University of Florida | Journal of Undergraduate Research | Volume 1 9 Issue 2 | Spring 201 8 1 Examining the Impact of a Resilience Based Hope Intervention on Pain Evoked Cortisol Response Nadia I. Hossain, Michael E. Robinson Roger B. Fillingim & Emily J. Bartley College of Liberal Arts and Sciences, Department of Community Dentistry and Behavioral Science, Department of Clinical and Health Psychology, Pain Research & Intervention Center of Excellence (PRICE), Center for Pain Research and Behavioral Health Univers ity of Florida T emporomandibular disorder is an orofacial pain condition often resulting in functional impairment and pain related disability Given the relationship between stress and pain in T emporomandibular disorder it has been suggested that dysregul ation of the hypo thalamic pituitary adrenal axis (e.g., cortisol responsivity) could contribute to the onset and maintenance of the condition. Research has shown that therapies to control pain and stress can improve quality of life in patients with persist ent pain, with recent evidence supporting resilience as a pot ential target of intervention. However, no studies have systematically examined whether a resilience intervention has efficacy in modulating neuroendocrine functioning in T emporomandibular disord er Therefore, the primary objective of this pilot study was to investigate the effects of a resilience based hope intervention on pain evoked cortisol levels in individuals with T emporomandibular disorder Twenty nine participants were randomized to a 3 s ession intervention intended to increase hope or a control intervention targeting pain and stress education. Prior to and after the intervention, participants attended two expe rimental sessions whereby salivary cortisol was obtained after the induction of a painful, cold water procedure. While there were no intervention group differences in pain evoked cortisol response, greater situational and dispositional hope were associated with lower levels of cortisol. Overall, findings suggest that positive emotiona l resources may attenuate heightened neuroendocrine activity; however, further research is needed to determine the physiological benefits of resilience oriented therapies. INTRODUCTION emporomandibular disorders (TMD) are a group of orofacial pain conditions primarily affecting the temporomandibular joint and muscles of mastication. TMD often results in reduced work related productivity and decreased quality of life (Sherman et al., 2005) and patients are at increased risk for other health related conditions such as irritable bowel syndrome, interstitial cystitis, and mood disorders (Furquim, Flamengui, & Conti, 2015) Causes of TMD are complex and multifactorial but can include oral parafunctional behaviors (i.e., b ruxism, teeth clenching), misalignment of the teeth/jaw, and/or emotional factors such as depression or anxiety (Sharma, Gupta, Pal, & Jurel, 2011; Slade et al., 2016) Alterations in basal and stress induced hypothalamic pituitary adrena l axis (HPA) activity have been implicated in TMD pathogenesis, with evidence supporting dysregulated stress and cortisol responses in individuals with TMD (Lambert et al., 2013; Ulrich Lai et al., 2006) Given the multi systemi c effects of the HPA axis, it has been suggested that disruptions in HPA activity may influence central and neural pathways responsible for the transmission and modulation of pain (Ulrich Lai et al., 2006) Supporting the relationship betwe en stress and pain, Jones and colleagues found that TMD patients secreted higher levels of cortisol in response to experimental stress in comparison to healthy pain free individuals (Jon es, Rollman, & Brooke, 1997) signifying an exaggerated physiological response to stress in this population. Lambert et al. also reported that TMD participants perceive higher amounts of stress than healthy, pain free individuals (Lambert et al., 2013) Because TMD symptoms often increase during stress, mechanisms associated with the dysr egulation of cortisol reactivity in this population could contribute to the development and/or maintenance of TMD symptoms and pain. Treatments for TMD have historically focused on invasive medical and dental procedures, intraoral appliances, and medicati ons; however, these approaches show modest efficacy and provide insufficient long term improvement in pain (Sherman & Turk, 2001) As a result, psychosocially based interventions to ease pain related suffering have been supported, with recent efforts directed towards examining resilience in the context of pain coping. Resilience is the process of successful adaptation after trauma, adversity, or severe stress, and evidence supports the positive role that resilience has on mental well being, pain acceptance, and physical health (Sturgeon & Zautra, 2010) While scant, there is a growing body of literature investigating the effects of therapeutic approaches that foster resilience and positive mental health. Resilience oriented treatments work toward enhancing personal T
