Opioid metabolism and drug-drug interaction in cancer.

Concomitant use of multiple drugs in most patients with cancer may result in drug-drug interactions (DDIs), potentially causing serious adverse effects. These patients often experience unrelieved cancer-related pain (CRP) during and after cancer treatment, which can lead to a reduced quality of life. Opioids can be used as part of a multimodal pain management strategy when non-opioid analgesics are not providing adequate pain relief, not tolerated, or are contraindicated. However, due to their narrow therapeutic window, opioids are more susceptible to adverse events when a DDI occurs. Clinically relevant DDIs with opioids are usually pharmacokinetic, mainly occurring via metabolism by cytochrome P450 (CYP). This article aims to provide an overview of potential DDIs with opioids often used in the treatment of moderate-to-severe CRP and commonly used anticancer drugs such as chemotherapeutics, tyrosine kinase inhibitors (TKIs), or biologics. A DDI-checker tool was used to contextualize the tool-informed DDI assessment outcomes with clinical implications and practice. The findings were compared to observations from a literature search conducted in Embase and PubMed to identify clinical evidence for these potential DDIs. The limited results mainly included case studies and retrospective reviews. Some potential DDIs on the DDI-checker were aligned with literature findings, while others were contradictory. In conclusion, while DDI-checkers are useful tools in identifying potential DDIs, it is necessary to incorporate literature verification and comprehensive clinical assessment of the patient before implementing tool-informed decisions in clinical practice.

Feasibility and pilot testing of a personalized eHealth intervention for pain science education and self-management for breast cancer survivors with persistent pain: a mixed-method study.

PURPOSE: Here, we describe the development and pilot study of a personalized eHealth intervention containing a pain science education program and self-management support strategies regarding pain and pain-related functioning in female survivors of breast cancer. First, we aimed to evaluate the eHealth intervention's acceptability, comprehensibility, and satisfaction; second, we aimed to assess its preliminary efficacy. METHODS: A mixed-method study design was used. Breast cancer survivors with persistent pain were recruited. After 6 weeks of engagement with the eHealth intervention, acceptability, comprehensibility, and satisfaction were measured quantitatively with a self-constructed questionnaire and described qualitatively using focus groups. A joint display was used to present the meta-interferences between data. Efficacy was assessed via mixed effects models with repeated measures (outcomes assessed at baseline, 6 weeks, and 12 weeks). RESULTS: Twenty-nine women with persistent pain after breast cancer surgery participated. Overall, the eHealth program was well received and experienced as easy to use and helpful. The eHealth intervention seems useful as an adjunct to comprehensive cancer aftercare. Efficacy estimates suggested a significant improvement in pain-related functioning, physical functioning, and quality of life. CONCLUSION: A personalized eHealth intervention appears valuable for persistent pain management after breast cancer surgery. A large controlled clinical trial to determine effectiveness, and a full process evaluation, seems warranted.

Returning to Work After Breast Cancer Surgery: A Randomised Controlled Trial on the Effect of Pain Neuroscience Education.

PURPOSE: The aim of this study was to investigate the effect of pain neuroscience education compared to biomedical pain education after breast cancer surgery on (1) work status, (2) time until work resumption, and (3) change in return-to-work expectations up to 18 months post-surgery. METHODS: Participants were randomly assigned to either pain neuroscience education (intervention group) or biomedical pain education (control group) in addition to a standard physical therapy program after surgery for breast cancer. The first four months following surgery, one to two physiotherapy sessions and three educational sessions were scheduled. After, two educational sessions and two physiotherapy sessions were held at six and eight months postoperatively. All outcomes were assessed at four, six, eight, 12 and 18 months postoperatively. RESULTS: At 12 months, in the intervention group, 71% of the women returned to work compared to 53% in the control group (18% points difference, 95%CI:-0.1 to 35;p = 0.07). At 18 months, the differences decreased to 9% points, 95%CI:-26 to 7;p = 0.35). Neither time until work resumption (p = 0.46) nor change in estimation of own ability to return to work up to 18 months postoperatively (p = 0.21) significantly differed between both groups. CONCLUSION: No significant differences were found regarding return to work outcomes between women receiving pain neuroscience education versus biomedical pain education after breast cancer surgery. Further research is warranted to explore the potential role of pain neuroscience education in return-to-work interventions following breast cancer surgery.

