Chronic CRF1receptor blockade reduces heroin intake escalation and dependence‐induced hyperalgesia
Open accessAbstract
Opioids represent effective drugs for the relief of pain, yet chronic opioid use often leads to a state of increased sensitivity to pain that is exacerbated during withdrawal. A sensitization of pain‐related negative affect has been hypothesized to closely interact with addiction mechanisms. Neuro‐adaptive changes occur as a consequence of excessive opioid exposure, including a recruitment of corticotropin‐releasing factor (CRF) and norepinephrine (NE) brain stress systems. To better understand the mechanisms underlying the transition to dependence, we determined the effects of functional antagonism within these two systems on hyperalgesia‐like behavior during heroin withdrawal utilizing models of both acute and chronic dependence. We found that passive or self‐administered heroin produced a significant mechanical hypersensitivity. During acute opioid dependence, systemic administration of the CRF1 receptor antagonist MPZP(20 mg/kg) alleviated withdrawal‐induced mechanical hypersensitivity. In contrast, several functional adrenergic system antagonists (clonidine, prazosin, propranolol) failed to alter mechanical hypersensitivity in this state. We then determined the effects of chronic MPZP or clonidine treatment on extended access heroin self‐administration and found that MPZP, but not clonidine, attenuated escalation of heroin intake, whereas both drugs alleviated chronic dependence‐associated hyperalgesia. These findings suggest that an early potentiation of CRF signaling occurs following opioid exposure that begins to drive both opioid‐induced hyperalgesia and eventually intake escalation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Systemic CRF1 receptor antagonist blocks withdrawal hyperalgesia in animals with extended access to heroin.
“Consistent with this observation, hyperalgesia during withdrawal in animals that developed compulsive-like responding with extended access to heroin was blocked by the systemic administration of a CRF 1 receptor antagonist (Edwards et al., 2012b;Park et al., 2015).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Park et al., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Quantitative assessment of tactile allodynia in the rat paw
Chaplan, S. R., Bach, F. W., Pogrel, J. W., Chung, J. M., & Yaksh, T. L. (1994) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(94)90144-9 · Cited by 7,740 · see citing works
Addiction and the brain antireward system
Koob, G. F., & Le Moal, M. (2008) · Annual Review of Psychology · doi:10.1146/annurev.psych.59.103006.093548 · Cited by 1,457 · see citing works
Self-citationThe prevalence of chronic pain in United States adults: Results of an Internet-based survey
Johannes, C. B., Le, T. K., Zhou, X., Johnston, J. A., & Dworkin, R. H. (2010) · The Journal of Pain · doi:10.1016/j.jpain.2010.07.002 · Cited by 1,252 · see citing works
Opioid-induced Hyperalgesia: A Qualitative Systematic Review
Angst, M. S., & Clark, J. D. (2006) · Anesthesiology · doi:10.1097/00000542-200603000-00025 · Cited by 1,188 · see citing works
A Role for Brain Stress Systems in Addiction
Koob, G. F. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.012 · Cited by 1,056 · see citing works
Self-citationCorticotropin-releasing factor, norepinephrine, and stress
Koob, G. F. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00164-x · Cited by 629 · see citing works
Self-citationNeurobiological mechanisms in the transition from drug use to drug dependence
Koob, G. F., Ahmed, S. H., Boutrel, B., Chen, S. A., Kenny, P. J., Markou, A., O’Dell, L. E., Parsons, L. H., & Sanna, P. P. (2003) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2003.11.007 · Cited by 576 · see citing works
Self-citationUnmasking the tonic-aversive state in neuropathic pain
King, T. E., Vera–Portocarrero, L. P., Gutierrez, T., Vanderah, T. W., Dussor, G. O., Lai, J. Y., Fields, H. L., & Porreca, F. (2009) · Nature Neuroscience · doi:10.1038/nn.2407 · Cited by 570 · see citing works
Fishbain, D. A., Cole, B., Lewis, J. E., Rosomoff, H. L., & Rosomoff, R. S. (2007) · Pain Medicine · doi:10.1111/j.1526-4637.2007.00370.x · Cited by 565 · see citing works