N ADIA H OSSAIN MICHAEL ROBINSON ROGER FILLINGIM & E MILY B ARTLEY University of Florida | Journal of Undergraduate Research | Volume 1 9 Issue 2 | Spring 201 8 2 s trengths and coping resources to increase goal directed behavior and hopeful thinking in the face of adversity. For instance, Hanssen and colleagues examined the influence of optimism on experimental pain in healthy adults via the Best Possible Self (BPS) exercise. The authors found that participants in this optimism intervention reported lower pain intensity ratings compared to the control group (Hanssen, Peters, Vlaeyen, Meevissen, & Vancleef, 2013) Using a similar paradigm, Boselie and colleagues examined whether an optimism manipulation eliminated pain induced interfere nce with cognitive performance. While experimentally induced pain (i.e., cold pressor) reduced performance on the memory task, generating an optimistic state abolished these adverse effects (Boselie, Vancleef, Smeets, & Peters, 2014) In addition, Howell conducted hope based group therapy with 24 i ndividuals with chronic pain. After a six week intervention, the authors found that participants experienced significant improvements in well being and pain acceptance (Howell, Jacobson, & Larsen, 2014) Taken together, therapies aimed at enhancing resilience may serve a s a potential target for pain management. Despite this possibility few studies have examined the impact of resilience interventions in individuals with persistent pain, and there have been none to our knowledge that have exami ned these relationships in TM D. Therefore, the primary objective s of this pilot study w ere to investigate the association between hope and cortisol and examine differences in pain evoked cortisol levels between TMD participants receiving a resilience based hope intervention compared to participants in a pain education control group. Given evidence of heightened stress evoked cortisol levels in TMD, as well as the protective effects of positive psychological states, it was hypothesized that cortisol would be lower in the Hope group (wh en compared to Pain Education) after the induction of a pain stressor (i.e., cold water task). METHODS Participants Individuals with TMD were selected through flyers and radio advertisements placed in the community. Participants were included if they: 1) reported moderate orofacial pain ( > 3/10 on a pain rating scale) during the past six months, 2) experienced pain on at least 15 days during the past month, and 3) met diagnostic criteria for TMD. Exclusionary criteria included age <18 or >65 years, current use of opioid analgesics, and diagnosis of neurological, neuroendocrine, and/or cardiovascular disorders. Procedures The University of Florida Institutional Review Board approved of all procedures and participants provided informed consent before enrolli ng into the study. Due to diurnal variation in cortisol, all testing sessions were scheduled at approximately the same time of the day within participants (between 08:00 and 10:00 am ). Study procedures involved attendance at three intervention sessions and two experimental sensory pain testing sessions (pre and post intervention), for a total of five visits. At the first visit, health history and demographic information were collected, questionnaires were completed, and a diagnostic examination (DC/TMD) wa s carried out for assessment of TMD symptoms. Classification of TMD involved applying pressure to the orofacial region (i.e., temporomandibular joint and muscles of the temporalis, masseter, and posterior mandibular sites). For study inclusion, participan ts were required to report pain either in the joint or one orofacial muscle in response to palpation. Participants then underwent the following sensory pain procedures: heat pain tolerance, heat temporal summation, mechanical pressure pain threshold, cutan eous pressure pain, and cold pain threshold/tolerance. Cortisol saliva samples were taken a total of two times during the experimental sessions: before the start of sensory testing and 30 minutes after the cold pressor task. After the initial laboratory se ssion, participants were randomized to either a Hope based resilience intervention or Pain Education, whereby they received 3 weekly 1 hour sessions (Visits 2 4). During the final visit (Visit 5), sensory pain testing was repeated. After study completion, participants were provided an honorarium up to $200. Psychosocial Intervention Protocols Hope Intervention. The development of the Hope intervention protocol was based upon a theoretical model of hope posited by Charles Snyder (Snyder et al., 1991) Hope achieve goals (pathways thinking), an d sustain focused energy toward successful attainment of goals (agency). A general outline of each Hope inte rvention session is as follows: Session 1) discuss personal history of TMD, overview of conceptual framework of hope: cultivating goal directed thinking, developing routes to achieve goals (pathways thinking), enhancing motivation for successful goal attai nment (agency); Session 2) discussion of pathways thinking, fostering positive thinking, identification of personal strengths; Session 3) discussion of agency thinking, goal focused imagery exercise, review concepts and skills learned, provide feedback on the use of hope concepts for pain management.
