The Relationship between Cognitive and Emotional Factors and Healthcare and Medication Use in People Experiencing Pain: A Systematic Review

Pain conditions are among the leading causes of global disability, impacting on global healthcare utilization (HCU). Health seeking behavior might be influenced by cognitive and emotional factors (CEF), which can be tackled by specific therapies. The purpose of this study was to systematically review the evidence concerning associations between CEF and HCU in people experiencing pain. Three databases were consulted: PubMed, Web of Science and EconLit. Risk of bias was assessed using the Downs and Black Checklist (modified). A total of 90 publications (total sample n = 59,719) was included after double-blind screening. In people experiencing pain, positive associations between general anxiety symptoms, depressive symptoms and catastrophizing and pain medication use were found. Additionally, there appears to be a relationship between general anxiety and depressive symptoms and opioid use. Symptom-related anxiety and psychological distress were found to be positively related with consulting behavior. Last, a positive association between use of complementary and alternative medicine and level of perceived symptom control was confirmed in people with pain. For other relationships no evidence or inconsistent findings were found, or they were insufficiently studied to draw firm conclusions, indicating that more research on this topic is needed.

12. Were the staff, places, and facilities where the patients were treated, representative of the treatment the majority of patients receive?
For the question to be answered "Yes" the study should demonstrate that the intervention was representative of that in use in the source population. The question should be answered "No" if, for example, the intervention was undertaken in a specialist center unrepresentative of the hospitals most of the source population would attend. This question should be answered "Not applicable (NA)" for studies without intervention (i.e., cross-sectional, observational cohort and case-control studies).

Yes = 1
No = 0 Unable to determine = 0 NA Internal validity -bias 13. Was an attempt made to blind study subjects to the intervention they have received?
For studies where the patients would have no way of knowing which intervention they received, this should be answered "Yes". For studies where blinding of patients is impossible due to the nature of the intervention/control intervention, the question should be answered "Not applicable (NA)". If the study did not comprise an intervention (i.e., cross-sectional, observational cohort and case-control studies) or there was no control group (i.e., single group interventional cohort studies), this question should be answered "Not applicable (NA)". If the study did not comprise an intervention (i.e., cross-sectional, observational cohort and case-control studies) or there was no control group (i.e., single group interventional cohort studies), this question should be answered "Not applicable (NA)".

Yes = 1 No = 0
Unable to determine = 0 NA 15. If any of the results of the study were based on "data dredging", was this made clear?
Any analyses that had not been planned at the outset of the study should be clearly indicated. If no retrospective unplanned subgroup analyses were reported, then answer "Yes".

Yes = 1
No = 0 Unable to determine = 0 16. In trials and cohort studies, do the analyses adjust for different lengths of follow-up of patients, or in case-control studies, is the time period between the intervention and outcome the same for cases and controls ?
If follow-up was the same for all study patients the answer should be "Yes". If different lengths of follow-up were adjusted for by, for example, survival analysis the answer should be "Yes". Studies where differences in follow-up were ignored should be answered "No". Also in studies with only one group of participants, follow-up should be more or less the same. For studies with only one moment of assessment (no follow-up) (i.e., cross-sectional and some case-control studies) this question should be answered "Not applicable (NA)".

Yes = 1 No = 0
Unable to determine = 0 NA 17. Were the statistical tests used to assess the main outcomes appropriate?
The statistical techniques used must be appropriate for the data (distribution). For example nonparametric methods should be used for small sample sizes. Where little statistical analysis has been undertaken but where there is no evidence of bias, the question should be answered "Yes". If the distribution of the data (normal or not) is not described it must be assumed that the estimates used were appropriate and the question should be answered "Yes". If only very limited information is provided about the planned statistical analyses, the question should be answered "Unable to determine". Where there was non-compliance with the allocated treatment or where there was contamination of one group, the question should be answered "No". For studies where the effect of any misclassification was likely to bias any association to the null, the question should be answered "Yes". This question should be answered "Not applicable (NA)" if the study did not include an intervention (i.e., crosssectional, observational cohort and case-control studies). For studies where the outcome measures are clearly described, the question should be answered "Yes". For studies which refer to other work or that demonstrate the outcome measures are accurate, the question should be answered as "Yes". For studies using secondary databases, the answer should be "No". For studies using self-reported methods, such as healthcare diaries or retrospective questionnaires, especially designed for the present study, the answer should be "Yes". If the study is a secondary analysis from another study, but healthcare use data were registered for scientific purposes, the question should be answered "Yes". Internal validity -confounding (selection bias) 21. Were the patients in different intervention groups (trials and cohort studies) or were the cases and controls (case-control studies) recruited from the same population?
For example, patients for all comparison groups should be selected from the same hospital. The question should be answered "Unable to determine" for cohort and case-control studies where there is no information concerning the source of patients included in the study. This question should be answered "Not applicable (NA)" for cross-sectional and single group cohort studies.

