflicting motivations on pain perception
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“The different experimental manipulations and conditions, comprising (1) the category monetary wins or losses (low, high, no), (2) electrocutaneous stimulation (no stimulation, stimulation), (3) participant’s choice”
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“Endogenous opioids play an important inhibitory role in pain modulating mechanisms (Fields, 2004; Curatolo et al., 2006).”
Connections from the rat dorsal column nuclei (DCN) to the periaqueductal gray matter (PAG)
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“It is known that rodent and human opioid receptors are pharmacologically comparable [19] and that at the brainstem level opioid circuits have similar mechanisms in both species [19] and [20].”
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Capsicum: A Natural Pain Modulator
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Positive and Negative Emotions and Placebo Analgesia
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Top-down control of the descending pain modulatory system drives multimodal placebo analgesia
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“Opioid receptors and their ligands are widely expressed in the pain pathway, indicating the potential role of endogenously produced opioid peptides in modulating pain processing [1 ,2 ].”
BackgroundOpioidergic activation of descending pain inhibitory system underlies placebo analgesia
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“The mPFC sends monosynaptic excitatory projections into the ventrolateral periaqueductal gray (vlPAG), a key node nucleus of the descending pain inhibitory system (23), for modulating pain 35 processing (24-26).”
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Targeting Chemokines and Chemokine GPCRs to Enhance Strong Opioid Efficacy in Neuropathic Pain
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“engagement of the endogenous opioidergic systems to counter increased pronociceptive signalling in models of chronic pain and align with evidence from clinical pain states.(24,30,34) Unlike Wistar rats, both systemic naloxone or CTAP significantly lowered hind”
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Unconscious and conscious mediation of analgesia and hyperalgesia
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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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