Originally from Connecticut, I graduated from the University of Connecticut in 2005 with a BS in Physiology and Neurobiology. I then moved to North Carolina and completed my PhD in 2011 under the mentorship of Dr. Robert Coghill at Wake Forest School of Medicine. During my graduate career, I conducted research on the temporal aspect of pain processing (how noxious thermal stimuli are processed over time by the nervous system) using both psychophysics and fMRI. Primarily, my dissertation focused on elucidating the mechanisms supporting offset analgesia, a pain phenomenon that exemplifies how the offset of pain is temporally enhanced by the nervous system at the end of a noxious stimulus.

I am currently a postdoctoral fellow in the Stanford Systems Neuroscience and Pain Lab under the mentorship of Dr. Sean Mackey. Several of my research projects are conducted as part of the MAPP study (Multidisciplinary Approach to the Study of Chronic Pelvic Pain), a collaborative multi-site project investigating chronic pelvic pain.

Presently, for my advanced postdoctoral training, I am working on a NIH NIDA funded research study investigating central nervous system activity and reward processing in fibromyalgia using fMRI.

Some of my additional research interests include plasticity of the central nervous system, opioid-induced hyperalgesia, and complex regional pain syndrome. One of my broad goals is to identify specific biomarkers using neuroimaging techniques (e.g., structural and functional MRI) and pain psychophysics to help classify subsets of chronic pain conditions that would be potentially more responsive to various therapies. Also, I would like to advance the understanding of how central nervous system plasticity contributes to chronic pain.

Aside from research I enjoy playing tennis, skiing, hiking and traveling. I also rely on barre classes, yoga and running for stress relief!

Honors & Awards

  • NIH Pathway to Independence Award (K99), NIH NIDA (2015 - 2016)
  • NIH Loan Repayment Program in Clinical Research, NIH (2014 - 2016)
  • International Association for the Study of Pain Travel Award, IASP (2014)
  • NIH Institutional Postdoctoral Anesthesia Training Program in Biomedical Research (T32), NIH (2013 - 2015)
  • NIH Individual Predoctoral Ruth L. Kirschstein National Research Service Award (F31), NIH NIDA (2010 - 2012)
  • American Pain Society Young Investigator Travel Award, APS (2009, 2010, 2013, 2014)
  • NIH Institutional Predoctoral Neurobiology and Anatomy Sensory Training Grant (T31), NIH (2007 - 2009)

Boards, Advisory Committees, Professional Organizations

  • Member, Human Brain Mapping (2011 - Present)
  • Member, American Pain Society (2008 - Present)
  • Member, International Association for the Study of Pain (2007 - Present)
  • Member, Society for Neuroscience (2006 - Present)
  • Member, Student Councilor, Western North Carolina Chapter of the Society for Neuroscience (2005 - 2011)

Professional Education

  • Doctor of Philosophy, Wake Forest University (2011)
  • Bachelor of Science, University of Connecticut (2005)

Stanford Advisors

Community and International Work

  • Reviewer (ad-hoc)

    Ongoing Project


    Opportunities for Student Involvement


  • Women in Science and Engineering (WISE)

    Ongoing Project


    Opportunities for Student Involvement


  • Stanford Postdoctoral Association - CoChair 2014

    Ongoing Project


    Opportunities for Student Involvement


  • Stanford Postdoc Initiative Fund (SPIF)

    Ongoing Project


    Opportunities for Student Involvement


Current Research and Scholarly Interests

Although opioids are widely prescribed for chronic pain due to fibromyalgia (FM), the effects of opioid medications on the activity of the central nervous system (CNS) and on reward behavior and clinical outcomes have not been determined for this indication. Current evidence strongly suggests that altered activity in the brain and spinal cord contributes to the chronicity of FM symptoms, and opioids are known to produce similar changes in CNS activity. Thus, my central hypothesis is that opioids exacerbate existing alterations in pain and reward processes in the CNS in individuals with FM. To test this hypothesis, I am conducting clinical neuroimaging research projects under the guidance of expert mentors, advisors and collaborators at Stanford University (Drs. Sean Mackey, Brian Knutson, Jodie Trafton, and Gary Glover).