Establishing Minimal Clinically Important Differences in Quality of Life Measures in Opioid-Induced Constipation.

BACKGROUND & AIMS: Opioids have a role in chronic pain management. However, opioid-induced constipation may cause patients to skip or reduce opioid doses, leading to inadequate pain relief and negatively impacting quality of life. We sought to establish a minimal clinically important difference to understand whether changes in quality of life scores are of value to patients. METHODS: Integrated data from the double-blind, controlled, phase 3 COMPOSE-1 and COMPOSE-2 trials of naldemedine in chronic noncancer pain and opioid-induced constipation were used to determine minimal clinically important differences using Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires. Patients completed the questionnaires (5-point Likert scale; predose, Weeks 2, 4, and 12), kept a daily log of Bowel Movement and Constipation Assessment, and rated satisfaction at end of study. Minimal clinically important differences were computed using an anchor-based method with 6 anchors: 5 from the Bowel Movement and Constipation Assessment and 1 from patient satisfaction. Threshold values for each anchor were set to define responders versus nonresponders based on score definitions. Clinically meaningful cutoff values for changes in PAC-SYM and PAC-QOL scores were determined using receiver operating characteristic curves. RESULTS: Data from 1095 patients (549, naldemedine; 546, placebo) were analyzed. The area under the curve for the receiver operating characteristic curves (ranges, 0.719 to 0.798 for PAC-SYM and 0.734 to 0.833 for PAC-QOL) indicated that both instruments can discriminate responders and nonresponders for each anchor. PAC-SYM cutoff values ranged from -1.04 to -0.83; PAC-QOL cutoff values ranged from -0.93 to -0.82. CONCLUSIONS: Based on data derived from the anchor method, reductions in PAC-SYM and PAC-QOL scores of >1.0 in patients with chronic noncancer pain and opioid-induced constipation are clinically meaningful. CLINICALTRIALS: gov Registration: NCT01965158; NCT01993940.

Pain prevalence and characteristics in survivors of solid cancers: a systematic review and meta-analysis.

PURPOSE: The latest systematic review on the prevalence of pain in cancer survivors was published 5 years ago. The current review aims to provide an extended overview on the prevalence of pain, pain mechanisms, pain characteristics, and assessment methods in cancer survivors. METHODS: A systematic research was conducted on 17th of April 2020 using MEDLINE, Embase, Scopus, Web of Science, and Cochrane looking at studies from 2014 to 2020. Studies had to report pain prevalence rates in cancer survivors with a solid tumor who finished curative treatment at least 3 months ago. Methodological quality was assessed by two independent reviewers using the Joanna Briggs Institute quality appraisal tool. Characteristics of the included studies, participants and reported pain prevalence rates were extracted. The reported prevalence rates of the individual studies were pooled within a meta-analysis. Meta-regressions were performed to identify possible determinants of the pooled pain prevalence. RESULTS: After deduplication, 7300 articles were screened, after which 38 were included in the meta-analysis. Risk of bias was rated low in 26 articles and moderate in 12 articles. The pooled pain prevalence was 47% (95%CI 39-55), with a heterogeneity of 98.99%. CONCLUSION: This meta-analysis suggests that nearly half of cancer survivors report pain after completing curative treatment at least 3 months ago. However, substantial unexplained heterogeneity warrants cautious interpretation of these results. Meta-regression using cancer type, treatment location, pain measurement, and follow-up time as a covariate could not explain influencing factors explaining the high heterogeneity.

Management of chronic low back pain and the impact on patients' personal and professional lives: Results from an international patient survey.

