Academic Appointments

Professional Education

  • Fellowship, Stanford University,, Psychoneuropharmacology of Pain (2008)
  • Fellowship, Arizona State University,, Psychoneuroimmunology of Pain (2006)
  • PhD, University of Tennessee,, Experimental Psychophysiology (2003)
  • BS, Maryville College,, Psychology (1998)

Research & Scholarship

Clinical Trials

  • Effects of Low Dose Naltrexone in Fibromyalgia Not Recruiting

    Low Dose Naltrexone (LDN) has been reported anecdotally to reduce the symptoms of Fibromyalgia, a Chronic Multisystem Illness. The drug may work by regulating natural pain-reducing systems. In this study, we will administer both LDN and placebo to a small group of individuals with Fibromyalgia and Gulf War Syndrome, both Chronic Multisymptom Illnesses, to assess the drug's efficacy in treating the condition.

    Stanford is currently not accepting patients for this trial.

    View full details

  • Study of T3 for the Treatment of Fibromyalgia Not Recruiting

    Determine if T3 - the active form of thyroid hormone - is beneficial in fibromyalgia. Determine the feasibility and promise of an appropriately powered future prospective randomized controlled study of using T3 (the active form of thyroid hormone) for the treatment of fibromyalgia. We specifically aim to assess the feasibility, cost, obstacles and promise of conducting a prospective controlled study in the future.

    Stanford is currently not accepting patients for this trial. For more information, please contact Rebecca McCue, (650) 724 - 0522.

    View full details


2013-14 Courses

Postdoctoral Advisees


Journal Articles

  • Complex regional pain syndrome is associated with structural abnormalities in pain-related regions of the human brain. journal of pain Barad, M. J., Ueno, T., Younger, J., Chatterjee, N., Mackey, S. 2014; 15 (2): 197-203


    Complex regional pain syndrome (CRPS) is a chronic condition that involves significant hyperalgesia of the affected limb, typically accompanied by localized autonomic abnormalities and frequently by motor dysfunction. Although central brain systems are thought to play a role in the development and maintenance of CRPS, these systems have not been well characterized. In this study, we used structural magnetic resonance imaging to characterize differences in gray matter volume between patients with right upper extremity CRPS and matched controls. Analyses were carried out using a whole brain voxel-based morphometry approach. The CRPS group showed decreased gray matter volume in several pain-affect regions, including the dorsal insula, left orbitofrontal cortex, and several aspects of the cingulate cortex. Greater gray matter volume in CRPS patients was seen in the bilateral dorsal putamen and right hypothalamus. Correlation analyses with self-reported pain were then performed on the CRPS group. Pain duration was associated with decreased gray matter in the left dorsolateral prefrontal cortex. Pain intensity was positively correlated with volume in the left posterior hippocampus and left amygdala, and negatively correlated with the bilateral dorsolateral prefrontal cortex. Our findings demonstrate that CRPS is associated with abnormal brain system morphology, particularly pain-related sensory, affect, motor, and autonomic systems.This paper presents structural changes in the brains of patients with CRPS, helping us differentiate CRPS from other chronic pain syndromes and furthering our understanding of this challenging disease.

    View details for DOI 10.1016/j.jpain.2013.10.011

    View details for PubMedID 24212070

  • A Pilot Functional MRI Study of the Effects of Prefrontal rTMS on Pain Perception PAIN MEDICINE Martin, L., Borckardt, J. J., Reeves, S. T., Frohman, H., Beam, W., Nahas, Z., Johnson, K., Younger, J., Madan, A., Patterson, D., George, M. 2013; 14 (7): 999-1009


    Repetitive transcranial magnetic stimulation (rTMS) has been shown to effectively treat depression, and its potential value in pain management is emphasized by recent studies. Transcranial magnetic stimulation (TMS)-evoked activity in the prefrontal cortex may be associated with corticolimbic inhibitory circuits capable of decreasing pain perception. The present exploratory pilot study used functional magnetic resonance imaging (fMRI) to examine the effects of left prefrontal rTMS on brain activity and pain perception.Twenty-three healthy adults with no history of depression or chronic pain underwent an 8-minute thermal pain protocol with fMRI before and after a single rTMS session. Participants received 15 minutes of either real (N = 12) or sham (N = 11) 10 Hz rTMS over the left prefrontal cortex (110% of resting motor threshold; 5 seconds on, 10 seconds off).TMS was associated with a 13.30% decrease in pain ratings, while sham was associated with an 8.61% decrease (P = 0.04). TMS was uniquely associated with increased activity in the posterior cingulate gyrus, precuneous, right superior frontal gyrus, right insula, and bilateral postcentral gyrus. Activity in the right superior prefrontal gyrus was negatively correlated with pain ratings (r = -0.65, P = 0.02) in the real TMS group.Findings suggest that prefrontal rTMS may be capable of activating inhibitory circuits involved with pain reduction.

