Sensitized brain response to acute pain in patients using prescription opiates for chronic pain: a pilot study
Open accessAbstract
Background Chronic opiate use leads to a sensitized behavioral response to acute pain, which in turn, leads to escalating doses of opiates. This study was designed to test the hypothesis that chronic opiate usage is also associated with a sensitized neurobiological response to acute pain in individuals that have used prescription opiates for 6 or more months.Methods Fourteen patients with non-alcoholic chronic pancreatitis that have been taking prescription opiates for 6 or more months and 14 gender matched, non-opiate using controls were enrolled. Functional neuroimaging data was acquired while participants received blocks of thermal stimulation to their wrist (individually-tailored to their pain threshold).Results Self-reported pain was significantly greater in opiate using patients (3.4 ± 3.4) than controls (0.2 ± 0.8: Brief Pain Inventory p < 0.005), however no significant difference between groups was observed in the individually-tailored pain thresholds. Opiate using patients evidenced a significantly greater response to pain than controls in two established nodes of the "Pain Matrix": somatosensory cortex (p FWE≤0.001) and anterior cingulate cortex (p ≤ 0.01). This response was positively correlated with prescribed morphine equivalent dosages (average: 133.5 ± 94.8 mg/day).Conclusion The findings suggest that in chronic pancreatitis patients, a dose of opiates that normalizes their behavioral response to acute pain is associated with an amplified neural response to acute pain. Further longitudinal studies are needed to determine if this neural sensitization hastens a behavioral tolerance to opiates or the development of an opioid use disorder.
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?
A single TMS pulse raises BOLD signal near the coil and in monosynaptic target regions.
“a single pulse of TMS induces an elevation in the BOLD signal in the vicinity of the TMS coil and in monosynaptic target regions [37,38].”
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
Dissociable intrinsic connectivity networks for salience processing and executive control
Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., Reiss, A. L., & Greicius, M. D. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5587-06.2007 · Cited by 7,426 · see citing works
Pain assessment: global use of the Brief Pain Inventory.
Cs, C., & Km, R. (1994) · PubMed · Cited by 5,178 · see citing works
<i>Conn</i> : A Functional Connectivity Toolbox for Correlated and Anticorrelated Brain Networks
Whitfield-Gabrieli, S., & Nieto-Castanon, A. (2012) · Brain Connectivity · doi:10.1089/brain.2012.0073 · Cited by 4,885 · see citing works
A component based noise correction method (CompCor) for BOLD and perfusion based fMRI
Behzadi, Y., Restom, K., Liau, J., & Liu, T. T. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.04.042 · Cited by 4,502 · see citing works
Human brain mechanisms of pain perception and regulation in health and disease
Apkarian, A. V., Bushnell, M. C., Treede, R., & Zubieta, J. (2005) · European Journal of Pain · doi:10.1016/j.ejpain.2004.11.001 · Cited by 3,126 · see citing works
Pain Affect Encoded in Human Anterior Cingulate But Not Somatosensory Cortex
Rainville, P., Duncan, G. H., Price, D. D., Carrier, B., & Bushnell, M. C. (1997) · Science · doi:10.1126/science.277.5328.968 · Cited by 2,629 · cited 1× · see citing works
“Activity in these regions is associated with motivational-affective processing of pain and tracks the unpleasantness of the stimulus (Apkarian et al., 2005; Price, 2000; Rainville et al., 1997).”