OBJECTIVE: The objective of this study was to investigate the impact of chronic low back pain (CLBP) on patients' personal and professional lives, and management strategies applied to treat CLBP. METHODS: A 60-question survey was developed, and respondents from 16 countries with a self-reported physician's diagnosis of CLBP were recruited via an online market research survey panel. Respondents were stratified as having mild, moderate, or severe pain. Target sample sizes per country and for pain severity were set. Data were weighted according to the known population and prevalence of CLBP in each country and the number of respondents from that country. RESULTS: Results from 9642 CLBP patients indicated that almost a quarter of patients with severe CLBP report a psychological comorbidity. Prescription pain medications were more commonly used by patients with severe CLBP (56%) than those with mild (20%) or moderate (34%) CLBP. Among those with severe CLBP who had been prescribed pain medication, 58% were prescribed opioids, with 1 in 4 patients using opioids for more than 5 years. Patients were primarily managed by general practitioners/primary care physicians, physiotherapists, neurologists, or orthopedic surgeons. CLBP negatively impacted patients' daily activities, social lives, and work productivity. CONCLUSION: Chronic low back pain has pronounced effects on patients' personal relationships, ability to work, and daily living. Almost 1 in four patients with severe CLBP reported a psychological comorbidity. Adherence to guidelines appears inconsistent, which is noteworthy as a substantial subgroup of patients with severe CLBP had been prescribed opioid medication for more than 5 years. Improved education is required to support healthcare professionals (HCPs) in identifying and understanding the complex biopsychosocial needs of CLBP patients to optimize pain management and to encourage referral of CLBP patients to physiotherapists and psychologists.

Fibromyalgia position paper.

Fibromyalgia syndrome is one of the most common causes of chronic widespread pain, but pain accompanies a wide range of ancillary symptoms. To date, its aetiopathogenesis remains elusive, and diagnosis is exquisitely clinical, due to the lack of biomarkers or specific laboratory alterations in fibromyalgia patients. This position paper has the purpose to summarise the current scientific knowledge and expert opinions about the main controversies regarding fibromyalgia syndrome, namely: (i) fibromyalgia definition and why it is still not recognised in many countries as a distinct clinical entity; (ii) fibromyalgia severity and how to evaluate treatment outcome; (iii) how to treat fibromyalgia and which is a correct approach to fibromyalgia patients.

Diagnostic and therapeutic care pathway for fibromyalgia.

Early diagnosis and timely and appropriate treatments positively influence the history of fibromyalgia syndrome (FM), with favourable repercussions at clinical, psychological, social and economic levels. Notwithstanding, there are still significant problems with timeliness of diagnosis, access to pharmacological therapies - particularly to innovative ones - and appropriate and effective taking in charge of patients. All the aforementioned factors have a great impact on FM patients' quality of life. Indeed, even though the World Health Organisation recognised FM as a chronic condition in the International Classification of Diseases 10th edition (ICD-10), many countries still fail to recognise the syndrome, and this negatively influences the capability to appropriately protect and care for patients. This is the case in several European Countries. In Italy, a few Regions have started to put in place precise indications for people suffering from FM, aiming at the implementation of diagnostic-therapeutic pathways. The Diagnostic-Therapeutic Care Pathway (DTCP) provides an important tool to meet the needs of patients suffering from chronic diseases. They present the organisation of an integrated assistance network. This includes a seamless path for disease prevention, diagnosis and treatment, by means of cooperation among physicians and other healthcare professionals.

Effectiveness of perioperative pain science education on pain, psychological factors and physical functioning: A systematic review.

OBJECTIVE: To synthesize the evidence on the effectiveness of pain science education on pain, psychological factors and physical functioning in adults who underwent surgery. DATA SOURCES: A systematic literature search of English articles using PubMed/Medline, Embase, Web of Science Core Collection, and Cochrane Library. REVIEW METHODS: The search strategy was constructed as follows: (((pain) AND (education)) OR (pain education)) AND (surgery). Only controlled quantitative studies in adults reporting outcome(s) on pain, psychological factors and/or physical functioning were included. Risk of bias was assessed using the Cochrane risk of bias tools. P-values and corresponding effect sizes for interaction-effect (time × group) portrayed the difference in change over time between groups were of interest. The last search was conducted on February 28, 2021. RESULTS: Nine papers (n = 1078) were deemed eligible for this review. Two randomized controlled trials showed significant interaction effects. Breast cancer patients who had received one preoperative pain science education session showed a significant increase in postoperative pain compared to controls (P-value = 0.0394). Furthermore, psychological factors (pain catastrophizing and kinesiophobia) decreased in participants who had received pain science education before total knee arthroplasty, while this was not the case in the control group (P-value < 0.001, ƞ2p:0.11). CONCLUSIONS: Overall, pain science education did not result in any significant postoperative effects on pain, psychological factors and/or physical functioning compared to controls. There is currently no strong evidence for the implementation of pain science education in the perioperative period.Registration number: PROSPERO: ID 161267, registration number CRD42020161267.

Cortisol and Subjective Stress Responses to Acute Psychosocial Stress in Fibromyalgia Patients and Control Participants.