E XAMNING THE I MPACT A R ESILIENCE B ASED H OPE I NTERVENTION ON P AIN E VOKED C ORTISOL R ESPONSE University of Florida | Journal of Undergradua te Research | Volume 1 9 Issue 2 | Spring 201 8 3 Skills building activities were conducted during the session and at home to facilitate hopeful thinking and goal directed behavior. Pain Education Intervention. A general outline of each Pain Education interv ention session is as follows: Session 1) discuss personal history of TMD, instruction on TMD symptoms, etiology, and treatments, information on Gate Control theory of pain; Session 2) education on the influence of stress on TMD pain; Session 3) discuss lif estyle management of pain (i.e., sleep hygiene, exercise), review concepts and skills learned. Questionnaires Adult Dispositional Hope Scale (ADHS): The Adult Dispositional Hope Scale (Snyder et al., 1991) is a self report, 12 item inventory designed to tap dispositional (trait) hope in adults, ages 15 and older. It consists of 4 agency, 4 pathway, and 4 distracter items. Responses to items are on a scale from 1 (defi nitely false) to 8 (definitely true). Agency and pathways subscale scores are derived, as well as a total score consisting of a sum of these two subscales (Range: 8 to 64). The ADHS was administered at the beginning of the baseline visit. Adult State Hope Scale (ASHS): The Adult State Hope Scale (Snyder et al ., 1996) is a self report, 6 item inventory used to assess goal directed thinking at a given moment in time. It consists of 3 agency and 3 pathway items. Responses to items are on a scale from 1 (definitely false) to 8 (definitely true). Agency and path ways subscale scores are obtained, as well as a total score consisting of a sum of these two subscales (Range: 6 to 48). The ASHS was administered to participants during baseline and Visit 5 sessions immediately prior to sensory pain testing. Pain Inducti on Cold Pressor (CP). During the pre and post intervention experimental sessions, participants submerged their dominant hand up to their wrist in 5 C water until they were no longer able to tolerate the cold water pain (for a maximum immersion of three intensity ratings at threshold and tolerance and the time participants first reported pain and withdrew their hand was recorded (data reported elsewhere). The CP task is a widely used procedure to assess pain sensitivity (Herbert et al., 2014) Cortisol Assessment Cortisol was measured through saliva samples as salivary assessment is non invasive, cost effective, reliable, and easy to collect (Gann, Giovanazzi, V an Horn, Branning, & Chatterton, 2001) Participants had to refrain from alcohol use 12 hours before collection, eating one hour prior to collection, and brushing their teeth 45 minutes before collection to prevent salivary contamination. Participants f irst pooled saliva in their mouth and then passively salivated into a 2 inch straw attached to a plastic test tube until 2 mL of saliva was obtained. Samples were refrigerated within two hours after collection and then later kept in a 80 C freezer. Sampl es were shipped overnight on dry ice to Salimetrics LLC for testing of cortisol levels (Salimetrics, 2015) On the day the samples were to be assayed, they were thawed to room temperature, vortexed, and then centrifuged for 15 minutes at approximately 3,000 RPM (1,500 x g). Samples were tested for salivary cortisol (Cat. No. 1 3002) using high sensitivity enzyme immunoassays. The test used determination and had an assay range of .012 3 ug/dL. The average intra assay coefficient of variation was 7.0%, the inter assay coefficient of variation was 8.0%, and the assay sensitivity was 0.007 ug/dL. Per Salimetrics, acceptance criteria for duplica te results was a coefficient of variation < 15% between samples 1 and 2. Statistical Analysis Statistical analyses were completed using SPSS 23.0 (SPSS Inc, Chicago, IL). Before conduc ting analyses, distributions of the variables were examined and extreme cortisol outliers (3 SD above or below the mean) were eliminated. Bivariate correlations were conducted to examine associations between state and trait hope (using total scores and subscale scores) with baseline and pain evoked cortisol levels The followi ng guidelines were implemented to assess the strength of the