Blaudszun, G., Lysakowski, C., Elia, N., & Tramèr, M. R. (2012) · Anesthesiology · doi:10.1097/aln.0b013e31825681cb · Cited by 557 · see citing works
Compulsive Drug‐Seeking Behavior and Relapse: Neuroadaptation, Stress, and Conditioning Factors
WEISS, F., CICCOCIOPPO, R., PARSONS, L. H., KATNER, S., LIU, X., ZORRILLA, E. P., VALDEZ, G. R., BEN‐SHAHAR, O., ANGELETTI, S., & RICHTER, R. R. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb03556.x · Cited by 430 · see citing works
Persistent Increase in the Motivation to Take Heroin in Rats with a History of Drug Escalation
Ahmed, S. H. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00133-5 · Cited by 361 · see citing works
Alcohol dependence as a chronic pain disorder
Egli, M., Koob, G. F., & Edwards, S. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.07.010 · Cited by 347 · see citing works
Self-citationCélèrier, E., Laulin, J.-P., Corcuff, J.-B., Le Moal, M., & Simonnet, G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-11-04074.2001 · Cited by 315 · see citing works
Pain intolerance in opioid-maintained former opiate addicts: effect of long-acting maintenance agent
Compton, P., Charuvastra, V. C., & Ling, W. (2001) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(00)00200-3 · Cited by 311 · see citing works
Relapse to drug-seeking: neural and molecular mechanisms
Self, D. W., & Nestler, E. J. (1998) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(98)00065-9 · Cited by 296 · see citing works
Nackley, A. G., Tan, K. S., Fecho, K., Flood, P. M., Diatchenko, L. B., & Maixner, W. D. (2006) · Pain · doi:10.1016/j.pain.2006.09.022 · Cited by 281 · see citing works
Opioid-induced hyperalgesia: abnormal or normal pain?
Simonnet, G., & Rivat, C. (2003) · NeuroReport · doi:10.1097/00001756-200301200-00001 · Cited by 273 · see citing works
Conditioned Withdrawal Drives Heroin Consumption and Decreases Reward Sensitivity
Kenny, P. J., Chen, S. A., Kitamura, O., Markou, A., & Koob, G. F. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0740-06.2006 · Cited by 268 · see citing works
Self-citationAston‐Jones, G., Delfs, J. M., Druhan, J. P., & Zhu, Y. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb09284.x · Cited by 251 · see citing works
Heinrichs, S. C., Menzaghi, F., Schulteis, G., Koob, G. F., & Stinus, L. (1995) · Behavioural Pharmacology · doi:10.1097/00008877-199501000-00011 · Cited by 226 · see citing works
Self-citationOpioids, pain, the brain, and hyperkatifeia: a framework for the rational use of opioids for pain
Shurman, J., Koob, G. F., & Gutstein, H. B. (2010) · Pain Medicine · doi:10.1111/j.1526-4637.2010.00881.x · Cited by 215 · see citing works
Self-citationMALDONADO, R. (1997) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(95)00061-5 · Cited by 213 · see citing works
Smith, R. J., & Aston-Jones, G. (2008) · Brain Structure and Function · doi:10.1007/s00429-008-0191-3 · Cited by 206 · see citing works
Shaham, Y., Highfield, D., Delfs, J., Leung, S., & Stewart, J. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00899.x · Cited by 201 · see citing works
Edwards, S., Vendruscolo, L. F., Schlosburg, J. E., Misra, K., Wee, S., Park, P. E., Schulteis, G., & Koob, G. F. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.11.006 · Cited by 158 · see citing works
Self-citationThe Doctor's Dilemma: Opiate Analgesics and Chronic Pain
Fields, H. L. (2011) · Neuron · doi:10.1016/j.neuron.2011.02.001 · Cited by 157 · see citing works
Neurobiology of dysregulated motivational systems in drug addiction
Edwards, S., & Koob, G. F. (2010) · Future Neurology · doi:10.2217/fnl.10.14 · Cited by 157 · see citing works
Self-citationLong-lasting increased pain sensitivity in rat following exposure to heroin for the first time
Laulin, J., Larcher, A., Célèrier, E., Moal, M. L., & Simonnet, G. (1998) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1998.00083.x · Cited by 156 · cited 4× · see citing works
“This dose was previously shown to induce mechanical hyperalgesia during heroin withdrawal (Laulin et al. 1998) that progressively increases after repeated, intermittent heroin injections (Celerier et al.”