    View details for DOI 10.1111/pme.12129

    View details for Web of Science ID 000330245100014

    View details for PubMedID 23647651

  • Perioperative Interventions to Reduce Chronic Postsurgical Pain JOURNAL OF RECONSTRUCTIVE MICROSURGERY Carroll, I., Hah, J., Mackey, S., Ottestad, E., Kong, J. T., Lahidji, S., Tawfik, V., Younger, J., Curtin, C. 2013; 29 (4): 213-222


    Approximately 10% of patients following a variety of surgeries develop chronic postsurgical pain. Reducing chronic postoperative pain is especially important to reconstructive surgeons because common operations such as breast and limb reconstruction have even higher risk for developing chronic postsurgical pain. Animal studies of posttraumatic nerve injury pain demonstrate that there is a critical time frame before and immediately after nerve injury in which specific interventions can reduce the incidence and intensity of chronic neuropathic pain behaviors-so called "preventative analgesia." In animal models, perineural local anesthetic, systemic intravenous local anesthetic, perineural clonidine, systemic gabapentin, systemic tricyclic antidepressants, and minocycline have each been shown to reduce pain behaviors days to weeks after treatment. The translation of this work to humans also suggests that brief perioperative interventions may protect patients from developing new chronic postsurgical pain. Recent clinical trial data show that there is an opportunity during the perioperative period to dramatically reduce the incidence and severity of chronic postsurgical pain. The surgeon, working with the anesthesiologist, has the ability to modify both early and chronic postoperative pain by implementing an evidence-based preventative analgesia plan.

    View details for DOI 10.1055/s-0032-1329921

    View details for Web of Science ID 000317597000001

    View details for PubMedID 23463498

  • Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology JOURNAL OF TRANSLATIONAL MEDICINE Stringer, E. A., Baker, K. S., Carroll, I. R., Montoya, J. G., Chu, L., Maecker, H. T., Younger, J. W. 2013; 11


    Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity.Therefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days.Self-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy.Our results support the role of cytokines in the pathophysiology of CFS.

    View details for DOI 10.1186/1479-5876-11-93

    View details for Web of Science ID 000318117400001

    View details for PubMedID 23570606

  • Low-Dose Naltrexone for the Treatment of Fibromyalgia ARTHRITIS AND RHEUMATISM Younger, J., Noor, N., McCue, R., Mackey, S. 2013; 65 (2): 529-538


    To determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo. In this replication and extension study of a previous clinical trial, we tested the impact of low-dose naltrexone on daily self-reported pain. Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue.Thirty-one women with fibromyalgia participated in the randomized, double-blind, placebo-controlled, counterbalanced, crossover study. During the active drug phase, participants received 4.5 mg of oral naltrexone daily. An intensive longitudinal design was used to measure daily levels of pain.When contrasting the condition end points, we observed a significantly greater reduction of baseline pain in those taking low-dose naltrexone than in those taking placebo (28.8% reduction versus 18.0% reduction; P = 0.016). Low-dose naltrexone was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but not improved fatigue or sleep. Thirty-two percent of participants met the criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during low-dose naltrexone therapy, as contrasted with an 11% response rate during placebo therapy (P = 0.05). Low-dose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported.The preliminary evidence continues to show that low-dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well-tolerated. Parallel-group randomized controlled trials are needed to fully determine the efficacy of the medication.

    View details for DOI 10.1002/art.37734

    View details for Web of Science ID 000314169400030

  • Pain in chronic medical illness. Pain research and treatment Brown, J., Younger, J., Madan, A., Borckardt, J. 2013; 2013: 615967-?

    View details for DOI 10.1155/2013/615967

    View details for PubMedID 23401766

  • Development of the Stanford Expectations of Treatment Scale (SETS): A tool for measuring patient outcome expectancy in clinical trials CLINICAL TRIALS Younger, J., Gandhi, V., Hubbard, E., Mackey, S. 2012; 9 (6): 767-776


    A patient's response to treatment may be influenced by the expectations that the patient has before initiating treatment. In the context of clinical trials, the influence of participant expectancy may blur the distinction between real and sham treatments, reducing statistical power to detect specific treatment effects. There is therefore a need for a tool that prospectively predicts expectancy effects on treatment outcomes across a wide range of treatment modalities.To help assess expectancy effects, we created the Stanford Expectations of Treatment Scale (SETS): an instrument for measuring positive and negative treatment expectancies. Internal reliability of the instrument was tested in Study 1. Criterion validity of the instrument (convergent, discriminant, and predictive) was assessed in Studies 2 and 3.The instrument was developed using 200 participants in Study 1. Reliability and validity assessments were made with an additional 423 participants in Studies 2 and 3.The final six-item SETS contains two subscales: positive expectancy (? = 0.81-0.88) and negative expectancy (? = 0.81-0.86). The subscales predict a significant amount of outcome variance (between 12% and 18%) in patients receiving surgical and pain interventions. The SETS is simple to administer, score, and interpret.The SETS may be used in clinical trials to improve statistical sensitivity for detecting treatment differences or in clinical settings to identify patients with poor treatment expectancies.

    View details for DOI 10.1177/1740774512465064

    View details for Web of Science ID 000312452600015

    View details for PubMedID 23169874

  • A Pilot Cohort Study of the Determinants of Longitudinal Opioid Use After Surgery ANESTHESIA AND ANALGESIA Carroll, I., Barelka, P., Wang, C. K., Wang, B. M., Gillespie, M. J., McCue, R., Younger, J. W., Trafton, J., Humphreys, K., Goodman, S. B., Dirbas, F., Whyte, R. I., Donington, J. S., Cannon, W. B., Mackey, S. C. 2012; 115 (3): 694-702