As part of my K99 mentored training in research, I will conduct a clinical research study using brain and spinal cord functional magnetic resonance imaging (fMRI) to measure differences between individuals with FM who take opioids and individuals with FM who do not. My Aim 1 will determine the effect of opioids on levels of pain and spinal cord activity in FM. My Aim 2 will determine the effect of opioids on the brain's reward systems and reward behavior in FM.

During the later R00 independent phase of my research (Aim 3),I will conduct a longitudinal clinical study of individuals with FM, both opioid-dependent and opioid-naïve, to determine changes in pain, symptoms, and CNS activity in FM over time.

Together, these projects will provide a more complete picture of the effects of opioid medications in FM and will fill the critical knowledge gaps of inherent risks of neurobiological changes and altered behavior and psychology that occur when prescribing opioids. Through my training in these research projects, I hope to successfully transition over the next few years to an independent R01-funded, faculty- level principal investigator and to achieve my long-term goal of establishing an independent research lab focused on neurological and behavioral alterations in chronic pain.

Graduate and Fellowship Programs

All Publications

  • Neuroimaging of Pain: Human Evidence and Clinical Relevance of Central Nervous System Processes and Modulation. Anesthesiology Martucci, K. T., Mackey, S. C. 2018; 128 (6): 1241–54


    Neuroimaging research has demonstrated definitive involvement of the central nervous system in the development, maintenance, and experience of chronic pain. Structural and functional neuroimaging has helped elucidate central nervous system contributors to chronic pain in humans. Neuroimaging of pain has provided a tool for increasing our understanding of how pharmacologic and psychologic therapies improve chronic pain. To date, findings from neuroimaging pain research have benefitted clinical practice by providing clinicians with an educational framework to discuss the biopsychosocial nature of pain with patients. Future advances in neuroimaging-based therapeutics (e.g., transcranial magnetic stimulation, real-time functional magnetic resonance imaging neurofeedback) may provide additional benefits for clinical practice. In the future, with standardization and validation, brain imaging could provide objective biomarkers of chronic pain, and guide treatment for personalized pain management. Similarly, brain-based biomarkers may provide an additional predictor of perioperative prognoses.

    View details for DOI 10.1097/ALN.0000000000002137

    View details for PubMedID 29494401

  • Altered prefrontal correlates of monetary anticipation and outcome in chronic pain. Pain Martucci, K. T., Borg, N., MacNiven, K. H., Knutson, B., Mackey, S. C. 2018


    Chronic pain may alter both affect- and value-related behaviors, which represents a potentially treatable aspect of chronic pain experience. Current understanding of how chronic pain influences the function of brain reward systems, however, is limited. Using a monetary incentive delay task and functional magnetic resonance imaging (fMRI), we measured neural correlates of reward anticipation and outcomes in female participants with the chronic pain condition of fibromyalgia (N = 17) and age-matched, pain-free, female controls (N = 15). We hypothesized that patients would demonstrate lower positive arousal, as well as altered reward anticipation and outcome activity within corticostriatal circuits implicated in reward processing. Patients demonstrated lower arousal ratings as compared with controls, but no group differences were observed for valence, positive arousal, or negative arousal ratings. Group fMRI analyses were conducted to determine predetermined region of interest, nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC), responses to potential gains, potential losses, reward outcomes, and punishment outcomes. Compared with controls, patients demonstrated similar, although slightly reduced, NAcc activity during gain anticipation. Conversely, patients demonstrated dramatically reduced mPFC activity during gain anticipation-possibly related to lower estimated reward probabilities. Further, patients demonstrated normal mPFC activity to reward outcomes, but dramatically heightened mPFC activity to no-loss (nonpunishment) outcomes. In parallel to NAcc and mPFC responses, patients demonstrated slightly reduced activity during reward anticipation in other brain regions, which included the ventral tegmental area, anterior cingulate cortex, and anterior insular cortex. Together, these results implicate altered corticostriatal processing of monetary rewards in chronic pain.