BackgroundInfluentialEscalation of drug self-administration as a hallmark of persistent addiction liability
Edwards, S., & Koob, G. F. (2013) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e3283644d15 · Cited by 151 · see citing works
Self-citationMcNally, G. P., & Akil, H. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00105-7 · Cited by 141 · see citing works
Pain-Related Anxiety-Like Behavior Requires CRF1 Receptors in the Amygdala
Ji, G., Fu, Y., Ruppert, K. A., & Neugebauer, V. (2007) · Molecular Pain · doi:10.1186/1744-8069-3-13 · Cited by 138 · see citing works
Neurobiology of addiction versus drug use driven by lack of choice
Ahmed, S. H., Lenoir, M., & Guillem, K. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.01.028 · Cited by 135 · see citing works
Noradrenaline Modulates Transmission at a Central Synapse by a Presynaptic Mechanism
Delaney, A., Crane, J. W., & Sah, P. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.022 · Cited by 125 · see citing works
Ji, G., & Neugebauer, V. (2007) · Journal of Neurophysiology · doi:10.1152/jn.00135.2007 · Cited by 123 · see citing works
Pharmacology of Opioid and Nonopioid Analgesics in Chronic Pain States
Martin, T. J., & Eisenach, J. C. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29197-7 · Cited by 123 · see citing works
Eisenach, J. C., Hood, D. D., & Curry, R. S. (1998) · Anesthesia & Analgesia · doi:10.1213/00000539-199809000-00018 · Cited by 122 · see citing works
A Vaccine Strategy that Induces Protective Immunity against Heroin
Stowe, G. N., Vendruscolo, L. F., Edwards, S., Schlosburg, J. E., Misra, K., Schulteis, G., Mayorov, A. V., Zakhari, J. S., Koob, G. F., & Janda, K. D. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200461m · Cited by 116 · see citing works
Self-citationA Genetic Analysis of Opioid-induced Hyperalgesia in Mice
Liang, D., Liao, G., Wang, J., Usuka, J., Guo, Y., Peltz, G., & Clark, J. D. (2006) · Anesthesiology · doi:10.1097/00000542-200605000-00023 · Cited by 115 · see citing works
Martin, T. J., Kim, S. A., Buechler, N. L., Porreca, F., & Eisenach, J. C. (2007) · Anesthesiology · doi:10.1097/00000542-200702000-00020 · Cited by 109 · see citing works
Reinforcement processes in opiate addiction: A homeostatic model
Schulteis, G., & Koob, G. F. (1996) · Neurochemical Research · doi:10.1007/bf02532385 · Cited by 108 · see citing works
Self-citationChen, S. A., O'Dell, L. E., Hoefer, M. E., Greenwell, T. N., Zorrilla, E. P., & Koob, G. F. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301008 · Cited by 97 · see citing works
Self-citationSupply of a Nondrug Substitute Reduces Escalated Heroin Consumption
Lenoir, M., & Ahmed, S. H. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301602 · Cited by 96 · see citing works
MPZP: A novel small molecule corticotropin-releasing factor type 1 receptor (CRF1) antagonist
RICHARDSON, H., ZHAO, Y., Fekete, É. M., FUNK, C., Wirsching, P., Janda, K. D., Zorrilla, E. P., & Koob, G. F. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.10.008 · Cited by 95 · see citing works
Self-citationConditioned place aversion is a highly sensitive index of acute opioid dependence and withdrawal
Azar, M. R., Jones, B. C., & Schulteis, G. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1514-y · Cited by 91 · see citing works
Self-citationGreenwell, T. N., Funk, C. K., Cottone, P., Richardson, H. N., Chen, S. A., Rice, K. C., Zorrilla, E. P., & Koob, G. F. (2009) · Addiction Biology · doi:10.1111/j.1369-1600.2008.00142.x · Cited by 87 · see citing works
Self-citationConditioned Place Preference Reveals Tonic Pain in an Animal Model of Central Pain
Davoody, L., Quiton, R. L., Lucas, J. M., Ji, Y., Keller, A., & Masri, R. M. (2011) · Journal of Pain · doi:10.1016/j.jpain.2011.01.010 · Cited by 83 · see citing works
Elevated startle during withdrawal from acute morphine: a model of opiate withdrawal and anxiety