Yes = 1
No = 0 Unable to determine = 0 NA 22. Were study subjects in different intervention groups (trials and cohort studies) or were the cases and controls (case-control studies) recruited over the same period of time?
For a study which does not specify the time period over which patients were recruited, the question should be answered "Unable to determine". This question should be answered "Not applicable (NA)" for cross-sectional and single group cohort studies.
Unable to determine = 0 NA 23. Were study subjects randomized to intervention groups?
Studies which state that subjects were randomized should be answered "Yes" except if the method of randomization would not ensure random allocation. For example alternate allocation would score "No" because it is predictable. This question should be answered "Not applicable (NA)" for studies without intervention (i.e., cross-sectional, observational cohort and case-control studies).

Yes = 1
No = 0 Unable to determine = 0 NA 24. Was the randomized intervention assignment concealed from both patients and health care staff until recruitment was complete and irrevocable?
If assignment was concealed from patients but not from staff, this question should be answered "No". This question should be answered "Not applicable (NA)" for studies without intervention (i.e., crosssectional, observational cohort and case-control studies) and for single group studies (i.e., single group interventional cohort studies).

Yes = 1
No = 0 Unable to determine = 0 NA 25. Was there adequate adjustment for confounding in the analyses from which the main findings were drawn? Demmelmaier (2010) [15] Number of consultations with 6 different healthcare providers Amount Consultations Dobkin (2006) [16] Tertiary care use vs community patients Type Tertiary care consultations Durá-Ferrandis (2017) [17] Frequency of self-medication Amount Pain medication use Elander (2003) [18] Use of comprehensive care center or another hemophilia center (yes/no)  [19] Frequency of OTC pain killer use Amount Pain medication use Frequency of prescription pain medication use Amount Pain medication use Engel (1996) [20] Number  [21] Primary vs tertiary care Type Tertiary care consultations Gebauer (2019) [22] Taking 1-50mg/day MED opioids vs none Type Opioid use Taking >50mg/day MED opioids vs none Type Opioid use Gil (2004) [23] Frequency of doctor calls on the same day, the next day or 2 days later

Amount Consultations
Frequency of hospitalizations on the same day, the next day or 2 days later

Amount Hospitalizations
Frequency of ER visits on the same day, the next day or 2 days later Amount Emergency HCU Frequency of prescription pain medication intake on the same day, the next day or 2 days later  [75] Taking opioids (yes/no) Type Opioid use Taking weak opioids (yes/no) Type Opioid use Taking strong opioids (yes/no) Type Opioid use Taking NSAID's (yes/no) Type Pain medication use Other prescription medication use (yes/no) Type Prescription pain medication use Not taking any pain medication (yes/no) Type Pain medication use Van Tilburg (2008) [76] Use of CAM services (ginger root or tea, fennel seed, senna tea, psychotherapy, homeopathic, hypnotherapy, massage therapy, biofeedback, acupuncture, yoga, aromatherapy, evening primrose oil and others) (yes/no) Type CAM use Vervoort (2019) [77] Recurrent secondary HCU (specialist consultations, diagnostic procedures, admissions to healthcare institutions, multimodal rehabilitation programs) (yes/no) Type Secondary care consultations Villani (2010) [78] Number of emergency department visits repeaters/nonrepeaters Amount Emergency HCU Vina (2019) [79] Oral opioid use vs oral non-opioid analgesic use Type Opioid use Oral opioid use vs no oral analgesic use Type Opioid use Oral non-opioid analgesic use vs no oral analgesics use Type Pain medication use Von Korff (1991) [80] Healthcare contact with a doctor, PT, dentist, chiropractor or other professional for a pain problem (yes/no)  [83] Use of one of the following services for pain condition: PT, psychology, massage therapy and other medical services (yes/no for each; summed to a 0-4 score for use of different healthcare services)