OBJECTIVE: Hypothalamic-pituitary-adrenal axis dysfunction may play a role in fibromyalgia (FM) pathogenesis but it remains understudied in this disorder. Furthermore, early childhood adversities (ECA) are common in FM, but whether they moderate stress reactivity is unknown. Hence, we investigated cortisol and subjective responses to acute psychosocial stress in FM and controls, while adjusting for ECA. METHODS: Twenty-seven female FM patients and 24 age-matched female controls were recruited in a tertiary care center and through advertisements, respectively. The Childhood Trauma Questionnaire was used to measure ECA history. Salivary cortisol levels and subjective stress ratings were measured at multiple time points before and after the Trier Social Stress Test (TSST) was administered. RESULTS: Significant main effects of group [F(1,43) = 7.04, p = .011, lower in FM] and ECA [F(1,43) = 5.18, p = .028, higher in participants with ECA] were found for cortisol responses. When excluding controls with ECA (n = 5), a significant group-by-time interaction was found [F(6,39) = 2.60, p = .032], driven by a blunted response to the stressor in FM compared with controls (p = .037). For subjective stress responses, a significant main effect of group [F(1,45) = 10.69, p = .002, higher in FM] and a trend toward a group-by-time interaction effect [F(6,45) = 2.05, p = .078, higher in FM 30 minutes before and 30 and 75 minutes after the TSST, and impaired recovery (difference immediately after - 30 minutes after the TSST) in FM] were found. CONCLUSIONS: Blunted cortisol responsivity to the TSST was observed in FM patients compared with controls without ECA. FM patients had higher subjective stress levels compared with controls, particularly at baseline and during recovery from the TSST. In FM patients, ECA history was not associated with cortisol or subjective stress levels or with responsivity to the TSST. Future research should investigate the mechanisms underlying hypothalamic-pituitary-adrenal axis dysregulation in FM.

Pain in pancreatic ductal adenocarcinoma: A multidisciplinary, International guideline for optimized management.

Abdominal pain is an important symptom in most patients with pancreatic ductal adenocarcinoma (PDAC). Adequate control of pain is often unsatisfactory due to limited treatment options and significant variation in local practice, emphasizing the need for a multidisciplinary approach. This review contends that improvement in the management of PDAC pain will result from a synthesis of best practice and evidence around the world in a multidisciplinary way. To improve clinical utility and evaluation, the evidence was rated according to the GRADE guidelines by a group of international experts. An algorithm is presented, which brings together all currently available treatment options. Pain is best treated early on with analgesics with most patients requiring opioids, but neurolytic procedures are often required later in the disease course. Celiac plexus neurolysis offers medium term relief in a substantial number of patients, but other procedures such as splanchnicectomy are also available. Palliative chemotherapy also provides pain relief as a collateral benefit. It is stressed that the assessment of pain must take into account the broader context of other physical and psychological symptoms. Adjunctive treatments for pain, depression and anxiety as well as radiotherapy, endoscopic therapy and neuromodulation may be required in selected patients. There are few comparative studies to help define which combination and order of these treatment options should be applied. New pain therapies are emerging and could for example target neural transmitters. However, until better methods are available, management of pain should be individualized in a multidisciplinary setting to ensure optimal care.

Oral Prolonged-Release Oxycodone/Naloxone for Managing Pain and Opioid-Induced Constipation: A Review of the Evidence.

BACKGROUND: Opioids provide effective relief from moderate-to-severe pain and should be prescribed as part of a multifaceted approach to pain management when other treatments have failed. Fixed-dose oxycodone/naloxone prolonged-release tablets (OXN PR) were designed to address the opioid class effect of opioid-induced constipation (OIC) by combining the analgesic efficacy of oxycodone with the opioid receptor antagonist, naloxone, which has negligible systemic availability when administered orally. This formulation has abuse-deterrent properties, since systemic exposure to naloxone by parenteral administration would antagonize the euphoric effects of oxycodone. METHODS: A literature search was conducted to assess the evidence base for OXN PR to treat moderate-to-severe pain and its impact on bowel function, based on published clinical trials and observational studies. RESULTS: Extensive data demonstrate that OXN PR provides effective analgesia and clinically relevant improvements in bowel function in patients with OIC and moderate-to-severe cancer-related pain and noncancer pain types such as low back pain, neuropathic pain, and musculoskeletal pain. OXN PR has also been found to improve bowel function in patients with OIC refractory to multiple types of laxatives, and improve Parkinson's disease-related pain. No unanticipated safety concerns have been reported in elderly patients. CONCLUSIONS: Evidence from clinical trials and observational studies confirms that for selected patients OXN PR significantly improves moderate-to-severe chronic pain and provides relief from OIC. Treatment should be tailored to individual patients to establish the lowest effective dose. An absence of analgesic ceiling effect was seen across the clinically relevant dose range investigated (≤ 160/80 mg/day).