    View details for DOI 10.1097/j.pain.0000000000001232

    View details for PubMedID 29790868

  • Resting-state functional connectivity predicts longitudinal pain symptom change in urologic chronic pelvic pain syndrome: a MAPP network study. Pain Kutch, J. J., Labus, J. S., Harris, R. E., Martucci, K. T., Farmer, M. A., Fenske, S., Fling, C., Ichesco, E., Peltier, S., Petre, B., Guo, W., Hou, X., Stephens, A. J., Mullins, C., Clauw, D. J., Mackey, S. C., Apkarian, A. V., Landis, J. R., Mayer, E. A. 2017; 158 (6): 1069-1082


    Chronic pain symptoms often change over time, even in individuals who have had symptoms for years. Studying biological factors that predict trends in symptom change in chronic pain may uncover novel pathophysiological mechanisms and potential therapeutic targets. In this study, we investigated whether brain functional connectivity measures obtained from resting-state functional magnetic resonance imaging at baseline can predict longitudinal symptom change (3, 6, and 12 months after scan) in urologic chronic pelvic pain syndrome. We studied 52 individuals with urologic chronic pelvic pain syndrome (34 women, 18 men) who had baseline neuroimaging followed by symptom tracking every 2 weeks for 1 year as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. We found that brain functional connectivity can make a significant prediction of short-term (3 month) pain reduction with 73.1% accuracy (69.2% sensitivity and 75.0% precision). In addition, we found that the brain regions with greatest contribution to the classification were preferentially aligned with the left frontoparietal network. Resting-state functional magnetic resonance imaging measures seemed to be less informative about 6- or 12-month symptom change. Our study provides the first evidence that future trends in symptom change in patients in a state of chronic pain may be linked to functional connectivity within specific brain networks.

    View details for DOI 10.1097/j.pain.0000000000000886

    View details for PubMedID 28328579

  • Disentangling mood and pain: a commentary on 2 manuscripts. Pain Martucci, K. T. 2017; 158 (1): 4-5

    View details for PubMedID 27764037

  • Investigating the BOLD Spectral Power of the Intrinsic Connectivity Networks in Fibromyalgia Patients: A Resting-state fMRI Study Jarrahi, B., Martucci, K. T., Nilakantan, A. S., Mackey, S., IEEE IEEE. 2017: 497–500


    Recent advances in multivariate statistical analysis of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) have provided novel insights into the network organization of the human brain. Here, we applied group independent component analysis, a well-established approach for detecting brain intrinsic connectivity networks, to examine the spontaneous BOLD fluctuations in patients with fibromyalgia and healthy controls before and after exposure to a stressor. The BOLD spectral power characteristics of component time courses were calculated using the fast Fourier transform (FFT) algorithm, and group comparison was performed at six frequency bins between 0 and 0.24 Hz at 0.04 Hz intervals. Relative to controls, patients with fibromyalgia displayed significant BOLD spectral power differences in the default-mode, salience, and subcortical networks at the baseline level (PBon ferroni-corrected <; 0.05). Multivariate analysis of covariance (MANCOVA) further revealed significant effects of the cold water temperature, and pain rating on the spectral power of the sensorimotor, salience, and prefrontal networks, while the diagnosis of fibromyalgia influenced the BOLD spectral power of the salience and subcortical networks (PFDR-corrected <; 0.05). Since the BOLD spectral power reflects the degree of fluctuations within a network, future studies of the correlation between BOLD spectral power and pain processing can cast additional light on the nature of the central nervous system dysfunction in patients with chronic pain syndromes.

    View details for Web of Science ID 000427085300123

    View details for PubMedID 29059918

    View details for PubMedCentralID PMC5966014

  • Brain white matter changes associated with urological chronic pelvic pain syndrome: multisite neuroimaging from a MAPP case-control study PAIN Huang, L., Kutch, J. J., Ellingson, B. M., Martucci, K. T., Harris, R. E., Clauw, D. J., Mackey, S., Mayer, E. A., Schaeffer, A. J., Apkarian, A. V., Farmer, M. A. 2016; 157 (12): 2782-2791


    Clinical phenotyping of urological chronic pelvic pain syndromes (UCPPSs) in men and women have focused on end organ abnormalities to identify putative clinical subtypes. Initial evidence of abnormal brain function and structure in male pelvic pain has necessitated large-scale, multisite investigations into potential UCPPS brain biomarkers. We present the first evidence of regional white matter (axonal) abnormalities in men and women with UCPPS, compared with positive (irritable bowel syndrome, IBS) and healthy controls. Epidemiological and neuroimaging data were collected from participants with UCPPS (n = 52), IBS (n = 39), and healthy sex- and age-matched controls (n = 61). White matter microstructure, measured as fractional anisotropy (FA), was examined by diffusion tensor imaging. Group differences in regional FA positively correlated with pain severity, including segments of the right corticospinal tract and right anterior thalamic radiation. Increased corticospinal FA was specific and sensitive to UCPPS, positively correlated with pain severity, and reflected sensory (not affective) features of pain. Reduced anterior thalamic radiation FA distinguished patients with IBS from those with UCPPS and controls, suggesting greater microstructural divergence from normal tract organization. Findings confirm that regional white matter abnormalities characterize UCPPS and can distinguish between visceral diagnoses, suggesting that regional axonal microstructure is either altered with ongoing pain or predisposes its development.