Amount Consultations
Use of any of the following medications for pain condition: OTC NSAID's, opioids, prescription anti-inflammatory drugs or psychotropic drugs (yes/no for each; summed to a 0-4 score for use of different pain medications) Amount Pain medication use Wijnhoven (2007) [84] Contacts with GP, medical specialist or physiotherapist (yes/no) Type Consultations Use of medicines for musculoskeletal pain (yes/no) Type Pain medication use Williams (2006) [85] Having a doctor's visit for abdominal symptoms (yes/no) Type Consultations Williams (2018) [86] Frequency of ER visits Amount Emergency use Frequency of day hospital visits Amount Consultations Frequency of hospitalizations Amount Hospitalizations Wong (2019) [87] Amount of postoperative opioid use Amount Pain medication use Woodhouse (2016) [88] -conventional care (physicians, PT, chiropractors and psychologists; both conventional and alternative care; prescribed medications; sick leave) -alternative care (osteopaths, naprapaths, homeopaths, acupuncturists or other alternative healthcare providers and treatments) Intake of prophylactic medication for headache for ≥3m Amount Pain medication use Zondervan (2001) [90] Consultation with GP or hospital doctor for any pelvic pain (yes/no) -Received a diagnosis or underwent an investigation for any pelvic pain in the past (yes/no) Categorized into: -Recent consulters (sought care in the past 12 m) -Past consulters (did not consult in the past 12 m but received a diagnosis or underwent an investigation in the past) -Non-consulters (never had a consultation, diagnosis or investigation for pelvic pain) Amount Consultations 1 Two main categories of HCU outcomes: (1) amount or frequency of HCU and (2) type of HCU 2 Subcategories for "Amount of HCU": pain medication use, consultations, emergency HCU, hospitalizations, complementary and alternative medicine (CAM) use, invasive procedures and HCU in general (in case the study did not make any further specifications). Subcategories for "Type of HCU": pain medication (in case no further specification was made), OTC pain medication, prescription pain medication (excluding opioids), opioids, consultations (in case no further specification was made), primary care consultations, secondary care consultations, tertiary care consultations, emergency HCU, invasive procedures, hospital admissions and CAM use. Outcome measures that combined consultations with hospitalizations were categorized as "HCU in general", those combining consultations, CAM consultations and/or ER visits were categorized as "consultations".   General anxiety symptoms x pain medication use Daltroy (1998) 5 [13]  vitality and pain) (all above NSomitted from final model), sex (S), SF-36 scores (physical function, health perception and mental health) (S), marital status (S), diagnosis (S), death of a sibling (S) and reported sexual abuse (S).

Number of GP consultations
Regression investigating the influence of HADS-A score on the number of GP consultations while also accounting for education, access to confidant, pain score, recent social stress, exposure to death of a father or mother during childhood, reported childhood adversity (sexual abuse, antipathy from mother, neglect, physical abuse or psychological abuse), depressive symptoms, symptomrelated anxiety symptoms, negative consequences beliefs, perceived symptom control, SF-36 scores (role limitations physical and mental, social function, energy and vitality, physical function, health perception and mental health) (all above NS -omitted from final model), sex (S), SF-36 pain score (S), marital status (S), illness perception timeline score (S), diagnosis (S), death of a sibling (S) and reported antipathy from father (S).

Number of GP consultations
Regression investigating the influence of HADS-D score on the number of GP consultations while also accounting for education, access to confidant, pain score, recent social stress, exposure to death of a father or mother during childhood, reported childhood adversity (sexual abuse, antipathy from mother, neglect, physical abuse M NS (omitted from final model) or psychological abuse), general and symptom-related anxiety symptoms, negative consequences beliefs, perceived symptom control, SF-36 scores (role limitations physical and mental, social function, energy and vitality, physical function, health perception and mental health) (all above NS -omitted from final model), sex (S), SF-36 pain score (S), marital status (S), illness perception timeline score (S), diagnosis (S), death of a sibling (S) and reported antipathy from father (S).

Number of consultations w/ other providers than GP
Regression investigating the influence of HADS-D score on the number of consultations w/ other providers than GP while also accounting for marital status, diagnosis, education, access to confidant, recent social stress, exposure to death of a sibling, father or mother during childhood, reported childhood adversity (sexual abuse, antipathy from father or mother, neglect, physical abuse or psychological abuse), general and symptom-related anxiety symptoms, negative illness perceptions (consequences and timeline), perceived symptom control, SF-36 scores (pain score, role limitations physical and mental, social function, energy and vitality, physical function, health perception and mental health) (all above NS -omitted from final model), sex (S), SF-36   scores (physical function, health perception and mental health) (S), marital status (S), diagnosis (S), death of a sibling (S) and reported sexual abuse (S).