Harris, A. C., & Gewirtz, J. C. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1573-0 · Cited by 81 · see citing works
Safieh‐Garabedian, B., Poole, S., Haddad, J. J., Massaad, C. A., Jabbur, S. J., & Saadé, N. E. (2002) · Neuropharmacology · doi:10.1016/s0028-3908(02)00028-x · Cited by 80 · see citing works
Escalation patterns of varying periods of heroin access
Vendruscolo, L. F., Schlosburg, J. E., Misra, K., Chen, S. A., Greenwell, T. N., & Koob, G. F. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.03.004 · Cited by 79 · see citing works
Self-citationNegative Reinforcement Reveals Non-Evoked Ongoing Pain in Mice With Tissue or Nerve Injury
He, Y. Z., Tian, X., Hu, X., Porreca, F., & Wang, Z. J. (2012) · Journal of Pain · doi:10.1016/j.jpain.2012.03.011 · Cited by 77 · see citing works
Brain reward deficits accompany naloxone-precipitated withdrawal from acute opioid dependence
LIU, J., & Schulteis, G. (2004) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2004.06.006 · Cited by 76 · see citing works
Self-citationZhang, Z., & Schulteis, G. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.01.013 · Cited by 71 · see citing works
Self-citationRothwell, P. E., Thomas, M. J., & Gewirtz, J. C. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.56 · Cited by 52 · see citing works
Modulation of remifentanil-induced postinfusion hyperalgesia by the β-blocker propranolol in humans
Chu, L. F., Cun, T., Ngai, L. K., Kim, J. E., Zamora, A. K., Young, C. A., Angst, M. S., & Clark, J. D. (2012) · Pain · doi:10.1016/j.pain.2012.01.014 · Cited by 50 · see citing works
Schulteis, G., Heyser, C. J., & Koob, G. F. (1999) · Behavioural Pharmacology · doi:10.1097/00008877-199905000-00001 · Cited by 49 · see citing works
Self-citationThe β2 adrenergic receptor regulates morphine tolerance and physical dependence
Liang, D., Shi, X., Li, X., Li, J., & Clark, J. D. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.03.037 · Cited by 48 · see citing works
Eisenach, J. C., Hood, D. D., & Curry, R. S. (1998) · Anesthesia & Analgesia · doi:10.1097/00000539-199809000-00018 · Cited by 48 · see citing works
Age-dependent Responses to Nerve Injury– induced Mechanical Allodynia
Ririe, D. G., & Eisenach, J. C. (2006) · Anesthesiology · doi:10.1097/00000542-200602000-00021 · Cited by 45 · see citing works
Edwards, S., Graham, D. L., Whisler, K. N., & Self, D. W. (2008) · Synapse · doi:10.1002/syn.20601 · Cited by 41 · see citing works
Self-citationPark, P. E., Vendruscolo, L. F., Schlosburg, J. E., Edwards, S., Schulteis, G., & Koob, G. F. (2013) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145713000308 · Cited by 37 · see citing works
Self-citationConway, E. L., & Jarrott, B. (1980) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1980.tb10960.x · Cited by 33 · see citing works
Tierney, C., Nadaud, D., Koenig‐Bérard, E., & Stinus, L. (1988) · The American Journal of Cardiology · doi:10.1016/0002-9149(88)90462-6 · Cited by 27 · see citing works
Kim, S. K., Min, B.-I., Kim, J. H., Hwang, B. G., Yoo, G. Y., Park, D. S., & Na, H. S. (2005) · Brain Research · doi:10.1016/j.brainres.2005.01.051 · Cited by 26 · see citing works
Chen, D., Qu, F., He, X., Wang, Y., & Wen, W.-W. (2010) · Brain Research · doi:10.1016/j.brainres.2010.07.069 · Cited by 15 · see citing works
Bujalska‐Zadrożny, M., Araźna, M., Makulska-Nowak, H. E., & Gumułka, S. W. (2008) · PubMed · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Strang, J., Volkow, N. D., Degenhardt, L., Hickman, M., Johnson, K., Koob, G. F., Marshall, B. D. L., Tyndall, M., & Walsh, S. L. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0137-5 · Cited by 639 · see citing works
Self-citationEndogenous and Exogenous Opioids in Pain
Corder, G. F., Castro, D. C., Bruchas, M. R., & Scherrer, G. (2018) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-080317-061522 · Cited by 511 · see citing works
Neurobiology of opioid addiction: Opponent process, hyperkatifeia, and negative reinforcement