    View details for DOI 10.1097/j.pain.0000000000000703

    View details for Web of Science ID 000388501400019

    View details for PubMedID 27842046

    View details for PubMedCentralID PMC5117992

  • Imaging Pain. Anesthesiology clinics Martucci, K. T., Mackey, S. C. 2016; 34 (2): 255-269


    The challenges and understanding of acute and chronic pain have been illuminated through the advancement of central neuroimaging. Through neuroimaging research, new technology and findings have allowed us to identify and understand the neural mechanisms contributing to chronic pain. Several regions of the brain are known to be of particular importance for the maintenance and amplification of chronic pain, and this knowledge provides novel targets for future research and treatment. This article reviews neuroimaging for the study of chronic pain, and in particular, the rapidly advancing and popular research tools of structural and functional MRI.

    View details for DOI 10.1016/j.anclin.2016.01.001

    View details for PubMedID 27208709

  • The posterior medial cortex in urologic chronic pelvic pain syndrome: detachment from default mode network-a resting-state study from the MAPP Research Network PAIN Martucci, K. T., Shirer, W. R., Bagarinao, E., Johnson, K. A., Farmer, M. A., Labus, J. S., Apkarian, A. V., Deutsch, G., Harris, R. E., Mayer, E. A., Clauw, D. J., Greicius, M. D., Mackey, S. C. 2015; 156 (9): 1755-1764
  • Brain White Matter Abnormalities in Female Interstitial Cystitis/Bladder Pain Syndrome: A MAPP Network Neuroimaging Study JOURNAL OF UROLOGY Farmer, M. A., Huang, L., Martucci, K., Yang, C. C., Maravilla, K. R., Harris, R. E., Clauw, D. J., Mackey, S., Ellingson, B. M., Mayer, E. A., Schaeffer, A. J., Apkarian, A. V. 2015; 194 (1): 118-126


    Several chronic pain conditions may be distinguished by condition specific brain anatomical and functional abnormalities on imaging, which are suggestive of underlying disease processes. We present what is to our knowledge the first characterization of interstitial cystitis/bladder pain syndrome associated white matter (axonal) abnormalities based on multicenter neuroimaging from the MAPP Research Network.We assessed 34 women with interstitial cystitis/bladder pain syndrome and 32 healthy controls using questionnaires on pain, mood and daily function. White matter microstructure was evaluated by diffusion tensor imaging to model directional water flow along axons or fractional anisotropy. Regions correlating with clinical parameters were further examined for gender and syndrome dependence.Women with interstitial cystitis/bladder pain syndrome showed numerous white matter abnormalities that correlated with pain severity, urinary symptoms and impaired quality of life. Interstitial cystitis/bladder pain syndrome was characterized by decreased fractional anisotropy in aspects of the right anterior thalamic radiation, the left forceps major and the right longitudinal fasciculus. Increased fractional anisotropy was detected in the right superior and bilateral inferior longitudinal fasciculi.To our knowledge we report the first characterization of brain white matter abnormalities in women with interstitial cystitis/bladder pain syndrome. Regional decreases and increases in white matter integrity across multiple axonal tracts were associated with symptom severity. Given that white matter abnormalities closely correlated with hallmark symptoms of interstitial cystitis/bladder pain syndrome, including bladder pain and urinary symptoms, brain anatomical alterations suggest that there are neuropathological contributions to chronic urological pelvic pain.