    Determinants of the duration of opioid use after surgery have not been reported. We hypothesized that both preoperative psychological distress and substance abuse would predict more prolonged opioid use after surgery.Between January 2007 and April 2009, a prospective, longitudinal inception cohort study enrolled 109 of 134 consecutively approached patients undergoing mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement. We measured preoperative psychological distress and substance use, and then measured the daily use of opioids until patients reported the cessation of both opioid consumption and pain. The primary end point was time to opioid cessation. All analyses were controlled for the type of surgery done.Overall, 6% of patients continued on new opioids 150 days after surgery. Preoperative prescribed opioid use, depressive symptoms, and increased self-perceived risk of addiction were each independently associated with more prolonged opioid use. Preoperative prescribed opioid use was associated with a 73% (95% confidence interval [CI] 0.51%-87%) reduction in the rate of opioid cessation after surgery (P = 0.0009). Additionally, each 1-point increase (on a 4-point scale) of self-perceived risk of addiction was associated with a 53% (95% CI 23%-71%) reduction in the rate of opioid cessation (P = 0.003). Independent of preoperative opioid use and self-perceived risk of addiction, each 10-point increase on a preoperative Beck Depression Inventory II was associated with a 42% (95% CI 18%-58%) reduction in the rate of opioid cessation (P = 0.002). The variance in the duration of postoperative opioid use was better predicted by preoperative prescribed opioid use, self-perceived risk of addiction, and depressive symptoms than postoperative pain duration or severity.Preoperative factors, including legitimate prescribed opioid use, self-perceived risk of addiction, and depressive symptoms each independently predicted more prolonged opioid use after surgery. Each of these factors was a better predictor of prolonged opioid use than postoperative pain duration or severity.

    View details for DOI 10.1213/ANE.0b013e31825c049f

    View details for Web of Science ID 000307942900028

    View details for PubMedID 22729963

  • Visualization of Painful Experiences Believed to Trigger the Activation of Affective and Emotional Brain Regions in Subjects with Low Back Pain PLOS ONE Shimo, K., Ueno, T., Younger, J., Nishihara, M., Inoue, S., Ikemoto, T., Taniguchi, S., Ushida, T. 2011; 6 (11)


    In the management of clinical low back pain (LBP), actual damage to lower back areas such as muscles, intervertebral discs etc. are normally targeted for therapy. However, LBP may involve not only sensory pain, but also underlying affective pain which may also play an important role overall in painful events. Therefore we hypothesized that visualization of a painful event may trigger painful memories, thus provoking the affective dimension of pain. The present study investigated neural correlates of affect processing in subjects with LBP (n = 11) and subjects without LBP (n = 11) through the use of virtual LBP stimuli. Whole brain functional magnetic resonance imaging (MRI) was performed for all subjects while they were shown a picture of a man carrying luggage in a half-crouching position. All subjects with LBP reported experiencing discomfort and 7 LBP subjects reported experiencing pain. In contrast to subjects without LBP, subjects with LBP displayed activation of the cortical area related to pain and emotions: the insula, supplementary motor area, premotor area, thalamus, pulvinar, posterior cingulate cortex, hippocampus, fusiform, gyrus, and cerebellum. These results suggest that the virtual LBP stimuli caused memory retrieval of unpleasant experiences and therefore may be associated with prolonged chronic LBP conditions.

    View details for DOI 10.1371/journal.pone.0026681

    View details for Web of Science ID 000297154900031

    View details for PubMedID 22073183

  • Towards a Physiology-Based Measure of Pain: Patterns of Human Brain Activity Distinguish Painful from Non-Painful Thermal Stimulation PLOS ONE Brown, J. E., Chatterjee, N., Younger, J., Mackey, S. 2011; 6 (9)


    Pain often exists in the absence of observable injury; therefore, the gold standard for pain assessment has long been self-report. Because the inability to verbally communicate can prevent effective pain management, research efforts have focused on the development of a tool that accurately assesses pain without depending on self-report. Those previous efforts have not proven successful at substituting self-report with a clinically valid, physiology-based measure of pain. Recent neuroimaging data suggest that functional magnetic resonance imaging (fMRI) and support vector machine (SVM) learning can be jointly used to accurately assess cognitive states. Therefore, we hypothesized that an SVM trained on fMRI data can assess pain in the absence of self-report. In fMRI experiments, 24 individuals were presented painful and nonpainful thermal stimuli. Using eight individuals, we trained a linear SVM to distinguish these stimuli using whole-brain patterns of activity. We assessed the performance of this trained SVM model by testing it on 16 individuals whose data were not used for training. The whole-brain SVM was 81% accurate at distinguishing painful from non-painful stimuli (p<0.0000001). Using distance from the SVM hyperplane as a confidence measure, accuracy was further increased to 84%, albeit at the expense of excluding 15% of the stimuli that were the most difficult to classify. Overall performance of the SVM was primarily affected by activity in pain-processing regions of the brain including the primary somatosensory cortex, secondary somatosensory cortex, insular cortex, primary motor cortex, and cingulate cortex. Region of interest (ROI) analyses revealed that whole-brain patterns of activity led to more accurate classification than localized activity from individual brain regions. Our findings demonstrate that fMRI with SVM learning can assess pain without requiring any communication from the person being tested. We outline tasks that should be completed to advance this approach toward use in clinical settings.