Number of GP consultations
Regression investigating the influence of negative consequences score on the number of GP consultations while also accounting for education, access to confidant, pain score, recent social stress, exposure to death of a father or mother during childhood, reported childhood adversity (sexual abuse, antipathy from mother, neglect, physical abuse or psychological abuse), depressive symptoms, general and symptom-related anxiety symptoms, perceived symptom control, SF-36 scores (role limitations physical and mental, social function, energy and vitality, physical function, mental health and health perception) (all above NS -omitted from final model), sex (S), SF-36 pain score (S), marital status (S), illness perception timeline score (S), diagnosis (S), death of a sibling (S) and reported antipathy from father (S  Regression investigating the influence of the timeline score on the number of consultations w/ other providers than GP while also accounting for marital status, diagnosis, education, access to confidant, recent social stress, exposure to death of a sibling, father or mother during childhood, reported childhood adversity (sexual abuse, antipathy from father or mother, neglect, physical abuse or psychological abuse), depressive symptoms, general and symptom-related anxiety symptoms, negative illness perceptions (consequences), perceived symptom control, SF-36 scores (pain score, role limitations physical and mental, social function, energy and vitality, physical function and health perception) (all above NS -omitted from final model), sex (S), SF-36 (health perception, mental health and physical function) (S) and pain score (S).   Number of consultations w/ healthcare providers Regression investigating the influence of level of perceived symptom control on the number of consultations while also accounting for education, access to confidant, pain score, recent social stress, exposure to death of a father or mother during childhood, reported childhood adversity (antipathy from father or mother, neglect, physical abuse or psychological abuse), depressive symptoms, general and symptom-related anxiety symptoms, negative illness perceptions (consequences and timeline), SF-36 scores (role limitations physical and mental, social function, energy and vitality and pain) (all above NSomitted from final model), sex (S), SF-36 scores (physical function, health perception and mental health) (S), marital status (S), diagnosis (S), death of a sibling (S) and reported sexual abuse (S).    [22] Chronic low back pain anxiety symptoms yes/no symptoms (reference: no symptoms) on the likelihood of using 1-50mg/d MED (reference: no opioid use) while also accounting for moment of assessment (NS), collecting disability (    Regression investigating the influence of IPQ-R consequences score on the likelihood of using pain medication (reference: no use) while also accounting for sex (NS -fixed factor), age (NSfixed factor), diagnosis (S -fixed factor), IPQ-R subscales (timeline cyclical (S), identity (S), emotional representations (S), treatment control (S), and illness coherence (S)) and frustration (S). Regression investigating the influence of IPQ-R consequences score on the likelihood of having a GP consultation (reference: no consultation) while also accounting for sex (NS -fixed factor), age (S -fixed factor), diagnosis (NS -fixed factor) and IPQ-R subscales (timeline acute/chronic, emotional representations, identity and treatment control; all S). Multivariate Regression investigating the influence of IPQ-R timeline cyclical score on the likelihood of using pain medication (reference: no use) while also accounting for sex (NS -fixed factor), age (NS -fixed factor), diagnosis (S -fixed factor), IPQ-R subscales (consequences (S), identity (S), emotional representations (S), treatment control (S), and illness coherence (S)) and frustration (S). Regression investigating the influence of IPQ-R timeline acute/chronic on (reference: low score) on the likelihood of using pain medication (reference: no use) while also accounting for IPQ-R items (personal control and psychological attributions; both NS -omitted from final model), sex (NS -fixed factor), age (NS -fixed factor) and diagnosis (S -fixed factor), remaining IPQ-R items (timeline cyclical, consequences, treatment control, emotional representations, illness coherence and identity; all S) and frustration score (S). Regression investigating the influence of IPQ-R timeline cyclical score on the likelihood of pain medication use (reference: no use) while also accounting for IPQ-R items (personal control, illness coherence and psychological attributions), frustration (all above: NSomitted from final model), sex (NS -fixed factor), age (S -fixed factor), diagnosis (NS -fixed factor) and remaining IPQ-R items (timeline acute/chronic, consequences, treatment control, emotional representations and identity; all S). Regression investigating the influence of having a high IPQ-R timeline acute/chronic score (reference: low score) on the likelihood of having a GP consultation (reference: no consultation) while also accounting for sex (NS -fixed factor), age (S -fixed factor), diagnosis (NS -fixed factor) and IPQ-R subscales (emotional representations, identity, consequences and treatment control; all S). while also accounting for sex (NS -fixed factor), age (NS -fixed factor), diagnosis (S -fixed factor), IPQ-R subscales (timeline cyclical (S), identity (S), consequences (S), treatment control (S), and illness coherence (S)) and frustration (S). Psychological distress x prescription pain medication use Navabi (2018) 5