    View details for DOI 10.1016/j.juro.2015.02.082

    View details for Web of Science ID 000356012100034

    View details for PubMedID 25711200

  • Increased Brain Gray Matter in the Primary Somatosensory Cortex is Associated with Increased Pain and Mood Disturbance in Patients with Interstitial Cystitis/Painful Bladder Syndrome JOURNAL OF UROLOGY Kairys, A. E., Schmidt-Wilcke, T., Puiu, T., Ichesco, E., Labus, J. S., Martucci, K., Farmer, M. A., Ness, T. J., Deutsch, G., Mayer, E. A., Mackey, S., Apkarian, A. V., Maravilla, K., Clauw, D. J., Harris, R. E. 2015; 193 (1): 131-137


    Interstitial cystitis is a highly prevalent pain condition estimated to affect 3% to 6% of women in the United States. Emerging data suggest there are central neurobiological components to the etiology of this disease. We report the first brain structural imaging findings from the MAPP network with data on more than 300 participants.We used voxel based morphometry to determine whether human patients with chronic interstitial cystitis display changes in brain morphology compared to healthy controls. A total of 33 female patients with interstitial cystitis without comorbidities and 33 age and gender matched controls taken from the larger sample underwent structural magnetic resonance imaging at 5 MAPP sites across the United States.Compared to controls, females with interstitial cystitis displayed significant increased gray matter volume in several regions of the brain including the right primary somatosensory cortex, the superior parietal lobule bilaterally and the right supplementary motor area. Gray matter volume in the right primary somatosensory cortex was associated with greater pain, mood (anxiety) and urological symptoms. We explored these correlations in a linear regression model, and found independent effects of these 3 measures on primary somatosensory cortex gray matter volume, namely clinical pain (McGill pain sensory total), a measure of urgency and anxiety (HADS).These data support the notion that changes in somatosensory gray matter may have an important role in pain sensitivity as well as affective and sensory aspects of interstitial cystitis. Further studies are needed to confirm the generalizability of these findings to other pain conditions.

    View details for DOI 10.1016/j.juro.2014.08.042

    View details for Web of Science ID 000346171500033

    View details for PubMedID 25132239

  • Preliminary structural MRI based brain classification of chronic pelvic pain: A MAPP network study. Pain Bagarinao, E., Johnson, K. A., Martucci, K. T., Ichesco, E., Farmer, M. A., Labus, J., Ness, T. J., Harris, R., Deutsch, G., Apkarian, A. V., Mayer, E. A., Clauw, D. J., Mackey, S. 2014; 155 (12): 2502-2509


    Neuroimaging studies have shown that changes in brain morphology often accompany chronic pain conditions. However, brain biomarkers that are sensitive and specific to chronic pelvic pain (CPP) have not yet been adequately identified. Using data from the Trans-MAPP Research Network, we examined the changes in brain morphology associated with CPP. We used a multivariate pattern classification approach to detect these changes and to identify patterns that could be used to distinguish participants with CPP from age-matched healthy controls. In particular, we used a linear support vector machine (SVM) algorithm to differentiate gray matter images from the 2 groups. Regions of positive SVM weight included several regions within the primary somatosensory cortex, pre-supplementary motor area, hippocampus, and amygdala were identified as important drivers of the classification with 73% overall accuracy. Thus, we have identified a preliminary classifier based on brain structure that is able to predict the presence of CPP with a good degree of predictive power. Our regional findings suggest that in individuals with CPP, greater gray matter density may be found in the identified distributed brain regions, which are consistent with some previous investigations in visceral pain syndromes. Future studies are needed to improve upon our identified preliminary classifier with integration of additional variables and to assess whether the observed differences in brain structure are unique to CPP or generalizable to other chronic pain conditions.

    View details for DOI 10.1016/j.pain.2014.09.002

    View details for PubMedID 25242566

  • Neuroimaging chronic pain: what have we learned and where are we going? Future neurology Martucci, K. T., Ng, P., Mackey, S. 2014; 9 (6): 615-626


    Advances in neuroimaging have helped illuminate our understanding of how the brain works in the presence of chronic pain, which often persists with unknown etiology or after the painful stimulus has been removed and any wounds have healed. Neuroimaging has enabled us to make great progress in identifying many of the neural mechanisms that contribute to chronic pain, and to pinpoint the specific regions of the brain that are activated in the presence of chronic pain. It has provided us with a new perception of the nature of chronic pain in general, leading researchers to move toward a whole-brain approach to the study and treatment of chronic pain, and to develop novel technologies and analysis techniques, with real potential for developing new diagnostics and more effective therapies. We review the use of neuroimaging in the study of chronic pain, with particular emphasis on magnetic resonance imaging.