    View details for DOI 10.1371/journal.pone.0024124

    View details for Web of Science ID 000295321800020

    View details for PubMedID 21931652

  • Prescription opioid analgesics rapidly change the human brain PAIN Younger, J. W., Chu, L. F., D'Arcy, N. T., Trott, K. E., Jastrzab, L. E., Mackey, S. C. 2011; 152 (8): 1803-1810


    Chronic opioid exposure is known to produce neuroplastic changes in animals; however, it is not known if opioids used over short periods of time and at analgesic dosages can similarly change brain structure in humans. In this longitudinal, magnetic resonance imaging study, 10 individuals with chronic low back pain were administered oral morphine daily for 1 month. High-resolution anatomical images of the brain were acquired immediately before and after the morphine administration period. Regional changes in gray matter volume were assessed on the whole brain using tensor-based morphometry, and those significant regional changes were then independently tested for correlation with morphine dosage. Thirteen regions evidenced significant volumetric change, and degree of change in several of the regions was correlated with morphine dosage. Dosage-correlated volumetric decrease was observed primarily in the right amygdala. Dosage-correlated volumetric increase was seen in the right hypothalamus, left inferior frontal gyrus, right ventral posterior cingulate, and right caudal pons. Follow-up scans that were conducted an average of 4.7 months after cessation of opioids demonstrated many of the morphine-induced changes to be persistent. In a separate study, 9 individuals consuming blinded placebo capsules for 6 weeks evidenced no significant morphologic changes over time. The results add to a growing body of literature showing that opioid exposure causes structural and functional changes in reward- and affect-processing circuitry. Morphologic changes occur rapidly in humans during new exposure to prescription opioid analgesics. Further research is needed to determine the clinical impact of those opioid-induced gray matter changes.

    View details for DOI 10.1016/j.pain.2011.03.028

    View details for Web of Science ID 000292862400020

    View details for PubMedID 21531077

  • Viewing Pictures of a Romantic Partner Reduces Experimental Pain: Involvement of Neural Reward Systems PLOS ONE Younger, J., Aron, A., Parke, S., Chatterjee, N., Mackey, S. 2010; 5 (10)


    The early stages of a new romantic relationship are characterized by intense feelings of euphoria, well-being, and preoccupation with the romantic partner. Neuroimaging research has linked those feelings to activation of reward systems in the human brain. The results of those studies may be relevant to pain management in humans, as basic animal research has shown that pharmacologic activation of reward systems can substantially reduce pain. Indeed, viewing pictures of a romantic partner was recently demonstrated to reduce experimental thermal pain. We hypothesized that pain relief evoked by viewing pictures of a romantic partner would be associated with neural activations in reward-processing centers. In this functional magnetic resonance imaging (fMRI) study, we examined fifteen individuals in the first nine months of a new, romantic relationship. Participants completed three tasks under periods of moderate and high thermal pain: 1) viewing pictures of their romantic partner, 2) viewing pictures of an equally attractive and familiar acquaintance, and 3) a word-association distraction task previously demonstrated to reduce pain. The partner and distraction tasks both significantly reduced self-reported pain, although only the partner task was associated with activation of reward systems. Greater analgesia while viewing pictures of a romantic partner was associated with increased activity in several reward-processing regions, including the caudate head, nucleus accumbens, lateral orbitofrontal cortex, amygdala, and dorsolateral prefrontal cortex--regions not associated with distraction-induced analgesia. The results suggest that the activation of neural reward systems via non-pharmacologic means can reduce the experience of pain.

    View details for DOI 10.1371/journal.pone.0013309

    View details for Web of Science ID 000282869800015

    View details for PubMedID 20967200

  • Chronic myofascial temporomandibular pain is associated with neural abnormalities in the trigeminal and limbic systems PAIN Younger, J. W., Shen, Y. F., Goddard, G., Mackey, S. C. 2010; 149 (2): 222-228


    Myofascial pain of the temporomandibular region (M-TMD) is a common, but poorly understood chronic disorder. It is unknown whether the condition is a peripheral problem, or a disorder of the central nervous system (CNS). To investigate possible CNS substrates of M-TMD, we compared the brain morphology of 15 women with M-TMD to that of 15 age- and gender-matched healthy controls. High-resolution structural brain and brainstem scans were carried out using magnetic resonance imaging (MRI), and data were analyzed using a voxel-based morphometry approach. The M-TMD group evidenced decreased or increased gray matter volume compared to controls in several areas of the trigeminothalamocortical pathway, including brainstem trigeminal sensory nuclei, the thalamus, and the primary somatosensory cortex. In addition, M-TMD individuals showed increased gray matter volume compared to controls in limbic regions such as the posterior putamen, globus pallidus, and anterior insula. Within the M-TMD group, jaw pain, pain tolerance, and pain duration were differentially associated with brain and brainstem gray matter volume. Self-reported pain severity was associated with increased gray matter in the rostral anterior cingulate cortex and posterior cingulate. Sensitivity to pressure algometry was associated with decreased gray matter in the pons, corresponding to the trigeminal sensory nuclei. Longer pain duration was associated with greater gray matter in the posterior cingulate, hippocampus, midbrain, and cerebellum. The pattern of gray matter abnormality found in M-TMD individuals suggests the involvement of trigeminal and limbic system dysregulation, as well as potential somatotopic reorganization in the putamen, thalamus, and somatosensory cortex.