BackgroundIncreases in drug and opioid-involved overdose deaths – United States, 2010-2015
Rudd, R. A., Seth, P., David, F., & Scholl, L. (2016) · MMWR. Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm655051e1 · Cited by 2,194 · see citing works
Psychological and neural mechanisms of the affective dimension of pain
Price, D. D. (2000) · Science · doi:10.1126/science.288.5472.1769 · Cited by 2,092 · see citing works
An fMRI-Based Neurologic Signature of Physical Pain
Wager, T. D., Atlas, L. Y., Lindquist, M. A., Roy, M., Woo, C.-W., & Kross, E. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1204471 · Cited by 1,597 · see citing works
Opioid Abuse in Chronic Pain — Misconceptions and Mitigation Strategies
Volkow, N. D., & McLellan, A. T. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1507771 · Cited by 1,323 · 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
Rates of opioid misuse, abuse, and addiction in chronic pain
Vowles, K. E., McEntee, M. L., Julnes, P. S., Frohe, T. M., Ney, J. P., & van der Goes, D. N. (2015) · Pain · doi:10.1097/01.j.pain.0000460357.01998.f1 · Cited by 1,178 · see citing works
A Comprehensive Review of Opioid-Induced Hyperalgesia
Lee, M. O. (2011) · Pain Physician · doi:10.36076/ppj.2011/14/145 · Cited by 1,122 · see citing works
Vital signs: changes in opioid prescribing in the United States, 2006-2015.
Guy, G. P., Zhang, K., Bohm, M. K., Losby, J., Lewis, B., Young, R., Murphy, L. B., & Dowell, D. (2017) · MMWR. Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6626a4 · Cited by 1,117 · see citing works
Pain and the Neuromatrix in the Brain
Melzack, R. (2001) · Journal of Dental Education · doi:10.1002/j.0022-0337.2001.65.12.tb03497.x · Cited by 897 · see citing works
Endoscopic versus Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis
Cahen, D. L., Gouma, D. J., Nio, C. Y., Rauws, E. A., Boermeester, M. A., Busch, O. R., Stoker, J., Laméris, J. S., Dijkgraaf, M. G. W., Huibregtse, K., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa060610 · Cited by 845 · see citing works
Development and validation of the Current Opioid Misuse Measure
Butler, S. F., Budman, S. H., Fernandez, K. C., Houle, B., Benoit, C., Katz, N., & Jamison, R. N. (2007) · Pain · doi:10.1016/j.pain.2007.01.014 · Cited by 651 · see citing works
Endogenous 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
Kleeff, J. H., Whitcomb, D. C., Shimosegawa, T., Esposito, I., Lerch, M. M., Gress, T. M., Mayerle, J. V., Drewes, A. M., Rebours, V., Akisik, F. M., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.60 · Cited by 497 · see citing works
Rösch, T., Daniel, S., Scholz, M., et al. (2002) · Endoscopy · doi:10.1055/s-2002-34256 · Cited by 457 · see citing works
Kucyi, A., Moayedi, M., Weissman-Fogel, I., Goldberg, M. B., Freeman, B. V., Tenenbaum, H. C., & Davis, K. D. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.5055-13.2014 · Cited by 396 · see citing works
Alterations in brain structure and functional connectivity in prescription opioid-dependent patients
Upadhyay, J., Maleki, N., Potter, J. S., Elman, I., Rudrauf, D., Knudsen, J., Wallin, D. J., Pendse, G., McDonald, L., Griffin, M. L., et al. (2010) · Brain · doi:10.1093/brain/awq138 · Cited by 394 · see citing works
Opioid-induced hyperalgesia: Cellular and molecular mechanisms
Roeckel, L.-A., Coz, G.-M. L., Gavériaux‐Ruff, C., & Simonin, F. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.06.029 · Cited by 389 · see citing works
Zeidan, F., Emerson, N. M., Farris, S. R., Ray, J. N., Jung, Y., McHaffie, J. G., & Coghill, R. C. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2542-15.2015 · Cited by 369 · see citing works