Koob, G. F. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.023 · Cited by 477 · see citing works
Self-citationDrug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development
Koob, G. F. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000083 · Cited by 337 · see citing works
Self-citationNeuroscience of Addiction: Relevance to Prevention and Treatment
Volkow, N. D., & Boyle, M. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.17101174 · Cited by 355 · see citing works
Addiction and Stress: An Allostatic View
Koob, G. F., & Schulkin, J. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.008 · Cited by 315 · see citing works
Self-citationThe role of glucagon‐like peptide 1 (GLP‐1) in addictive disorders
Klausen, M. K., Thomsen, M., Wortwein, G., & Fink‐Jensen, A. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15677 · Cited by 259 · see citing works
Sugar addiction: the state of the science
Westwater, M. L., Fletcher, P. C., & Ziauddeen, H. (2016) · Zeitschrift für Ernährungswissenschaft · doi:10.1007/s00394-016-1229-6 · Cited by 138 · see citing works
Allostatic mechanisms of opioid tolerance beyond desensitization and downregulation
Cahill, C. M., Walwyn, W., Taylor, A. M. W., Pradhan, A. A. A., & Evans, C. J. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.08.002 · Cited by 122 · see citing works
How Preclinical Models Evolved to Resemble the Diagnostic Criteria of Drug Addiction
Belin‐Rauscent, A., Fouyssac, M., Bonci, A., & Belin, D. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.01.004 · Cited by 118 · see citing works
The Opioid Crisis and the Future of Addiction and Pain Therapeutics
Coussens, N. P., Sittampalam, G. S., Jonson, S. G., Hall, M. D., Gorby, H. E., Tamiz, A. P., McManus, O. B., Felder, C. C., & Rasmussen, K. (2019) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.119.259408 · Cited by 107 · see citing works
Anhedonia, Hyperkatifeia, and Negative Reinforcement in Substance Use Disorders
Koob, G. F. (2022) · Current topics in behavioral neurosciences · doi:10.1007/7854_2021_288 · Cited by 89 · see citing works
Self-citationConsolidating the Circuit Model for Addiction
Lüscher, C., & Janak, P. H. (2021) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-092920-123905 · Cited by 88 · see citing works
Tolerance to alcohol: A critical yet understudied factor in alcohol addiction
Elvig, S. K., McGinn, M. A., Smith, C. C., Arends, M. A., Koob, G. F., & Vendruscolo, L. F. (2021) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2021.173155 · Cited by 86 · see citing works
Self-citationThe role of orexin-1 receptor signaling in demand for the opioid fentanyl
Fragale, J. E. C., Pantazis, C. B., James, M. H., & Aston‐Jones, G. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0420-x · Cited by 75 · see citing works
Male and female mice develop escalation of heroin intake and dependence following extended access
Towers, E. B., Tunstall, B. J., McCracken, M. L., Vendruscolo, L. F., & Koob, G. F. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.03.019 · Cited by 76 · see citing works
Self-citationBornebusch, A. B., Fink-Jensen, A., Wörtwein, G., Seeley, R. J., & Thomsen, M. (2019) · eneuro · doi:10.1523/eneuro.0443-18.2019 · Cited by 72 · see citing works
Oxycodone self-administration and withdrawal behaviors in male and female Wistar rats
Kimbrough, A., Kononoff, J., Simpson, S., Kallupi, M., Sedighim, S., Palomino, K., Conlisk, D., Momper, J. D., de Guglielmo, G., & George, O. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05479-y · Cited by 62 · see citing works
Pain Therapy Guided by Purpose and Perspective in Light of the Opioid Epidemic
Severino, A. L., Shadfar, A., Hakimian, J. K., Crane, O., Singh, G., Heinzerling, K. G., & Walwyn, W. M. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00119 · Cited by 65 · see citing works
Compulsive-Like Sufentanil Vapor Self-Administration in Rats