    View details for DOI 10.2217/FNL.14.57

    View details for PubMedID 28163658

    View details for PubMedCentralID PMC5289824

  • Alterations in resting state oscillations and connectivity in sensory and motor networks in women with interstitial cystitis/painful bladder syndrome. journal of urology Kilpatrick, L. A., Kutch, J. J., Tillisch, K., Naliboff, B. D., Labus, J. S., Jiang, Z., Farmer, M. A., Apkarian, A. V., Mackey, S., Martucci, K. T., Clauw, D. J., Harris, R. E., Deutsch, G., Ness, T. J., Yang, C. C., Maravilla, K., Mullins, C., Mayer, E. A. 2014; 192 (3): 947-955


    The pathophysiology of interstitial cystitis/painful bladder syndrome remains incompletely understood but is thought to involve central disturbance in the processing of pain and viscerosensory signals. We identified differences in brain activity and connectivity between female patients with interstitial cystitis/painful bladder syndrome and healthy controls to advance clinical phenotyping and treatment efforts for interstitial cystitis/painful bladder syndrome.We examined oscillation dynamics of intrinsic brain activity in a large sample of well phenotyped female patients with interstitial cystitis/painful bladder syndrome and female healthy controls. Data were collected during 10-minute resting functional magnetic resonance imaging as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network project. The blood oxygen level dependent signal was transformed to the frequency domain. Relative power was calculated for multiple frequency bands.Results demonstrated altered frequency distributions in viscerosensory (post insula), somatosensory (postcentral gyrus) and motor regions (anterior paracentral lobule, and medial and ventral supplementary motor areas) in patients with interstitial cystitis/painful bladder syndrome. Also, the anterior paracentral lobule, and medial and ventral supplementary motor areas showed increased functional connectivity to the midbrain (red nucleus) and cerebellum. This increased functional connectivity was greatest in patients who reported pain during bladder filling.Findings suggest that women with interstitial cystitis/painful bladder syndrome have a sensorimotor component to the pathological condition involving an alteration in intrinsic oscillations and connectivity in a cortico-cerebellar network previously associated with bladder function.

    View details for DOI 10.1016/j.juro.2014.03.093

    View details for PubMedID 24681331

  • Neural Correlates of Mindfulness Meditation-Related Anxiety Relief. Social cognitive and affective neuroscience Zeidan, F., Martucci, K. T., Kraft, R. A., McHaffie, J. G., Coghill, R. C. 2013


    Anxiety is the cognitive state related to the inability to control emotional responses to perceived threats. Anxiety is inversely related to brain activity associated with the cognitive regulation of emotions. Mindfulness meditation has been found to regulate anxiety. However, the brain mechanisms involved in meditation-related anxiety relief are largely unknown. We employed pulsed arterial spin labeling MRI to compare the effects of distraction in the form of attending to the breath (ATB) (before meditation training) to mindfulness meditation (after meditation training) on state anxiety across the same subjects. Fifteen healthy subjects, with no prior meditation experience, participated in 4 d of mindfulness meditation training. ATB did not reduce state anxiety, but state anxiety was significantly reduced in every session that subjects meditated. Meditation-related anxiety relief was associated with activation of the anterior cingulate cortex, ventromedial prefrontal cortex and anterior insula. Meditation-related activation in these regions exhibited a strong relationship to anxiety relief when compared to ATB. During meditation, those who exhibited greater default-related activity (i.e., posterior cingulate cortex) reported greater anxiety, possibly reflecting an inability to control self-referential thoughts. These findings provide evidence that mindfulness meditation attenuates anxiety through mechanisms involved in the regulation of self-referential thought processes.