Vanderah, T. W., Suenaga, N. M. H., Ossipov, M. H., Malan, T. P., Lai, J. Y., & Porreca, F. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-01-00279.2001 · Cited by 335 · see citing works
The impact of T1 versus EPI spatial normalization templates for fMRI data analyses
Calhoun, V. D., Wager, T. D., Krishnan, A., Rosch, K. S., Seymour, K. E., Nebel, M. B., Mostofsky, S. H., Nyalakanai, P., & Kiehl, K. A. (2017) · Human Brain Mapping · doi:10.1002/hbm.23737 · Cited by 325 · see citing works
Common brain mechanisms of chronic pain and addiction
Elman, I., & Borsook, D. (2016) · Neuron · doi:10.1016/j.neuron.2015.11.027 · Cited by 303 · see citing works
Use and misuse of opioids in chronic pain
Volkow, N., Benveniste, H., & McLellan, A. T. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-011817-044739 · Cited by 279 · see citing works
Mayer, E. A., Berman, S. M., Suyenobu, B. Y., Labus, J. S., Mandelkern, M. A., Naliboff, B. D., & Chang, L. (2005) · Pain · doi:10.1016/j.pain.2005.03.023 · Cited by 275 · 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
Underlying mechanisms of pronociceptive consequences of prolonged morphine exposure
Ossipov, M. H., Lai, J. Y., King, T. E., Vanderah, T. W., & Porreca, F. (2005) · Biopolymers · doi:10.1002/bip.20254 · Cited by 257 · see citing works
Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensity
Kong, J., White, N. S., Kwong, K. K., Vangel, M. G., Rosman, I. S., Gracely, R. H., & Gollub, R. L. (2006) · Human Brain Mapping · doi:10.1002/hbm.20213 · Cited by 256 · see citing works
Induction of Synaptic Long-Term Potentiation After Opioid Withdrawal
Drdla-Schutting, R., Gassner, M., Gingl, E., & Sandkühler, J. (2009) · Science · doi:10.1126/science.1171759 · Cited by 216 · see citing works
Brain Circuits Encoding Reward from Pain Relief
Navratilova, E., Atcherley, C. W., & Porreca, F. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.09.003 · Cited by 202 · see citing works
A new human experimental pain model
Petersen, K. L., & Rowbotham, M. C. (1999) · Neuroreport · doi:10.1097/00001756-199905140-00022 · Cited by 198 · see citing works
Pain in chronic pancreatitis: the role of neuropathic pain mechanisms
Drewes, A. M., Krarup, A. L., Detlefsen, S., Malmstrøm, M. L., Dimcevski, G. G., & Funch-Jensen, P. M. (2008) · Gut · doi:10.1136/gut.2007.146621 · Cited by 184 · see citing works
Modulation of pain, nociception, and analgesia by the brain reward center
Mitsi, V., & Zachariou, V. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.05.017 · Cited by 168 · see citing works
High opiate receptor binding potential in the human lateral pain system
Baumgärtner, U., Buchholz, H., Bellosevich, A., Magerl, W., Siessmeier, T., Rolke, R., Höhnemann, S., Piel, M., Rösch, F., Wester, H., et al. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.10.033 · Cited by 167 · see citing works
Further evidence validating adjuvant arthritis as an experimental model of chronic pain in the rat
Colpaert, F. C., Meert, T. F., Witte, P. D., & Schmitt, P. (1982) · Life Sciences · doi:10.1016/0024-3205(82)90402-7 · Cited by 164 · see citing works
Pain in Chronic Pancreatitis: The Role of Reorganization in the Central Nervous System
Dimcevski, G. G., Sami, S. A. K., Funch-Jensen, P. M., Pera, D. L., Valeriani, M., Arendt‐Nielsen, L., & Drewes, A. M. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.01.037 · Cited by 161 · see citing works
Opioid-Induced Long-Term Potentiation in the Spinal Cord Is a Presynaptic Event
Zhou, H.-Y., Chen, S.-R., Chen, H., & Pan, H. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5857-09.2010 · Cited by 140 · see citing works
Opiate self-administration as a measure of chronic nociceptive pain in arthritic rats
