Increased Pain Variability in Patients With Chronic Pain: A Role for Pain Catastrophizing.

Pain is an inherently negative perceptual and affective experience that acts as a warning system to protect the body from injury and illness. Pain unfolds over time and is influenced by myriad factors, making it highly dynamic. Despite this, statistical measures often treat any intraindividual variability in pain ratings as noise or error. This is consequential, especially for research on chronic pain, because pain variability is associated with greater pain severity and depression. Yet, differences in pain variability between patients with chronic pain and controls in response to acute pain has not been fully examined-and it is unknown if dispositional factors such as pain catastrophizing (negative cognitive-affective response to potential or actual pain in which attention cannot be diverted away from pain) relate to pain variability. In the current study, we recruited chronic-pain patients (N = 30) and pain-free controls (N = 22) to complete a 30-second thermal pain task where they continually rated a painful thermal stimulus. To quantify pain variability and capture potential dynamics, we used both a traditional intraindividual standard deviation (iSD) metric of variability and a novel derivatives approach. For both metrics, patients with chronic pain had higher variability in their pain ratings over time, and pain catastrophizing significantly mediated this relationship. This suggests patients with chronic pain experience pain stimuli differently over time, and pain catastrophizing may account for this differential experience. PERSPECTIVE: The present study demonstrates (using multiple variability metrics) that chronic pain patients show more variability when rating experimental pain stimuli, and that pain catastrophizing helps explain this differential experience. These results provide preliminary evidence that short-term pain variability could have utility as a clinical marker in pain assessment and treatment.

Prevalence of Anxiety as a Variable in Treatment Outcomes for Individuals With Chronic Refractory Cough.

PURPOSE: Anxiety is a mental state characterized by an intense sense of tension, worry, or apprehension relative to something adverse that might happen in the future. Anxiety is a known comorbidity in cough patients, yet its prevalence among those with chronic refractory cough (CRC) is unknown. Anxiety is not typically assessed during evaluation for CRC, but treatments for CRC such as neuromodulators and behavioral cough suppression therapy (BCST) may potentially attenuate anxiety. This preliminary study investigates the potential prevalence of anxiety in CRC and its possible role in treatment outcomes. METHOD: CRC patients seen in a specialty clinic at the University of Utah or the University of Montana completed the Leicester Cough Questionnaire (LCQ) pre- and post-BCST treatment. Participants were dichotomized into positive anxiety screen (PAS) and negative anxiety screen (NAS) groups based on presence or absence of documented anxiety within electronic medical records at the University of Utah and based on a Generalized Anxiety Disorder-7 score > 5 at the University of Montana. RESULTS: Of the 86 total participants, 37 (43%) were in the PAS group (29 females, Mage = 56 ± 13) and 49 (57%) were in the NAS group (36 females, Mage = 64 ± 14). Eighty-nine percent of CRC participants with a PAS reported a clinically meaningful improvement in LCQ total score following treatment compared to 65% of NAS participants. Furthermore, mean pre- to posttreatment change scores on the LCQ were significantly greater within the PAS group (p = .002, Cohen's d = 0.7, indicating a moderate to large effect size). CONCLUSION: This preliminary study suggests that (a) anxiety may be prevalent among those with CRC and (b) those patients who screen positive for anxiety report greater benefit from BCST.

Moment-to-moment relationships between pain, fatigue, and distress as a function of GI symptoms in fibromyalgia.

OBJECTIVE: There is emerging evidence that people with both fibromyalgia and functional gastrointestinal (GI) disorders report more severe psychological symptoms than people with only fibromyalgia or a functional GI disorder. We use Ecological Momentary Assessment (EMA) to examine whether, for people with fibromyalgia, accompanying GI symptoms result in stronger bidirectional relationships between distress and bodily pain or fatigue. METHODS: Participants were 67 women with fibromyalgia from a study by Okifuji et al. (2011; 13), in which EMA data on pain, fatigue, and distress was collected over 30 days. Thirty-three participants reported GI symptoms at baseline, and 34 participants reported no GI symptoms but at least one other bodily symptom. Using multilevel linear regressions with interaction terms, we compared the two groups on the strength of reciprocal within-day and day-to-day relationships between pain, fatigue, and distress. RESULTS: GI symptom status did not moderate relationships between distress and pain. However, participants with GI symptoms uniquely reported more distress following increased fatigue within days (b = 0.120, 95%CI: 0.041,0.198), and sharper distress escalations across days (b = 0.078 95%CI: 0.007, 0.149). CONCLUSION: We do not find evidence of stronger bidirectional within-day and day-to-day relationships between distress and bodily symptoms in this patient group. We do, however, find evidence of heightened fatigue-related distress and escalating distress. These cyclical processes can become a focus for cognitive behavioural therapy, patient education, and physical (exercise/sleep) therapy aimed at addressing fatigue.