    View details for DOI 10.1093/scan/nst041

    View details for PubMedID 23615765

  • Opioid-independent mechanisms supporting offset analgesia and temporal sharpening of nociceptive information PAIN Martucci, K. T., Eisenach, J. C., Tong, C., Coghill, R. C. 2012; 153 (6): 1232-1243


    The mechanisms supporting temporal processing of pain remain poorly understood. To determine the involvement of opioid mechanisms in temporal processing of pain, responses to dynamic noxious thermal stimuli and offset analgesia were assessed after administration of naloxone, a μ-opioid antagonist, and on a separate day, during and after intravenous administration of remifentanil, a μ-opioid agonist, in 19 healthy human volunteers. Multiple end points were sampled from real-time computerized visual analog scale ratings (VAS, 1 to 10) to assess thermal sensitivity, magnitude and duration of offset analgesia, and painful after sensations. It was hypothesized that the magnitude of offset analgesia would be reduced by direct opioid antagonism and during states of acute opioid-induced hypersensitivity (OIH), as well as diminished by the presence of exogenous opioids. Surprisingly, the magnitude of offset analgesia was not altered after naloxone administration, during remifentanil infusion, or after the termination of remifentanil infusion. Because thermal hyperalgesia was observed after both drugs, 8 of the original 19 subjects returned for an additional session without drug administration. Thermal hyperalgesia and increased magnitude of offset analgesia were observed across conditions of remifentanil, naloxone, and no drug within this subset analysis, indicating that repeated heat testing induced thermal hyperalgesia, which potentiated the magnitude of offset analgesia. Thus, it is concluded that the mechanisms subserving temporal processing of nociceptive information are largely opioid-independent, but that offset analgesia may be potentiated by heat-induced thermal hyperalgesia in a proportion of individuals.

    View details for DOI 10.1016/j.pain.2012.02.035

    View details for Web of Science ID 000304249100019

    View details for PubMedID 22503222

  • Differential effects of experimental central sensitization on the time-course and magnitude of offset analgesia PAIN Martucci, K. T., Yelle, M. D., Coghill, R. C. 2012; 153 (2): 463-472


    Pain perception is temporally altered during states of chronic pain and acute central sensitization; however, the mechanisms contributing to temporal processing of nociceptive information remain poorly understood. Offset analgesia is a phenomenon that reflects the presence of temporal contrast mechanisms for nociceptive information and can provide an end point to study temporal aspects of pain processing. In order to investigate whether offset analgesia is disrupted during sensitized states, 23 healthy volunteers provided real-time continuous visual analogue scale responses to noxious heat stimuli that evoke offset analgesia. Responses to these stimuli were evaluated during capsaicin-heat sensitization (45°C stimulus, capsaicin cream 0.1%) and heat-only sensitization (40°C stimulus, placebo cream). Capsaicin-heat sensitization produced significantly larger regions of secondary mechanical allodynia compared to heat-only sensitization. Although areas of mechanical allodynia were positively related to individual differences in heat pain sensitivity, this relationship was altered at later time points after capsaicin-heat sensitization. Heat hyperalgesia was observed in the secondary region following both capsaicin-heat and heat-only sensitization. Increased latencies to maximal offset analgesia and prolonged aftersensations were observed only in the primary regions directly treated by capsaicin-heat or heat alone. However, contrary to the hypothesis that offset analgesia would be reduced following capsaicin-heat sensitization, the magnitude of offset analgesia remained remarkably intact after both capsaicin-heat and heat-only sensitization in zones of both primary and secondary mechanical allodynia. These data indicate that offset analgesia is a robust phenomenon and engages mechanisms that interact minimally with those supporting acute central sensitization.

    View details for DOI 10.1016/j.pain.2011.11.010

    View details for Web of Science ID 000299319800029

    View details for PubMedID 22154333

  • Brain Mechanisms Supporting the Modulation of Pain by Mindfulness Meditation JOURNAL OF NEUROSCIENCE Zeidan, F., Martucci, K. T., Kraft, R. A., Gordon, N. S., McHaffie, J. G., Coghill, R. C. 2011; 31 (14): 5540-5548


    The subjective experience of one's environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a nonevaluative representation of sensory events. To better understand how meditation influences the sensory experience, we used arterial spin labeling functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After 4 d of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain unpleasantness by 57% and pain intensity ratings by 40% when compared to rest. A two-factor repeated-measures ANOVA was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contralateral primary somatosensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent input and executive-order brain areas. Together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information.

    View details for DOI 10.1523/JNEUROSCI.5791-10.2011

    View details for Web of Science ID 000289213500040

    View details for PubMedID 21471390

  • Regional Anesthesia Functional Implications Beyond the Anesthetized Nerve ANESTHESIOLOGY Martucci, K. T., Coghill, R. C. 2011; 114 (1): 21-23

    View details for Web of Science ID 000285542700009

    View details for PubMedID 21150575