Colpaert, F. C., Tarayre, J. P., Aliaga, M., Slot, L. A. B., Attal, N., & Koek, W. (2001) · Pain · doi:10.1016/s0304-3959(00)00413-9 · Cited by 139 · see citing works
Opioidergic activation in the medial pain system after heat pain
Sprenger, T., Valet, M., Boecker, H., Henriksen, G., Spilker, M. E., Willoch, F., Wagner, K. J., Wester, H. J., & Tölle, T. R. (2006) · Pain · doi:10.1016/j.pain.2006.01.003 · Cited by 119 · see citing works
Brain mediators of the effects of noxious heat on pain
Atlas, L. Y., Lindquist, M. A., Bolger, N. P., & Wager, T. D. (2014) · Pain · doi:10.1016/j.pain.2014.05.015 · Cited by 112 · see citing works
Fregni, F., Potvin, K., Silva, D., Wang, X., Lenkinski, R. E., Freedman, S. D., & Pascual‐Leone, Á. (2010) · European Journal of Pain · doi:10.1016/j.ejpain.2010.08.002 · Cited by 107 · see citing works
Cerebral interactions of pain and reward and their relevance for chronic pain
Becker, S., Gandhi, W., & Schweinhardt, P. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.03.013 · Cited by 103 · see citing works
Differential effect of opioids in patients with chronic pancreatitis: An experimental pain study
Staahl, C., Dimcevski, G. G., Andersen, S. D., et al. (2006) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520601014414 · Cited by 98 · see citing works
Tănăsescu, R., Cottam, W. J., Condon, L. A., Tench, C. R., & Auer, D. P. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.04.001 · Cited by 90 · see citing works
Frøkjær, J. B., Bouwense, S. A. W., Olesen, S. S., Lundager, F. H., Eskildsen, S. F., van Goor, H., Wilder‐Smith, O. H. G., & Drewes, A. M. (2011) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2011.11.024 · Cited by 89 · see citing works
Flodin, P., Martinsen, S., Altawil, R., Waldheim, E., Lampa, J., Kosek, E., & Fransson, P. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00107 · Cited by 89 · see citing works
Brainstem involvement in the initial response to pain
Petrović, P., Petersson, K. M., Hansson, P. T., & Ingvar, M. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.01.046 · Cited by 87 · see citing works
The pain of chronic pancreatitis: a persistent clinical challenge
Goulden, M. R. (2013) · British Journal of Pain · doi:10.1177/2049463713479230 · Cited by 74 · see citing works
Vogt, B. A., Watanabe, H., Grootoonk, S., & Jones, A. K. P. (1995) · Human Brain Mapping · doi:10.1002/hbm.460030102 · Cited by 71 · see citing works
Altered central pain processing after pancreatic surgery for chronic pancreatitis
Bouwense, S. A. W., Ali, U. A., ten Broek, R. P. G., Issa, Y., van Eijck, C. H. J., Wilder‐Smith, O. H. G., & van Goor, H. (2013) · British journal of surgery · doi:10.1002/bjs.9322 · Cited by 71 · see citing works
Pain and opioid use in chronic pancreatitis
Nusrat, S., Yadav, D., & Bielefeldt, K. (2012) · Pancreas · doi:10.1097/mpa.0b013e318224056f · Cited by 67 · see citing works
Ozaki, S., Narita, M., Narita, M., Ozaki, M., Khotib, J., & Suzuki, T. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02272.x · Cited by 66 · see citing works
Morphine self-administration in the rat during adjuvant-induced arthritis
Lyness, W. H., Smith, F. L., Heavner, J. E., Iacono, C. U., & Garvin, R. D. (1989) · Life Sciences · doi:10.1016/0024-3205(89)90062-3 · Cited by 66 · see citing works
Rivat, C., Vera–Portocarrero, L. P., Ibrahim, M. M., Mata, H. P., Stagg, N. J., Felice, M. D., Porreca, F., & Malan, T. P. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06616.x · Cited by 65 · see citing works
Wu, L., Huang, X., & Sun, L. (2015) · Journal of Clinical Anesthesia · doi:10.1016/j.jclinane.2015.03.020 · Cited by 63 · see citing works
Dimcevski, G. G., Staahl, C., Andersen, S. D., Thorsgaard, N., Funch-Jensen, P. M., Arendt‐Nielsen, L., & Drewes, A. M. (2007) · Pancreas · doi:10.1097/mpa.0b013e31805c1762 · Cited by 57 · see citing works