Cluster analysis to identify patient profiles and substance use patterns among pregnant persons with opioid use disorder.

The study objective was to identify distinct profiles of pregnant persons with opioid use disorder (PP-OUD) using cluster analysis and examine difference in substance use patterns between profiles. We examined data from 104 PP-OUD ≤ 32 weeks of gestation who were recruited into a behavioral health clinical trial at two academic medical centers. We used Partitioning Around Medoids analysis to identify clusters and explored patterns of substance use and substance use treatment between clusters using bivariate statistical tests and regression methods. We identified two distinct clusters of participants, including 'Group A' (n = 68; 65.4 %) and 'Group B' (n = 36; 34.6 %). Group A had fewer members who were not employed (38 % vs 58 %) and incarcerated (3 % vs 8 %) compared to Group B. Group A compared with Group B included more members with: a history of overdose (72 % vs 50 %); anxiety (85 % vs 25 %); ≥moderate pain (76 % vs 22 %); ≥moderate depression (75 % vs 36 %); ≥moderate drug use severity (94 % vs 78 %); and, more days of cannabis (mean: 6.2 vs 2.3 days), stimulant (mean: 4.5 vs 1.3 days), and injection heroin (mean: 1.3 vs 0 days) use in the past 30 days (P < 0.05 for all comparisons). Clusters of PP-OUD differed with respect to sociodemographic characteristics, mental health conditions, and substance use patterns. More research is needed to confirm identified profiles and assess treatment outcomes associated with cluster membership.

Exploring the sex differences in conditioned pain modulation and its biobehavioral determinants in healthy adults.

BACKGROUND: Females are at greater risk of chronic pain, and exhibit higher pain sensitivity compared to males. However, sex differences in conditioned pain modulation (CPM), a neurophysiological risk factor of chronic pain, are unclear. CPM is influenced by many factors, some of which are sex-dependent. This study explored the sex differences in CPM and its biobehavioral determinants, such as blood pressure responses, physical activity levels, pain catastrophizing scores, and conditioning stimulus intensity, in young, healthy, physically active males and females. METHODS: Twenty-six males and 24 females completed the CPM test using an electrical pain stimulus and a cold pain stimulus induced via 2 min of cold pressor test. Blood pressure was assessed at baseline and during cold pressor test, whereas cold pain ratings were obtained during cold pressor test to monitor the conditioning stimulus intensity. Physical activity was evaluated via questionnaires and accelerometer, whereas pain catastrophizing was evaluated via a questionnaire. RESULTS: Both males and females exhibited CPM, without sex differences in the magnitude of CPM. The males showed higher resting blood pressure, higher physical activity levels, and lower pain catastrophizing scores than the females, without sex differences observed in cold pain ratings and proportion of those who met the physical activity guidelines. No correlations were observed between CPM and its determinants. CONCLUSIONS: The results suggest the complexity of mechanisms underlying the sex differences in CPM. The sex differences in CPM, along with its determinants, may need to be examined in individuals with some risk factors for chronic pain.

Mediating role of physical activity in the relationship between exercise-induced muscle pain and symptom severity in women with fibromyalgia.

BACKGROUND: Individuals with fibromyalgia (FM) exhibit generalized hyperalgesia to pain stimuli, and physical activity (PA) is critical to manage FM symptoms. PURPOSE: This study examined the relationship between exercise-induced muscle pain, symptom severity, and PA in 28 women with FM. METHODS: Muscle pain rating (MPR) was assessed during 3 minutes of submaximal isometric handgrip exercise, whereas PA and symptom severity were evaluated via self-report questionnaires. The analysis examined the relationship between the variables, with the specific interest in the mediating role of PA in the relationship between exercise-induced muscle pain and symptom severity. RESULTS: MPR was positively associated with symptom severity (b = 1.89; 95% CI = 0.01, 3.76; P = .048) and inversely associated with PA levels (b = -0.16; 95% CI = -0.30, -0.03; P = .021). PA levels were inversely associated with symptom severity (b = -7.94; 95% CI = -12.46, -3.42; P = .001). After statistically controlling for PA levels, the relationship between MPR and symptom severity was no longer significant (b = 0.60; Wald 95% CI = -1.05, 2.25; P = .474). CONCLUSION: Results show the link between the variables, and specifically demonstrate that PA mediates the relationship between exercise-induced muscle pain and symptom severity.