correlation coefficient: small ( r =.10 to .29), medium ( r =.30 to .49), large ( r =.50 to 1.0). To examine the effect of intervention group on pain evoked cortisol levels, a 2 (Intervention Group) x 2 (Time: Pre vs. Post Intervention) repeated measures ANOVA was conducted. Follow up mean comparisons to significant F tests were conducted using Fisher Least Significant Difference tests. To obtain effect size estimates associated with F tests, partial e ta squared ( p 2 ) was calculated from GLM analyses (small=.01, medium=.06, large=.14) Significance was set at p < .05 (two tailed). RESULTS Participant Characteristics Demographic and clinical characteristics of the participant sample are shown in Table 1. The majority of the participants were female, not married non Hispanic, white/Caucasian, and either employed full or part time with a college education. Age s ranged from 19 62 years
N ADIA H OSSAIN MICHAEL ROBINSON ROGER FILLINGIM & E MILY B ARTLEY University of Florida | Journal of Undergraduate Research | Volume 1 9 Issue 2 | Spring 201 8 4 (mean=39 years) and duration of TMD pain was 0.25 30 .0 years (mean=9.7 years). There were no significant differences in demographic or clinical characteristics across intervention group s Thirty six participants signed consent to particip a te during Visit 1, but 1 subject was excluded due to hypertension. Before randomization, 2 more participants withdrew consent due to time commitments and exacerbation of TMD pain. From the remaining 33 randomized participants, 1 participant discontinued f rom the Hope group (i.e., moved) and 3 participants withdrew from the Pain Education group (i.e., 1 moved, 2 lost to follow up) before the completion of the study. Thus, 29 participants completed all five sessions of the study (Hope: N =15). Baseline saliva samples from 1 participant had blood contamination, and 2 participants experienced xerostomia during saliva collection; therefore, these samples were excluded from analysis. Further, 1 participant (Hope Group) had a hormone value that was an extreme outli er at pre intervention resulting in the exclusion of this observation. Table 1. Demographic and Clinical Characteristics across Intervention Group Associations between Hope and Cortisol The relationship between hope (as measured by the dispositional and state hope scales) and cortisol levels (measured at baseline and pain evoked) was investigated using Pearson product moment correlation coefficients. There were strong, negative correlatio n s between dispositional pathways thinking ( r = .5 1 p =.00 6 ) dispositional agency ( r = 43 p =.0 2 ) and dispositional hope (total scale) ( r = .57, p =.001) with baseline cortisol at post intervention, contributing 19 33% of the variance in cortisol levels. Fu r ther, greater situational pathways thinking at pre intervention was negatively correlated with baseline cortisol levels at post intervention ( r = .50, p <.01), explaining 25% of the variance in cortisol levels. All other correlations were non significant ( r .36, p Findings for the total dispositional scale and situational pathways scale are provided in Figures 1 and 2. Differences in Cortisol across Intervention Group and Time Descriptive data for cortisol levels are presented in Table 2. There were no significant differences across group (Hope vs. Pain Education) in mean levels of baseli ne cortisol either before or after the intervention period [ F (1, 25)= .76, p =.39, p 2 =.03], suggesting that the two groups had similar cortisol levels prior to the cold pressor test For pain evoked cortisol levels, t he main effects of intervention group [ F (1, 21)= .34, p =.56, p 2 =.02] and time [ F (1, 21)= .01, p =.91, p 2 =.00] were not significant. Further, the Group X Time interaction was non significant [ F (1, 21)= .58, p =.45, p 2 =.03] indicating that there were no intervention group differences from pre to post intervention in pain evoked cortisol levels Figure 1. Relationship between dispositional hope and cortisol. Higher trait hope was associated with lower levels of basal cortisol at post intervention Figure 2. Relationship between situational hope and cortisol. Greater situational pathways thinking during pre intervention was associated with lower baseline c ortisol at post intervention.