Unravelling the Mystery of Pain, Suffering, and Relief With Brain Imaging
Lee, M., & Tracey, I. (2010) · Current Pain and Headache Reports · doi:10.1007/s11916-010-0103-0 · Cited by 55 · see citing works
Hou, Y.-Y., Cai, Y.-Q., & Pan, Z. Z. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3453-14.2015 · Cited by 51 · see citing works
Zhang, Z., Tao, W., Hou, Y.-Y., Wang, W., Lu, Y.-G., & Pan, Z. Z. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.77 · Cited by 49 · see citing works
Pain and motives for use among non‐treatment seeking individuals with prescription opioid dependence
Barth, K. S., Maria, M. M. M., Lawson, K. M., Shaftman, S. R., Brady, K. T., & Back, S. E. (2013) · American Journal on Addictions · doi:10.1111/j.1521-0391.2013.12038.x · Cited by 46 · see citing works
Self-citationBrain mechanisms supporting violated expectations of pain
Zeidan, F., Lobanov, O. V., Kraft, R. A., & Coghill, R. C. (2015) · Pain · doi:10.1097/j.pain.0000000000000231 · Cited by 41 · see citing works
Sanna, M. D., Ghelardini, C., & Galeotti, N. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.06.007 · Cited by 39 · see citing works
Analgesics as reinforcers with chronic pain: Evidence from operant studies
Ewan, E. E., & Martin, T. J. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.08.018 · Cited by 36 · see citing works
Hypoalgesia to experimental visceral and somatic stimulation in painful chronic pancreatitis
Dimcevski, G. G., Schipper, K., Tage‐Jensen, U., Funch-Jensen, P. M., Krarup, A. L., Toft, E. S., Thorsgaard, N., Arendt‐Nielsen, L., & Drewes, A. M. (2006) · European Journal of Gastroenterology & Hepatology · doi:10.1097/01.meg.0000223903.70492.c5 · Cited by 35 · see citing works
Anticipation and violated expectation of pain are influenced by trait rumination: An fMRI study
Kökönyei, G., Galambos, A., Édes, A. E., Kocsel, N., Szabó, E., Pap, D., Kozák, L. R., Bagdy, G., & Juhász, G. (2018) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-018-0644-y · Cited by 24 · see citing works
Massive Modulation of Brain Areas After Mechanical Pain Stimulation: A Time-Resolved fMRI Study
Cauda, F., Costa, T., Diano, M., Sacco, K., Duca, S., Geminiani, G. C., & Torta, D. M. E. (2013) · Cerebral Cortex · doi:10.1093/cercor/bht153 · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mahoney, J. J., Hanlon, C. A., Marshalek, P. J., Rezai, A. R., & Krinke, L. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.117149 · Cited by 121 · see citing works
Self-citation
- Authors
- Dowdle, L. T., Borckardt, J. J., Back, S. E., Morgan, K., Adams, D., Madan, A., Balliet, W., & Hanlon, C. A.
- Affiliations
- Medical University of South Carolina (US)
- Houston Methodist (US)
- Corresponding author
- Hanlon, Colleen A.
- ORCID
- Venue
- Drug and Alcohol Dependence
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 200
- Pages
- 6-13
- ISSN
- 0376-8716 (ISSN-L)
- PMC
- PMC6914256
- OpenAlex
- W2940764370
- Cited by
- 8
- References
- 70
- Citations by year
- 2025: 1 · 2024: 3 · 2022: 1 · 2021: 2 · 2020: 1
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Drug and Alcohol Dependence (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Keywords
- chronic pain, acute pain, pain matrix, neural sensitization, chronic pancreatitis, somatosensory cortex, anterior cingulate cortex, morphine milligram equivalents, opioid tolerance, opioid use disorder
- MeSH terms
- Adult, Analgesics, Opioid, Brain, Drug Tolerance, Female, Humans, Male, Middle Aged, Morphine, Opioid-Related Disorders, Pain Measurement, Pancreatitis, Pilot Projects, Substance-Related Disorders, Chronic Pain, Acute Pain
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