Prediction of pain responses to subsequent cold pressor test via baseline heart rate variability in healthy adults.

BACKGROUND: Baseline heart rate variability (HRV) that reflects parasympathetic nervous system (PNS) activity may serve as an objective, physiological index of pain assessment, but more research is warranted to examine the link between HRV and laboratory pain responses. This study examined whether baseline HRV would predict pain responses to subsequent cold pressor test (CPT) in healthy adults. METHODS: One hundred twenty-three participants completed resting HRV assessment and CPT consisting of immersing their right hand into a cold-water bath for a maximum of 2 min. Pain threshold and pain rating were assessed during CPT. Completion status of CPT, defined as completing CPT or terminating CPT before 2 min, was recorded as an additional laboratory pain measure. Pearson's correlation analysis was performed to examine the link between HRV and pain responses, whereas regression analysis was performed to test the prediction of pain responses via baseline HRV. RESULTS: HF-HRVlog , which reflects PNS activity, was significantly associated with the CPT completion status (r = 0.23, p = 0.01), but not significantly associated with pain threshold (r = 0.17, p = 0.06) or pain rating (r = -0.11, p = 0.24). HF- HRVlog was found to be a significant predictor of CPT completion status (B = 0.53, p = 0.013). CONCLUSIONS: Baseline HF- HRVlog may serve as an objective, physiological index to predict laboratory pain responses, and the completion status of laboratory pain tests, such as CPT, may be used as a laboratory pain measure to capture important individual differences in pain processing. SIGNIFICANCE: A better understanding of how psychophysiology relates to human pain is important. We examined the association of baseline heart rate variability (HRV) with pain response to subsequently-administered cold pressor test (CPT) in healthy adults. We found that HF-HRVlog , which reflects parasympathetic nervous system activity, predicted the completion status (completion or termination) of CPT. Baseline HF-HRVlog may serve as an objective, physiological index of pain and the completion status of CPT may help assess the important individual differences in pain processing.

Addressing opioid medication misuse at point of service in community pharmacy: A study protocol for an interdisciplinary behavioral health trial.

BACKGROUND: >1 in 3 of the 9 million individuals engaged in opioid medication misuse obtain legitimate opioid prescriptions and fill these in community pharmacies, which are subsequently misused. This study is testing the efficacy of a pharmacist-led intervention-Brief Intervention-Medication Therapy Management (BI-MTM)-compared to standard medication counseling (SMC) to address opioid medication misuse. METHODS: Design. This study is a single-blinded 2-group parallel randomized trial within 13 community pharmacies that will enroll 350 individuals. Participant Recruitment. Pharmacy staff approach patients and ask about interest in completing a brief confidential screening tool, which includes opioid medication misuse assessment. Interested patients who report misuse are asked to provide informed consent. Enrolled patients are assessed for behavioral and physical health at enrollment, 2-months post-enrollment, and 6-months post-enrollment. INTERVENTIONS: Following baseline assessment, participants are randomized (1:1 ratio) to: SMC, a medication information/counseling intervention or BI-MTM, an intervention comprised by 4 evidence-based components: medication therapy management, brief intervention, naloxone dispensing, and patient navigation. ANALYSES: Primary analyses involve estimating 3-level generalized linear mixed models to relate repeated assessments across time of opioid medication misuse (i.e., the Prescription Opioid Misuse Index) to the intervention. CONCLUSION: Study results will provide the first critical step towards integrating a highly accessible, low-cost approach to managing risks related to opioid use. Community pharmacies provide an incredibly important setting in which patients can receive high quality care to support health behavior change. Successfully completing this project sets the stage for a large-scale effectiveness study. (NCT#: NCT05141266).

Pain Severity and Interference and Substance Use Among Community Pharmacy Patients Prescribed Opioids: A Secondary Analysis of the PHARMSCREEN Study.