Vendruscolo, J. C. M., Tunstall, B. J., Carmack, S. A., Schmeichel, B. E., Lowery‐Gionta, E. G., Cole, M., George, O., Vandewater, S. A., Taffe, M. A., Koob, G. F., et al. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.172 · Cited by 54 · see citing works
Self-citationEndogenous Opiates and Behavior: 2015
Bodnar, R. J. (2016) · Peptides · doi:10.1016/j.peptides.2016.12.004 · Cited by 52 · see citing works
The affective dimension of pain as a risk factor for drug and alcohol addiction
LeBlanc, D. M., McGinn, M. A., Itoga, C. A., & Edwards, S. (2015) · Alcohol · doi:10.1016/j.alcohol.2015.04.005 · Cited by 44 · see citing works
Self-citationOpioid withdrawal: role in addiction and neural mechanisms
Monroe, S. C., & Radke, A. K. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06370-2 · Cited by 42 · see citing works
Bardo, M. T., Hammerslag, L. R., & Malone, S. G. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108567 · Cited by 32 · see citing works
Neuronal Correlates of Hyperalgesia and Somatic Signs of Heroin Withdrawal in Male and Female Mice
Álvarez-Bagnarol, Y., Marchette, R. C. N., Francis, C., Morales, M., & Vendruscolo, L. F. (2022) · eNeuro · doi:10.1523/eneuro.0106-22.2022 · Cited by 33 · see citing works
Self-citationκ-Opioid receptor antagonism reverses heroin withdrawal-induced hyperalgesia in male and female rats
Marchette, R. C. N., Gregory‐Flores, A., Tunstall, B. J., Carlson, E. R., Jackson, S. N., Sulima, A., Rice, K. C., Koob, G. F., & Vendruscolo, L. F. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100325 · Cited by 31 · see citing works
Self-citationPahng, A. R., Paulsen, R. I., McGinn, M. A., Edwards, K. N., & Edwards, S. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.09.055 · Cited by 29 · see citing works
Self-citationReinforcement principles for addiction medicine; from recreational drug use to psychiatric disorder
Edwards, S. (2015) · Progress in brain research · doi:10.1016/bs.pbr.2015.07.005 · Cited by 28 · see citing works
Self-citationNeuropeptide modulation of addiction: Focus on galanin
Genders, S. G., Scheller, K. J., & Djouma, E. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.06.021 · Cited by 27 · see citing works
Kai, Y., Li, Y., Sun, T., Yin, W., Mao, Y., Li, J., Xie, W., Chen, S., Wang, L., Li, J., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0152-4 · Cited by 26 · see citing works
The Convergent Neuroscience of Affective Pain and Substance Use Disorder
Pahng, A. R. (2021) · Alcohol research · doi:10.35946/arcr.v41.1.14 · Cited by 23 · see citing works
Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models
Havel, V., Kruegel, A. C., Bechand, B., McIntosh, S., Stallings, L. S., Hodges, A., Wulf, M. G., Nelson, M., Hunkele, A., Ansonoff, M. A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-51856-y · Cited by 22 · see citing works
Cannella, N., Ubaldi, M., Masi, A., Bramucci, M., Roberto, M., Bifone, A., & Ciccocioppo, R. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.05.014 · Cited by 22 · see citing works
Barattini, A. E., Montanari, C., Edwards, K. N., Edwards, S., Gilpin, N. W., & Pahng, A. R. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109512 · Cited by 20 · see citing works
Self-citationTobore, T. O. (2021) · Advances in Redox Research · doi:10.1016/j.arres.2021.100003 · Cited by 20 · see citing works
Insights into the Neurobiology of Craving in Opioid Use Disorder
Lueptow, L. M., Shashkova, E., Miller, M. G., Evans, C. J., & Cahill, C. M. (2020) · Current anesthesiology reports · doi:10.1007/s40140-020-00420-7 · Cited by 19 · see citing works
Mantsch, J. R. (2022) · Addiction Neuroscience · doi:10.1016/j.addicn.2022.100038 · Cited by 19 · see citing works
Marchette, R. C. N., Carlson, E. R., Said, N., Koob, G. F., & Vendruscolo, L. F. (2022) · Addiction Neuroscience · doi:10.1016/j.addicn.2022.100057 · Cited by 18 · see citing works