Development of an in vivo target-engagement biomarker for TRPA1 antagonists in humans.

AIM: To develop a non-invasive, safe and reproducible target-engagement biomarker for future TRPA1 antagonists in healthy volunteers. METHODS: Dose finding (n = 11): 3%, 10%, and 30% cinnamaldehyde (CA) and placebo (= vehicle) was topically applied on the right forearm. One-way ANOVA with post-hoc Bonferroni was used to compare between doses. Reproducibility: 10% CA doses were topically applied during one visit on both arms (n = 10) or during two visits (n = 23) separated by a washout period of 7 days. CA-induced dermal blood flow (DBF) was assessed by laser Doppler imaging (LDI) at baseline and at 10, 20, 30, 40 and 50 min post-CA. Paired t-test was used to compare between arms or visits. Concordance correlation coefficient (CCC) was calculated to assess reproducibility. Data are expressed as percent change from baseline (mean ± 95% CI). RESULTS: All three doses increased DBF compared to vehicle at all time-points, with the maximum response at 10-20 min post-CA. Dose response was found when comparing AUC0-50min of 30% CA (51 364 ± 8475%*min) with 10% CA (32 239 ± 8034%*min, P = 0.03) and 3% CA (30 226 ± 11 958%*min, P = 0.015). 10% CA was chosen as an effective and safe dose. DBF response to 10% CA was found to be reproducible between arms (AUC0-50min , CCC = 0.91) and visits (AUC0-50min , CCC = 0.83). Based on sample size calculations, this model allows a change in CA-induced DBF of 30-50% to be detected between two independent groups of maximum 10-15 subjects with 80% power. CONCLUSIONS: Evaluation of CA-induced changes in DBF offers a safe, non-invasive and reproducible target-engagement biomarker in vivo in humans to evaluate TRPA1 antagonists.

Opioid-Induced Constipation and Bowel Dysfunction: A Clinical Guideline.

OBJECTIVE: To formulate timely evidence-based guidelines for the management of opioid-induced bowel dysfunction. SETTING: Constipation is a major untoward effect of opioids. Increasing prescription of opioids has correlated to increased incidence of opioid-induced constipation. However, the inhibitory effects of opioids are not confined to the colon, but also affect higher segments of the gastrointestinal tract, leading to the coining of the term "opioid-induced bowel dysfunction." METHODS: A literature search was conducted using Medline, EMBASE, and EMBASE Classic, and the Cochrane Central Register of Controlled Trials. Predefined search terms and inclusion/exclusion criteria were used to identify and categorize relevant papers. A series of statements were formulated and justified by a comment, then labeled with the degree of agreement and their level of evidence as judged by the Strength of Recommendation Taxonomy (SORT) system. RESULTS: From a list of 10,832 potentially relevant studies, 33 citations were identified for review. Screening the reference lists of the pertinent papers identified additional publications. Current definitions, prevalence, and mechanism of opioid-induced bowel dysfunction were reviewed, and a treatment algorithm and statements regarding patient management were developed to provide guidance on clinical best practice in the management of patients with opioid-induced constipation and opioid-induced bowel dysfunction. CONCLUSIONS: In recent years, more insight has been gained in the pathophysiology of this "entity"; new treatment approaches have been developed, but guidelines on clinical best practice are still lacking. Current knowledge is insufficient regarding management of the opioid side effects on the upper gastrointestinal tract, but recommendations can be derived from what we know at present.

Pocket Pain and Neuromodulation: Negligible or Neglected?