This secondary analysis examined relationships between pain severity and interference and substance use among patients filling opioid prescriptions in Indiana and Ohio community pharmacies (n = 1,461). We likewise sought to explore the moderating role of gender in pain-substance use relations. We used patient-reported data from a cross-sectional health survey linked with controlled substance dispensing data from statewide prescription drug monitoring programs. Multivariable logistic regression estimated associations between pain severity and interference and various indices of risky prescription opioid use and non-opioid substance use. Exploratory analyses examined whether gender moderated associations. Increased pain severity was associated with increased odds of moderate- to high-risk opioid use (OR: 1.23; 95% CI: 1.16-1.31) and opioid-benzodiazepine co-use (OR: 1.20; 95% CI: 1.03-1.40). Increased pain interference was associated with greater odds of receiving opioids from multiple pharmacies or providers (OR: 1.15; 95% CI: 1.01-1.31). Increased pain severity and interference were associated with higher odds of any tobacco use (severity: OR: 1.13; 95% CI: 1.06-1.21; interference: OR: 1.07; 95% CI: 1.01-1.12) and weekly to daily sedative use (severity: OR: 1.13; 95% CI: 1.03-1.25; interference: OR: 1.13; 95% CI: 1.04-1.22). Increased pain severity was associated with decreased odds of any alcohol use (OR: 0.93; 95% CI: 0.88-0.99). Gender was a significant effect modifier in associations between pain and alcohol, tobacco, and cannabis use. The study was registered in the database of clinicaltrials.gov (register number NCT03936985). Perspective: This study suggests that pain severity and interference are associated with increased use of non-medical prescription opioids, sedatives, and tobacco and decreased use of alcohol, in ways that are different between women and men. Findings may guide the development of gender-sensitive evidence-based strategies to ameliorate or prevent substance misuse among patients living with pain.

Pregnancy and the Opioid Crisis: Heightened Effects of COVID-19.

The opioid epidemic continues to affect pregnant women with opioid use disorder adversely in unique and enduring ways. The onset of the coronavirus disease 2019 (COVID-19) pandemic and the necessary public health measures implemented to slow the transmission have increased barriers to care for these same women. This commentary explores the implications of these measures and discusses strategies we have developed to manage these challenges based on our work in a clinical trial providing patient navigation to pregnant mothers with OUD. We believe these solutions can be applied in medical, behavioral health, and research settings through the pandemic and beyond to increase the quality of care and resources to this vulnerable population.

The visual time analog scale: simple, novel measurement approach to assess pain in patients with chronic pain.

Aim: We conducted a preliminary evaluation of a newly developed, time-based visual time analog (VITA) scale for measuring pain in chronic pain patients. Materials & methods: 40 patients with chronic back pain rated their pain over four visits using numerical (pain) rating scale (NRS) and VITA assessing pain intensity by distributing the amount of time spent on 'not aware of pain' (blue), 'aware of nothing but pain' (red) and time in between (yellow). Results: The NRS scores were correlated with the VITA Red but not with VITA Blue. The psychometric analyses revealed that VITA achieved greater reliability and sensitivity than did NRS. Conclusion: The results provide preliminary support for VITA scale for assessing pain intensity in patients with chronic pain.

Comparable conditioned pain modulation and augmented blood pressure responses to cold pressor test among resistance exercisers compared to healthy controls.

Conditioned pain modulation (CPM) test examines central pain inhibitory processing. Aerobically-trained individuals show greater CPM. However, there is a paucity of knowledge regarding CPM among resistance exercise-trained individuals, although regular engagement in resistance exercise may lead to greater CPM via augmented blood pressure (BP) responses during the CPM test. Therefore, the present study compared CPM and BP responses between resistance exercisers (REs) and controls (n = 15 per group). The participants completed the CPM test to evaluate changes in electrical pain ratings to the ankle after cold pressor test (CPT) consisting of immersing a hand into a cold water bath compared to baseline. REs and controls exhibited similar CPM, although REs showed greater systolic BP responses to CPT compared to controls. The results suggest that the role of BP in CPM is likely complex, and the role of exercise in central pain processing and cardiovascular system needs to be studied.

Prospective Association of Serum Opioid Levels and Clinical Outcomes in Patients With Cancer Pain Treated With Intrathecal Opioid Therapy.