    View details for DOI 10.1016/j.pain.2010.01.006

    View details for Web of Science ID 000276980900012

    View details for PubMedID 20236763

  • Pain Quality Predicts Lidocaine Analgesia among Patients with Suspected Neuropathic Pain PAIN MEDICINE Carroll, I. R., Younger, J. W., Mackey, S. C. 2010; 11 (4): 617-621


    Oral sodium channel blockers have shown mixed results in randomized controlled trials despite the known importance of sodium channels in generating pain. We hypothesized that differing baseline pain qualities (e.g. "stabbing" vs "dull") might define specific subgroups responsive to intravenous (IV) lidocaine-a potent sodium channel blocker.A prospective cohort study of 71 patient with chronic pain suspected of being neuropathic were recruited between January 2003 and July 2007 and underwent lidocaine infusions at Stanford University Hospital in a single-blind nonrandomized fashion. Baseline sensory pain qualities were measured with the Short-Form McGill Pain Questionnaire (SF-MPQ). Pain intensity was measured with a visual analog scale (VAS).Factor analysis demonstrated two underlying pain quality factors among SF-MPQ sensory items: a heavy pain and a stabbing pain. Baseline heavy pain quality, but not stabbing quality predicted subsequent relief of pain intensity in response to lidocaine. In contrast, these factors did not predict divergent analgesic responses to placebo infusions. In response to each 1 mcg/mL increase in lidocaine plasma level, patients with high heavy pain quality drop their VAS 0.24 (95% CI 0.05-0.43) more points than those with low heavy pain quality (P < 0.013)."Heavy" pain quality may indentify patients with enhanced lidocaine responsiveness. Pain quality may identify subgroups among patients with suspected neuropathic pain responsive to IV lidocaine. Further investigation is warranted to validate and extend these findings.

    View details for Web of Science ID 000276223500020

    View details for PubMedID 20210867

  • Randomized Clinical Trial of Acupuncture for Myofascial Pain of the Jaw Muscles JOURNAL OF OROFACIAL PAIN Shen, Y. F., Younger, J., Goddard, G., Mackey, S. 2009; 23 (4): 353-359


    To evaluate the effectiveness of acupuncture in treating symptoms associated with myofascial pain of the jaw muscles.Twenty-eight subjects over the age of 18 and diagnosed with chronic myofascial pain of the jaw muscles were randomized to receive real (n = 16) or sham (n = 12) acupuncture. Prior to treatment, each subject clenched his or her teeth for 2 minutes. Acupuncture or sham acupuncture was then administered at the Hegu large intestine 4 (LI4) acupoint for 15 minutes. Real acupuncture was given by penetrating the needle through a sticky foam pad at the acupoint. Sham acupuncture was conducted by pricking the skin, without penetration, with a shortened, blunted acupuncture needle through a foam pad placed away from the acupoint. General head and neck pain ratings were obtained before and after treatment on a numerical rating scale. A mechanical pain stimulus on the masseter muscle was given before and after treatment and rated on a visual analog scale to measure pain tolerance level. Paired t tests were performed to detect significant changes in pain levels.Subjects receiving real acupuncture experienced a significant reduction in jaw pain (P = .04), jaw/face tightness (P = .04), and neck pain (P = .04), and a significant increase in pain tolerance of the masseter muscle (P = .001). Subjects were not able to determine whether they received real or sham acupuncture (P = .69). No significant pain reductions were observed in the sham acupuncture group.A single acupuncture session using one acupoint at Hegu large intestine 4 significantly reduced most myofascial pain endpoints when compared to sham acupuncture.

    View details for Web of Science ID 000271823900014

    View details for PubMedID 19888488

  • Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study PAIN MEDICINE Younger, J., Mackey, S. 2009; 10 (4): 663-672


    Fibromyalgia is a chronic pain disorder that is characterized by diffuse musculoskeletal pain and sensitivity to mechanical stimulation. In this pilot clinical trial, we tested the effectiveness of low-dose naltrexone in treating the symptoms of fibromyalgia.Participants completed a single-blind, crossover trial with the following time line: baseline (2 weeks), placebo (2 weeks), drug (8 weeks), and washout (2 weeks).Ten women meeting criteria for fibromyalgia and not taking an opioid medication.Naltrexone, in addition to antagonizing opioid receptors on neurons, also inhibits microglia activity in the central nervous system. At low doses (4.5 mg), naltrexone may inhibit the activity of microglia and reverse central and peripheral inflammation.Participants completed reports of symptom severity everyday, using a handheld computer. In addition, participants visited the lab every 2 weeks for tests of mechanical, heat, and cold pain sensitivity.Low-dose naltrexone reduced fibromyalgia symptoms in the entire cohort, with a greater than 30% reduction of symptoms over placebo. In addition, laboratory visits showed that mechanical and heat pain thresholds were improved by the drug. Side effects (including insomnia and vivid dreams) were rare, and described as minor and transient. Baseline erythrocyte sedimentation rate predicted over 80% of the variance in drug response. Individuals with higher sedimentation rates (indicating general inflammatory processes) had the greatest reduction of symptoms in response to low-dose naltrexone.We conclude that low-dose naltrexone may be an effective, highly tolerable, and inexpensive treatment for fibromyalgia.