E XAMNING THE I MPACT A R ESILIENCE B ASED H OPE I NTERVENTION ON P AIN E VOKED C ORTISOL R ESPONSE University of Florida | Journal of Undergradua te Research | Volume 1 9 Issue 2 | Spring 201 8 5 Table 2. Descriptive Statistics for Cortisol Levels (ug/dL) across Intervention Group and Time DISCUSSION While evidence supports the relationship between resilience and adaptive pain functioning, there have been no studies examining the therapeutic efficacy of resilience on pain related physiological activity. Therefore, the primary objectives of this pilot s tudy were to examine the association between cortisol and hope (a measure of resilience), and assess whether individuals undergoing a resilience based hope intervention exhibit a stronger change in pain evoked cortisol response, compared to participants un dergoing pain education. We found that that higher dispositional hope and situational pathways thinking (at pre intervention) were associated with lower baseline cortisol levels at post intervention. These findings suggest that hope may serve as a protect ive factor against heightened HPA activity and would align with existing research supporting the biological benefits of resilience. For instance, Lai and colleagues observed that individuals who scored higher in optimism secreted less salivary cortisol (Lai et al., 2005) while another study found that optimism was protective against elevated cortisol secretion on days of high perceived stress (when compared at the within person level) (Job in, Wrosch, & Scheier, 2014) Similarly, Polk et al. found divergent effects between positive (PA) and negative affect (NA) lower cortisol levels were associated with PA while higher cortisol concentrations were related to NA (Polk, Cohen, Doyle, Skoner, & Kirschbaum, 2005) Overall, these studies suggest that posit ive psychological states may modulate adrenocortical functioning. Following the intervention, both the Hope and Pain Education groups showed similar pain evoked cortisol activity. Although this is in contrast to existing research observing alterations in cortisol after psychosocial intervention (Matousek, Dobkin, & Pruessner, 2010; Robinson, Garofalo, & Gatchel, 2006; Yoo et al., 2016) our findings are comparable to Goodin and colleagues, who reported that brief (2 session) hypnosis produced negligible effects on cortisol reactivity to experimentally induced pain (Goodin et al., 2012) While it is unclear why we were unable to detect group differences, it is important to note that our intervention period was relatively brief; thus, a larger activity and observe differential effects at the group level. Findings may have also been due to cortisol decreasing after the baseline period. Indeed, after additional analysis results revealed sign ificant reductions in cortisol from the baseline to pain evoked period ( p =. 02 p 2 =. 20) which could have created a floor effect and attenuated group differences. Another possible explanation for the lack of findings across interventions was our assessment of cortisol. Specifically, it has been suggested that measures of recovery (rather than response parameters) may better characterize system functioning, such that faster recovery after the onset of a stressor reflects an adaptive process (Chapman, Tuckett, & Song, 2008) Th erefore, it is conceivable that group differences may have emerged in cortisol recovery (e.g., taking multiple cortisol measurements after pain induction) that were not accurately reflected in the single measurement. Future studies would benefit from exami ning whether resilience based interventions impact recovery parameters in physiological pathways associated with pain. Strengths and Limitations Some limitations merit acknowledgement. First, given the pilot nature of this study, our current sample size may have been underpowered to detect small effect group differences. Additionally, only 4 out of 36 correlations were significant when examining th e association between hope and cortisol and it is unclear