BACKGROUND: Opioids remain the mainstay of cancer pain management but are associated with systemic toxicity. In refractory cancer pain, intrathecal therapy (ITT) is associated with improved pain control, reduced systemic side effects, and improved survival. It has been assumed that ITT decreases systemic serum opioid levels and their associated toxicity, but there are limited data to support this assumption. This study hypothesizes that serum opioid levels decrease with ITT. Secondary objectives include comparative measures of pain, bowel function, and other cancer-related symptoms. METHODS: Fifty-one cancer patients undergoing ITT for cancer pain were recruited in a prospective observational study. Daily oral morphine equivalency (OME) dose, serum opioid levels, Brief Pain Inventory (BPI), MD Anderson Symptom Inventory (MDASI), and a constipation questionnaire were obtained at the time of implant, and 4 and 8 weeks postoperatively. RESULTS: Average baseline daily OME was 375 mg (median, 240; interquartile range, 150-405; range, 0-3160), mean serum morphine concentration was 53.7 ng/mL (n = 17), and mean oxycodone concentration was 73.7 ng/mL (n = 20). At 4 weeks, 87.5% of patients had discontinued non-IT opioids, and 53% had undetectable (<2 ng/mL) serum opioid concentrations. At 8 weeks, 92% remained off all non-IT opioids and 59% had undetectable serum opioid levels. IT morphine doses >4.2 mg/d were invariably associated with detectable serum levels; with doses <4.2 mg, morphine was undetectable in 80% of subjects. IT hydromorphone doses >6.8 mg/d were detectable in the serum. Using linear mixed model analyses, there were statistically significant decreases in the mean "worst pain," "average pain," and MD Anderson symptom severity and interference scores at 4 and 8 weeks. This change was independent of serum opioid levels; when analyzed separately, there was no difference in the pain scores of subjects with detectable serum opioid levels compared to those with undetectable levels at 4 and 8 weeks. Constipation ranked as "quite a bit" or "very much" decreased from 58.7% to 19.2% of subjects at week 4 (P < .001) and to 37.5% at 8 weeks (P = .23). A very low complication rate was observed. CONCLUSIONS: ITT for cancer pain was associated with a marked reduction in serum opioid concentrations, with the majority of patients having undetectable serum levels. Reducing serum opioid concentrations in cancer patients may have implications with respect to restoring bowel function, improving fatigue, and promoting the integrity of antitumor immune function and warrants further study.

Opioid-related beliefs and prescription modalities for postoperative pain of Dutch and American physicians.

Aim: Opioid consumption and addiction are increasing worldwide, yet the USA stands out for its high addiction rates and opioid-related deaths. Considering that patient characteristics are comparable across western countries, physicians' prescribing modalities may influence opioid consumption. We conducted a pilot study to examine opioid-related beliefs and prescription habits of Dutch and American physicians. Methods & materials: A survey was administered to 488 physicians who routinely prescribe opioids for postoperative pain. Results: A total of 75 (16%) physicians responded to the survey. When deciding to prescribe opioids, Dutch physicians adopted a patient-guided approach, whereas most American doctors followed strict guidelines and protocols. Conclusion: This study identified significant differences between Dutch and American physicians' attitudes and prescribing modalities.

Update and future perspective of behavioral medicine in the treatment for chronic pain.

Chronic pain is a biopsychosocial condition, and behavioral medicine has made significant contributions to the understanding of the phenomenon and optimization of therapeutic outcomes. The objective of this article is to provide future perspectives of behavioral medicine in pain management based upon recent development in the field. We will briefly review the mainstream approach of cognitive-behavioral therapy, its variations and new and innovative approaches that are on the horizon. We also review strategies that address potential barriers to pain management. Behavioral medicine is a promising field in pain medicine. The future growth is likely to come from addressing how we incorporate the patient heterogeneity into our treatment approaches and a better understanding of its role in a multimodal treatment.

Tertiary Care Clinical Experience with Intravenous Lidocaine Infusions for the Treatment of Chronic Pain.