OBJECTIVES: Pain encountered at the site of the implantable pulse generator (IPG) after invasive neuromodulation is a well-known and important complication. The reported incidence of implant site pain is variable, ranging between 0.4 and 35%. Implant site pain has never been systematically studied and no treatment guidelines are available. MATERIAL AND METHODS: We performed an observational study (study registration number mp05728) on the incidence and the determining factors of implant site pain, the subjective rating of intensity by sending questionnaires (n = 554) to our cohort of neuromodulation patients with IPGs. The number of revision surgeries and explants due to implant site pain were also analyzed. RESULTS: Total response rate was 50% (n = 278). Pain patients suffered significantly (p < 0.05) more often from IPG site pain than other patients undergoing neuromodulation therapies. Up to 64% of patients undergoing spinal cord stimulation reported IPG site discomfort or pain. Severe pocket pain was found in up to 8% of patients. No association was found between other variables (age, BMI, duration of follow-up, gender, smoking, number of pocket surgeries) and implant site pain. CONCLUSION: Pocket pain represents an important problem after invasive neuromodulation and is more prevalent in pain patients. We believe further technological improvements with miniaturized IPGs will impact the incidence of pocket pain and could even obviate the need for an IPG pocket.

Self-critical perfectionism predicts outcome in multidisciplinary treatment for chronic pain.

BACKGROUND: Self-critical perfectionistic personality features have been shown to influence the onset and perpetuation of pain symptoms. However, no study to date has investigated whether these personality features are associated with treatment response in chronic pain. METHODS: Using a naturalistic pre-post design, the present study examined the effect of self-critical perfectionism on treatment outcome in terms of self-reported pain. The study was conducted in a sample of 53 chronic non-cancer pain patients who followed Multidisciplinary Pain Education Program (MPEP), a brief, 2-week cognitive-behaviorally based psycho-educational intervention for chronic pain that was recently found to be effective in reducing pain severity. Pre- and post-treatment pain intensity levels were assessed with the visual analog scale of the McGill Pain Questionnaire-Short Form. RESULTS: Pretreatment self-critical perfectionism was significantly associated with negative treatment outcome, even after taking into account pretreatment levels of depression. CONCLUSION: Results suggest that self-critical perfectionistic personality features may negatively interfere with treatment response in patients with chronic pain. Thus, findings indicate that chronic pain patients with high levels of self-critical perfectionism may benefit less from brief interventions such as MPEP, and therefore may need more intensive and tailored treatment.

Continuum of somatosensory profiles in breast cancer survivors with and without pain, compared to healthy controls and patients with fibromyalgia.

CONTEXT: The prevalence of persistent pain among breast cancer survivors (BCS) is high, and it is unclear what distinguishes those with persistent pain from those without. Research suggests that differences in somatosensory function evaluated by quantitative sensory testing (QST) may be responsible. OBJECTIVES: This study aimed to describe somatosensory profiles in terms of hyper- and hypoesthesia in BCS with and without persistent pain using reference data from healthy controls. Second, QST parameters of BCS with and without pain were compared with those of healthy controls (i.e., a negative control group) and patients with fibromyalgia (i.e., a positive control group). METHODS: Participants (n = 128) were divided into four equal groups: healthy controls, BCS with persistent pain, BCS without persistent pain, and patients with fibromyalgia. Nine QST parameters were evaluated at the trunk and at a remote location. Somatosensory profiles were determined by Z-score transformation of QST data using normative data from healthy controls. RESULTS: At the trunk, compared to healthy controls, BCS with persistent pain exhibited sensory aberrations across five out of seven QST parameters: pressure pain threshold, mechanical detection, and thermal thresholds. Pain-free BCS showed similar sensory aberrations across the four QST parameters compared to healthy controls: mechanical detection and thermal thresholds. Temporal summation and conditioned pain modulation were not significantly different between groups. CONCLUSION: BCS with persistent pain exert aberrations in peripheral processing of nociceptive signals, heightened facilitation of nociceptive signals, and higher psychosocial burden when compared to pain-free BCS, healthy controls, and patients with fibromyalgia. SIGNIFICANCE: This study investigates the somatosensory function of breast cancer survivors with and without persistent pain using quantitative sensory testing and two control group (i.e., patients with fibromyalgia and healthy controls). Our results indicate somatosensory aberrations within the peripheral, but not central pathways in breast cancer survivors with persistent pain. Our findings contribute to a better understanding of the somatosensory mechanisms underlying persistent pain, which may inform future interventions to prevent the development of persistent pain, and improve treatment modalities.