whether results would replicate in a larger sample Findings should therefore be interpreted with caution. Second, study participants were primarily Caucasian, female, and college educated thus, t he generalizability to other demographic groups is unclear Cortisol was measured 30 minutes after the cold pressor task to remain consistent with previous research (Dickerson & Kemeny, 2004; Goodin et al., 2012) However, other studies have taken samples at later time points (DeSantis, Adam, Hawkley, Kudielka, & Cacioppo, 2015; Gaab et al., 2003) after a stressor was administered ; therefore, it is possible that cortisol may have peaked at a su bsequent time point and impacted the ability to detect differences. Finally, we delivered a brief (3 session) intervention to participants to reduce the burden associated with longer treatment. As a result, it is uncertain whether a longer intervention dur ation would have produced more robust effects. Despite these limitations, the current study is one of few that have evaluated the contributions of a resilience based treatment for chronic pain, and intervention development was based upon an existing theoretical model of hope (Snyder et al., 1991) Retention rates were high for the study, with a lower dropout rate observed for the Hope group, thus speaking to the feasibility and credibility of the interventions. Furthermore, this is the first randomi zed controlled trial to assess the physiological effects of a resilience oriented intervention, and the findings add to the literature on the role of hope on neuroendocrine functioning.
N ADIA H OSSAIN MICHAEL ROBINSON ROGER FILLINGIM & E MILY B ARTLEY University of Florida | Journal of Undergraduate Research | Volume 1 9 Issue 2 | Spring 201 8 6 C ONCLUSION Although preliminary, results indicate that individuals higher in hope had lower baseline cortisol levels; however, there were no intervention group differences in pain evoked cortisol response. Given the limited research in this area, continued investigation is warranted to identify resilience factors associa ted with adaptive physiological functioning, as well as examine whether larger scale resilience interventions impact physiological processes associated with pain and stress. ACKNOWLEDGMENTS Research reported in this publication was supported by the Ameri can Pain Society, Sharon S. Keller Chronic Pain Research Grant awarded to Dr. Emily J. Bartley. 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GRANT OF PERMISSIONS In reference to the following title: "#$%#!&'((#%) *+#,%)%)-!./0!1,2#3.!'4!#!50(%6%0)30 7 8#(0$!&'20!1).09:0).%')! ')!;#%) 7 *:'<0$!='9.%('6!50(2')(0 ! >)%:09(%.?!'4!@6'9%$#A! !"#$%&'(")(*%+,$-$&+#&.,(/,0,&$12 B ! I, Nadia Hossain as copyright holder or licensee with the authority to grant copyright permissions for the aforementioned title(s), hereby authorize the University of Florida, acting on behalf of the Board of Trustees of the University of Florida to digitize, distribute and archive the title(s) for nonprofit, educational purposes via the Internet or successive technologies. This is a non exclusive grant of permissions for on line and off line use for an indefinite term. Off line uses shall be consistent either, for educational uses, with the terms of U.S. copyright legislation's "fair use" provisions or, by the University o f Florida, with the maintenance and preservation of an archival copy. Digitization allows the University of Florida to generate image and text based versions as appropriate and to provide and enhance access using search software. This grant of permission s prohibits use of the digitized versions for commercial use or profit. 4/2/18 Signature of Copyright Holder Date of Signature Nadia Hossain Printed or Typed Name of Copyright Holder Attention : Digital Services / Digital Library Center Smathers Libraries Universit y of Florida P.O. Box 11700 3 Gainesville, FL32611 700 3 P: 352.273.2900 DLC@uflib.ufl.edu Form: http://digital.uflib.ufl.edu/pr ocedures/copyright/GrantofPermissions.doc