Objective: To evaluate the safety of and long-term pain relief due to intravenous lidocaine infusion for the treatment of chronic pain in a tertiary pain management clinic. Design: Retrospective chart review. Methods: Medical records were reviewed from 233 adult chronic pain patients who underwent one to three lidocaine infusions. The initial lidocaine challenge consisted of 1,000 mg/h administered intravenously for up to 30 minutes until infusion was complete, full pain resolution, the patient requested to stop, side effects (SEs) became intolerable, and/or if there were any safety concerns. Subsequent infusions were tailored to patient response. Data reviewed included pain diagnosis, lidocaine dose, SEs, and duration of pain relief documented at a follow-up visit. Results: Patients primarily had neuropathic pain (80%), were 94% white, 58% were female, and there was an average pain duration of 7.9 years. SEs were usually mild and transient, including perioral tingling, dizziness, tinnitus, and nausea/vomiting, and they were uncommon after the initial infusion. Overall, 41% of patients showed long-lasting pain relief, with positive response to the initial infusion associated with receiving and benefitting from subsequent infusions. Benefit by pain diagnoses varied from 32% to 58%. Conclusions: Our retrospective study in a heterogeneous population with chronic pain suggests that intravenous lidocaine is a safe treatment. Data also suggest long-term pain relief in a significant proportion of patients. Additional study is important in order to delineate patient selection, determine optimal dosing and treatment frequency, assess pain reduction and duration, and treatment cost-effectiveness.

Conditioned pain modulation among young, healthy, and physically active African American and non-Hispanic White adults.

OBJECTIVE: Research shows that African American (AA) adults experience more severe and frequent pain compared to non-Hispanic White (NHW) adults. Additionally, experimental studies demonstrate that AA adults exhibit less efficient central pain inhibition compared to NHW adults, which may partially explain the racial/ethnic disparities in pain. Evidence suggests that regular physical activity (PA) may help improve central pain inhibition, but research shows that AA adults engage in less PA, and are less likely to meet PA guidelines for health promotion compared to NHW adults. These observations suggest that PA levels may help better understand the racial/ethnic difference in central pain inhibition. Therefore, this study compared central pain inhibition and PA levels among AA and NHW adults. METHODS: Young and healthy participants were recruited on campus, and 27 AA and 27 NHW adults completed this study. Central pain inhibitory processing was assessed using conditioned pain modulation (CPM), where changes in electrical pain ratings were quantified during and after exposure to pressure pain compared to baseline. PA levels were assessed using self-report questionnaires and accelerometer. RESULTS: The participants were generally physically active, and most participants in both groups met the public recommendation of PA for health promotion. Electrical pain ratings were significantly reduced during and after exposure to pressure pain compared to baseline. There was no racial/ethnic difference in a magnitude of changes in electrical pain ratings. CONCLUSION: Young, healthy, and physically active AA and NHW adults exhibit similar CPM responses. Regular PA may help attenuate the racial/ethnic difference in CPM responses.

Activity rhythms and clinical correlates in fibromyalgia.

The primary aim of this study was to evaluate activity rhythms in fibromyalgia syndrome (FMS) and their association with FMS-related symptoms. We hypothesized that stronger and more consistent activity rhythms would be associated with reduced symptom severity and presentation in FMS. Two hundred ninety-two patients with FMS (mean age = 45.1 ± 11.1; 272 women) provided a 7-day actigraphy recording and responses to questionnaires addressing degree of pain, fatigue, mood, and physical impairment. Using a simple cosine model, we extracted Amplitude (activity range), Phi (time at maximum), Mesor (mean activity), and their variabilities (across days) from each participant's actigraphy. The clinical and actigraphic measures were operationally independent. There was a significant canonical relationship between activity rhythm parameters and clinical FMS measures (r = 0.376, R = 0.14, P < 0.001). The set of Mesor, Amplitude, and Phi activity parameters remained associated with clinical measures when controlled statistically for both demographics and activity variability (P < 0.001). Each activity parameter provided unique discrimination of the clinical set by multivariate test (P = 0.003, 0.018, and 0.007 for Amplitude, Phi, and Mesor, respectively). These results revealed that better pain, fatigue, mood, physical impairment, and sleep outcomes were associated with higher activity range and more rhythmicity (Amplitude), increased mean activity (Mesor), and with earlier timing of peak activity (Phi). Exploratory analyses revealed significantly worse sleep for individuals with low Amplitude and more delayed Phi.

Management of fibromyalgia syndrome in 2016.

Fibromyalgia syndrome is a chronic pain disorder and defies definitively efficacious therapy. In this review, we summarize the results from the early treatment research as well as recent research evaluating the pharmacological, interventional and nonpharmacological therapies. We further discuss future directions of fibromyalgia syndrome management; we specifically focus on the issues that are associated with currently available treatments, such as the need for personalized approach, new technologically oriented and interventional treatments, the importance of understanding and harnessing placebo effects and enhancement of patient engagement in therapy.