Self-citationMcFalls, A. J., Imperio, C. G., Bixler, G. V., Freeman, W. M., Grigson, P. S., & Vrana, K. E. (2015) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2015.11.009 · Cited by 17 · see citing works
Joshi, D., Puaud, M., Fouyssac, M., Belin‐Rauscent, A., Everitt, B. J., & Belin, D. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14889 · Cited by 18 · see citing works
Measuring Pain Avoidance‐Like Behavior in Drug‐Dependent Rats
Pahng, A. R., & Edwards, S. (2018) · Current Protocols in Neuroscience · doi:10.1002/cpns.53 · Cited by 17 · see citing works
Self-citationLee, C. H., George, O., & Kimbrough, A. (2020) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2020.172880 · Cited by 14 · see citing works
A conceptual framework for the intersection of hyperalgesia and hyperkatifeia in alcohol addiction
Koob, G. F., & Vendruscolo, L. F. (2025) · Alcohol · doi:10.1016/j.alcohol.2025.08.004 · Cited by 13 · see citing works
Self-citationNeurobehavioral and neuroprotector effects of caffeine in animal models
Villanueva‐García, D., Mota‐Rojas, D., Miranda-Cortés, A. E., Mora‐Medina, P., Hernández-Ávalos, I., Casas-Alvarado, A., Olmos-Hernández, A. S., & Martı́nez-Burnes, J. (2020) · Journal of Animal Behaviour and Biometeorology · doi:10.31893/jabb.20039 · Cited by 13 · see citing works
Galaj, E., Barrera, E. D., Persaud, K., Nisanov, R., Vashisht, A., Goldberg, H., Patel, N., Lenhard, H., You, Z., Gardner, E. L., et al. (2023) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyad060 · Cited by 13 · see citing works
Neuropeptide and cytokine regulation of pain in the context of substance use disorders
Delery, E., & Edwards, S. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108153 · Cited by 12 · see citing works
Self-citationThe Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction
Marchette, R. C. N., Vendruscolo, L. F., & Koob, G. F. (2025) · Current Addiction Reports · doi:10.1007/s40429-025-00618-x · Cited by 13 · see citing works
Self-citationRole of CRF1 receptor in post-incisional plasma extravasation and nociceptive responses in mice
Romero, A., García-Carmona, J. A., Laorden, M. L., & Puig, M. M. (2017) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2017.04.021 · Cited by 9 · see citing works
Drug addiction co-morbidity with alcohol: Neurobiological insights
McGinn, M. A., Pantazis, C. B., Tunstall, B. J., Marchette, R. C. N., Carlson, E. R., Said, N., Koob, G. F., & Vendruscolo, L. F. (2021) · International review of neurobiology · doi:10.1016/bs.irn.2020.11.002 · Cited by 9 · see citing works
Self-citationCold nociception as a measure of hyperalgesia during spontaneous heroin withdrawal in mice
Hastings, L., Frye, E. V., Carlson, E. R., Chuong, V., Matthews, A. N., Koob, G. F., Vendruscolo, L. F., & Marchette, R. C. N. (2023) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2023.173694 · Cited by 8 · see citing works
Self-citationSex‐specific biobehavioral regulation of persistent inflammatory pain by alcohol
Cucinello‐Ragland, J. A., Alrashed, N. H., Lee, S., Davis, E. C., Edwards, K. N., & Edwards, S. (2023) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.15104 · Cited by 7 · see citing works
Self-citationSeeliger, C., Lippold, J. V., & Reuter, M. (2019) · Neuropsychobiology · doi:10.1159/000504227 · Cited by 7 · see citing works
Therapies in early development for the treatment of opiate addiction
Rodríguez‐Arias, M., Aguilar, M. A., & Miñarro, J. (2015) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2015.1086746 · Cited by 7 · see citing works
Schneider, P., Goldbaum, D., Agarwal, A., Taylor, A., Sundberg, P., Gardner, E. L., Ranaldi, R., You, Z., & Galaj, E. (2024) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2024.173931 · Cited by 5 · see citing works
Barattini, A. E., Gilpin, N. W., & Pahng, A. R. (2024) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2024.173890 · Cited by 5 · see citing works
Chen, Y., Xiao, T., & Kimbrough, A. (2024) · Psychopharmacology · doi:10.1007/s00213-024-06739-x · Cited by 7 · see citing works