    View details for DOI 10.1111/j.1526-4637.2009.00613.x

    View details for Web of Science ID 000266678600010

    View details for PubMedID 19453963

  • Effects of Naltrexone on Pain Sensitivity and Mood in Fibromyalgia: No Evidence for Endogenous Opioid Pathophysiology PLOS ONE Younger, J. W., Zautra, A. J., Cummins, E. T. 2009; 4 (4)


    The pathophysiological mechanisms underlying fibromyalgia are still unknown, although some evidence points to endogenous opioid dysfunction. We examined how endogenous opioid antagonism affects pain and mood for women with and without fibromyalgia. Ten women with fibromyalgia and ten age- and gender-matched, healthy controls each attended two laboratory sessions. Each participant received naltrexone (50mg) at one session, and placebo at the other session, in a randomized and double-blind fashion. Participants were tested for changes in sensitivity to heat, cold, and mechanical pain. Additionally, we collected measures of mood and opioid withdrawal symptoms during the laboratory sessions and at home the night following each session. At baseline, the fibromyalgia group exhibited more somatic complaints, greater sensory sensitivity, more opioid withdrawal somatic symptoms, and lower mechanical and cold pain-tolerance than did the healthy control group. Neither group experienced changes in pain sensitivity due to naltrexone administration. Naltrexone did not differentially affect self-reported withdrawal symptoms, or mood, in the fibromyalgia and control groups. Consistent with prior research, there was no evidence found for abnormal endogenous opioid activity in women with fibromyalgia.

    View details for DOI 10.1371/journal.pone.0005180

    View details for Web of Science ID 000265509900010

    View details for PubMedID 19365548

  • Pain outcomes: A brief review of instruments and techniques CURRENT PAIN AND HEADACHE REPORTS Younger, J., McCue, R., Mackey, S. 2009; 13 (1): 39-43


    Pain is a difficult outcome to measure due to its multifaceted and subjective nature. The need for selecting proper outcome measures is high because of the increasing demand for scientifically valid demonstrations of treatment efficacy. This article discusses some basic topics in the measurement of pain outcomes and addresses issues such as statistical versus clinical significance, daily home data collection, appropriate length of outcome measurement packets, and the possibility of objective pain measurements. This article also reviews some of the more commonly used tools for measuring pain and pain-related disability. By selecting the proper tools and employing them correctly, we can obtain highly reliable and valid measures of pain outcomes in research and clinical care.

    View details for DOI 10.1007/s11916-009-0009-x

    View details for Web of Science ID 000263064900009

    View details for PubMedID 19126370

  • Reduced Cold Pain Tolerance in Chronic Pain Patients Following Opioid Detoxification PAIN MEDICINE Younger, J., Barelka, P., Carroll, I., Kaplan, K., Chu, L., Prasad, R., Gaeta, R., Mackey, S. 2008; 9 (8): 1158-1163


    One potential consequence of chronic opioid analgesic administration is a paradoxical increase of pain sensitivity over time. Little scientific attention has been given to how cessation of opioid medication affects the hyperalgesic state. In this study, we examined the effects of opioid tapering on pain sensitivity in chronic pain patients.Twelve chronic pain patients on long-term opioid analgesic treatment were observed in a 7- to 14-day inpatient pain rehabilitation program, with cold pain tolerance assessed at admission and discharge. The majority of participants were completely withdrawn from their opioids during their stay.We hypothesized that those patients with the greatest reduction in daily opioid use would show the greatest increases in pain tolerance, as assessed by a cold pressor task.A linear regression revealed that the amount of opioid medication withdrawn was a significant predictor of pain tolerance changes, but not in the direction hypothesized. Greater opioid reduction was associated with decreased pain tolerance. This reduction of pain tolerance was not associated with opioid withdrawal symptoms or changes in general pain.These findings suggest that the withdrawal of opioids in a chronic pain sample leads to an acute increase in pain sensitivity.

    View details for DOI 10.1111/j.1526-4637.2008.00475.x

    View details for Web of Science ID 000261106100026

    View details for PubMedID 18564998

  • Chronic stress and regulation of cellular markers of inflammation in rheumatoid arthritis: Implications for fatigue BRAIN BEHAVIOR AND IMMUNITY Davis, M. C., Zautra, A. J., Younger, J., Motivala, S. J., Attrep, J., Irwin, M. R. 2008; 22 (1): 24-32


    This study examined whether chronic interpersonal stress is associated with cellular markers of inflammation and regulation of these responses by in vitro doses of glucocorticoids in rheumatoid arthritis (RA) patients. The association between these markers of inflammation and fatigue was also tested.Fifty-eight RA patients completed up to 30 daily ratings of the stressfulness of their interpersonal relations. Interleukin-6 (IL-6) production was analyzed in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cell cultures with and without varying concentrations of the glucocorticoid hydrocortisone. In addition, plasma levels of IL-6 and C-reactive protein (CRP) were analyzed, and subjective ratings of fatigue and pain were obtained on the day of blood sampling.Multilevel modeling showed that higher chronic interpersonal stress was associated with greater stimulated IL-6 production (p<0.05) as well as greater resistance to hydrocortisone inhibition of IL-6 production (p<0.05). These relations were not accounted for by demographic factors, body mass index, or steroid medication use. Stimulated production of IL-6, in turn, was associated with greater levels of self-reported fatigue, controlling for pain (p<0.05). Neither chronic stress ratings nor fatigue symptoms were related to plasma levels of IL-6 or CRP (ps>.05).Among RA patients, chronic interpersonal stress is associated with greater stimulated cellular production of IL-6 along with impairments in the capacity of glucocorticoids to inhibit this cellular inflammatory response. Moreover, these findings add to a growing body of data that implicate heightened proinflammatory cytokine activity in those at risk for fatigue symptoms.

    View details for DOI 10.1016/j.bbi.2007.06.013

    View details for Web of Science ID 000252375800005

    View details for PubMedID 17706915

  • Personal mastery predicts pain, stress, fatigue, and blood pressure in adults with rheumatoid arthritis PSYCHOLOGY & HEALTH Younger, J., Finan, P., Zautra, A., Davis, M., Reich, J. 2008; 23 (5): 515-535
  • Hypnotizability and somatic complaints: A gender-specific phenomenon INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL HYPNOSIS Younger, J. W., Rossetti, G. C., Borckardt, J. J., Smith, A. R., Tasso, A. F., Nash, M. R. 2007; 55 (1): 1-13


    The relationship between hypnotizability and somatic illness was measured in 45 college students. Several weeks after completing the Waterloo-Stanford Group C Scale (WSGC), participants filled out a somatic-complaint checklist and measures of psychopathology. Results indicated a positive correlation between hypnotizability and somatic illness, and the relationship was stronger for female participants. In contrast to the quadratic model proposed by Wickramasekera, the current data demonstrated a linear relationship between hypnotizability and somatic complaint. Further analyses showed that somatic complaints were associated with hallucination and imagery items, corresponding to the perceptual-cognitive factor identified in Woody, Barnier, and McConkey's (2005) factor analysis of the Stanford Hypnotic Susceptibility Scale, Form C. The results call into question some claims that high hypnotizability is an adaptive and healthy trait.

    View details for DOI 10.1080/00207140600995745

    View details for Web of Science ID 000242557700001

    View details for PubMedID 17135060

  • The role of adult attachment style in forgiveness following an interpersonal offense JOURNAL OF COUNSELING AND DEVELOPMENT Lawler-Row, K. A., Younger, J. W., Piferi, R. L., Jones, W. H. 2006; 84 (4): 493-502
  • Effects of naltrexone on repressive coping and disclosure of emotional material: A test of the opioid-peptide hypothesis of repression and hypertension PSYCHOSOMATIC MEDICINE Younger, J. W., Lawler-Row, K. A., Moe, K. A., Kratz, A. L., Keenum, A. J. 2006; 68 (5): 734-741


    The present study was designed to assess the role of endogenous opioids in the relationship of hypertension to repressive coping.Ten hypertensive and 8 normotensive males were given either the opioid antagonist naltrexone or placebo in a randomized, double-blind fashion over the course of four laboratory sessions. Measures of repression and disclosure were completed and blood pressure was assessed during a laboratory stressor protocol.Opioid antagonism reduced repression and increased disclosure only in the hypertensive group. Also, opioid antagonism increased stress-related systolic blood pressure only in the hypertensive group.The results support the hypothesis that endogenous opioid dysregulation underlies both hypertension and repressive phenomena.

    View details for DOI 10.1097/01.psy.0000234029.38245.o9

    View details for Web of Science ID 000241205700013

    View details for PubMedID 17012527

  • Anatomy of a hypnotic response: Self-report estimates, actual behavior, and physiological response to the hypnotic suggestion for arm rigidity INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL HYPNOSIS Winkel, J. D., Younger, J. W., Tomcik, N., Borckardt, J. J., Nash, M. R. 2006; 54 (2): 186-205


    The present study closely examines subject response to the arm-rigidity item of the HGSHS:A. Subject behavior, subject self-report, and surface EMG of the biceps and triceps muscles were monitored. Two distinct ways of passing the item were observed and verified by EMG recordings: some subjects (tremblers) exerted muscular effort to bend the arm and kept it rigidly straight. Others (nontremblers) passively kept the arm straight without exerting muscular effort to bend, even though they reported exerting effort to bend their arm. These two behaviorally and physiologically different methods of passing the item support the idea of individual differences in hypnotic responding and suggest that subjects may be using different mental processes to pass the item.

    View details for DOI 10.1080/00207140500528430

    View details for Web of Science ID 000236610100005

    View details for PubMedID 16581690

  • The role of adult attachement style in forgiveness following an interpersonal offense. Journal of Counseling and Development Lawler K, Younger J, Piferi R, Jones W 2006; 84: 493-502
  • The Harvard group scale of hypnotic susceptibility: Accuracy of self-report and the memory for items INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL HYPNOSIS Younger, J., Kemmerer, D. D., Winkel, J. D., Nash, M. R. 2005; 53 (3): 306-320


    Whereas early studies have found moderately high agreement between self- and observer-rated scores on the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A), these studies shared a common confound in that participants were aware of being directly observed. In the present study, confederates made surreptitious observations of group participants' hypnotic responding. Following the hypnotic procedure, participants indicated whether or not they remembered each item and provided self-reports of their hypnotic response. The study assesses the accuracy of participant self-report for hypnosis items when individuals are unaware of being observed. Thirty-two percent of participants failed to recognize at least one item from the hypnosis session, suggesting that the inability to remember items is a common phenomenon. When participants reported not remembering an item, the accuracy of their self-reported response was no better than chance.