Distinct Amygdala Neuronal Populations Control Opioid Use and Withdrawal in Mice
Tortorelli, L. S., Oo, H. Z., Hahn, S., Álvarez-Bagnarol, Y., Carrasquillo, Y., & Vendruscolo, L. F. (2025) · Biological Psychiatry · doi:10.1016/j.biopsych.2025.08.021 · Cited by 3 · see citing works
Self-citationOrtiz, A., Onge, C. M. S., & Banks, M. L. (2025) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/j.jpet.2025.103717 · Cited by 3 · see citing works
Intermittent Extended Access Rodent Models of Compulsive Eating
Zorrilla, E. P., Kreisler, A. D., & Bagsic, S. R. S. (2020) · Neuromethods · doi:10.1007/978-1-0716-0924-8_8 · Cited by 3 · see citing works
Koob, G. F., Arends, M. A., McCracken, M. L., & Moal, M. L. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816863-9.00001-7 · Cited by 3 · see citing works
Self-citationNeurobiological theories of addiction
Koob, G. F., Arends, M. A., McCracken, M. L., & Moal, M. L. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816863-9.00003-0 · Cited by 3 · see citing works
Self-citationBrouillette, A. E., & Edwards, S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-26504-4.00018-1 · Cited by 1 · see citing works
Self-citationKoob, G. F., Arends, M. A., McCracken, M. L., & Moal, M. L. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-816988-9.00001-1 · Cited by 2 · see citing works
Self-citationCorticotropin-Releasing Factor Signaling at the Intersection of Pain and Opioid Addiction
McGinn, M. A., & Edwards, S. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800213-1.00083-3
Self-citationRole of Stress-Associated Signaling in Addiction
Doncheck, E. M., & Mantsch, J. R. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-812202-0.00011-7
Motivating Change in Addiction via Modulation of the Dark Side
Koob, G. F. (2018) · Nebraska Symposium on Motivation/The Nebraska symposium on motivation · doi:10.1007/978-3-319-96920-6_1
Self-citationAlsharari, S. D., Alameen, A. A., Aldafiri, F. S., Ali, Y. S., Alshammari, M. A., Sari, Y., & Damaj, M. (2024) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2024.07.006
Plasil, S. L., Tieu, L., Qian, C., Taylor, N., Sneddon, E. A., Carrette, L. L. G., Brennan, M., Morgan, A., Othman, D. N., Bai, K., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.14.725258
Plasil, S. L., Tieu, L., Qian, C., Taylor, N., Coe, S., Sneddon, E. A., Carrette, L. L. G., Brennan, M., Morgan, A. A., Othman, D. N., et al. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.111197
- Authors
- Park, P. E., Schlosburg, J. E., Vendruscolo, L. F., Schulteis, G., Edwards, S., & Koob, G. F.
- Affiliations
- Scripps Research Institute (US)
- University of California San Diego (US)
- Corresponding author
- Edwards, Scott
- Venue
- Addiction Biology
- Publisher
- Wiley
- Published
- 2013-12-13
- Volume
- 20
- Issue
- 2
- Pages
- 275-284
- ISSN
- 1355-6215 (ISSN-L)
- 1369-1600
- PMC
- PMC4057367
- OpenAlex
- W1891678001
- Cited by
- 69
- References
- 66
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 9 · 2019: 9 · 2018: 9 · 2017: 3 · 2016: 4 · 2015: 5
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Addiction Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DA004043, DA007315, AA007456, AA020839)
- U.S. Department of Veterans Affairs
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- heroin, opioid withdrawal, hyperalgesia, mechanical hypersensitivity, heroin self-administration, clonidine, norepinephrine, corticotropin-releasing factor, opioid-induced hyperalgesia, pain sensitization
- MeSH terms
- CRF Receptor, Type 1, Adrenergic beta-Antagonists, Animals, Behavior, Animal, Clonidine, Heroin, Heroin Dependence, Hyperalgesia, Narcotics, Prazosin, Propranolol, Pyrimidines, Self Administration, Receptors, Corticotropin-Releasing Hormone, Rats, Adrenergic alpha-2 Receptor Agonists, Adrenergic alpha-1 Receptor Antagonists, Drug-Seeking Behavior
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