    View details for DOI 10.1080/00207140590961411

    View details for Web of Science ID 000230417800008

    View details for PubMedID 16076667

  • Spirituality predicts health and cardiovascular responses to stress in young adult women JOURNAL OF RELIGION & HEALTH Edmondson, K. A., Lawler, K. A., Jobe, R. L., Younger, J. W., Piferi, R. L., Jones, W. H. 2005; 44 (2): 161-171
  • The unique effects of forgiveness on health: An exploration of pathways JOURNAL OF BEHAVIORAL MEDICINE Lawler, K. A., Younger, J. W., Piferi, R. L., Jobe, R. L., Edmondson, K. A., Jones, W. H. 2005; 28 (2): 157-167


    The relationship of forgiveness, both state and trait, to health was assessed. Eighty-one community adults completed a packet of questionnaires and participated in a laboratory interview about a time of hurt or betrayal. Heart rate and blood pressure were recorded during a 10 min baseline, the interview and during a recovery period; interviews were structured around a framework of questions and videotaped. Four measures of forgiveness were all statistically associated with five measures of health (physical symptoms, medications used, sleep quality, fatigue, and somatic complaints). Trait forgiveness was associated with decreased reactivity (rate-pressure product) to the interview, but sympathetic reactivity did not account for the trait forgiveness-health association. Four mechanisms or pathways by which forgiveness could lead to fewer physical symptoms were examined: spirituality, social skills, reduction in negative affect, and reduction in stress. All factors either partially or fully mediated the effect of forgiveness on health; however, the strongest mediator for both state and trait forgiveness was reduction in negative affect. For state forgiveness, the second strongest mediator was reduction in stress; for trait forgiveness, both conflict management and reduction in stress were strong contributors.

    View details for DOI 10.1007/s10865-005-3665-2

    View details for Web of Science ID 000228856200005

    View details for PubMedID 15957571

  • Dimensions of forgiveness: The views of laypersons JOURNAL OF SOCIAL AND PERSONAL RELATIONSHIPS Younger, J. W., Piferi, R. L., Jobe, R. L., Lawler, K. A. 2004; 21 (6): 837-855
  • The computer-assisted cognitive/imagery system for use in the management of pain. Pain research & management Borckardt, J. J., Younger, J., Winkel, J., Nash, M. R., Shaw, D. 2004; 9 (3): 157-162


    There is growing interest in computer-delivered psychological interventions for a number of clinical conditions, including pain.This study tests the effectiveness of a new computer-delivered pain-management program using a laboratory pain paradigm.One hundred twenty undergraduate students were randomly assigned to either the computerized pain-management group or the distraction control group. Subjects underwent a cold-pressor task and were asked to continuously rate their subjective pain experience.Women receiving the computerized pain management intervention were able to tolerate the cold-pressor task longer than those in the control group. No effect was found for men. Subjective pain ratings were consistently lower during the cold-pressor task for subjects in the computerized pain-management group regardless of sex. Subjects receiving the computerized intervention reported feeling more comfortable and relaxed than control subjects during the cold-pressor task.Findings indicate that further investigations of the program used in this study are warranted to determine its potential clinical utility and that of similar computerized interventions for pain.

    View details for PubMedID 15340586

  • Dimensions of forgiveness: the views of laypersons Journal of Social and Personal Relationships Younger J, Piferi R, Jobe R, Lawer K 2004; 21: 837-855
  • A change of heart: Cardiovascular correlates of forgiveness in response to interpersonal conflict JOURNAL OF BEHAVIORAL MEDICINE Lawler, K. A., Younger, J. W., Piferi, R. L., Billington, E., Jobe, R., Edmondson, K., Jones, W. H. 2003; 26 (5): 373-393


    This study sought to examine the psychophysiological correlates of forgiveness in response to interpersonal conflict. One hundred eight college students (44 males and 64 females) participated in two interviews about times of interpersonal betrayal, one about a parent and one about a friend/partner. Measures of forgiving personality and state forgiveness were collected, as well as stress, hostility, empathy, and self-reported illness symptoms. During baseline, interviews and recovery periods, repeated measures were taken of blood pressure, heart rate, frontalis EMG, and skin conductance. Trait forgiveness was associated with lower levels of blood pressure. State forgiveness was associated with lower blood pressure levels, heart rate, and rate pressure product. Acute, stress-induced reactivity was also linked to forgiveness: state forgiveness was associated with diastolic and mean arterial pressure and rate pressure product reactivity during the parent interview. Increased blood pressure recovery after stress was also linked to trait forgiveness. Forgiveness may produce beneficial effects directly by reducing allostatic load associated with betrayal and conflict, and indirectly through reductions in perceived stress.

    View details for Web of Science ID 000185302300001

    View details for PubMedID 14593849

  • Theobiology: An analysis of spirituality, cardiovascular responses, stress, mood, and physical health JOURNAL OF RELIGION & HEALTH Lawler, K. A., Younger, J. W. 2002; 41 (4): 347-362
  • An alternative approach for achieving cardiovascular baseline: viewing an aquatic video INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY Piferi, R. L., Kline, K. A., Younger, J., Lawler, K. A. 2000; 37 (2): 207-217


    Due to the importance of baseline and recovery levels in the computation of reactivity, two studies were conducted to determine an alternative method to traditional rest for achieving baseline and recovery levels of cardiovascular measurements. Watching a relaxing, aquatic video was compared with a traditional resting baseline to determine the better method for achieving low baseline levels. In addition, watching the video was compared with traditional rest during 5-min post-task recovery periods. Systolic (SBP) and diastolic blood pressure (DBP) decreased more during the baseline period when subjects viewed the video than when subjects rested quietly. Similarly, subjects displayed greater recovery following the mental tasks when they watched a video than when they merely sat quietly. It is recommended that researchers standardize baseline procedures by showing a relaxing video before administering tasks for the assessment of cardiovascular reactivity.

    View details for Web of Science ID 000087758100009

    View details for PubMedID 10832007

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