Introduction
The field of palliative care is establishing a role earlier in patients’ life-limiting illnesses. Key studies in oncology have shown benefit in symptom management and quality of life to substantiate this (Zhuang et al. Reference Zhuang, Ma and Wang2018). The move to introduce palliative care early in the nonmalignant chronic disease setting is also growing, broadening the range of patient diagnoses and disease trajectories managed by palliative care (Tassinari et al. Reference Tassinari, Drudi and Monterubbianesi2016). As a consequence of early referral, some patients will be seen by palliative care clinicians many months to years prior to death. This shift brings certain challenges not previously faced by clinicians who historically saw only patients with cancer and/or very short prognoses. One such challenge is the management of patients with chronic pain (Jones and Kamal Reference Jones and Kamal2021). This can include patients with chronic nonmalignant pain or mixed pain diagnoses which include cancer-related pain and cancer treatment–related pain.
Pain management is a core component of palliative care. Fear of increasing pain and the desire to be pain free are common concerns stated by patients referred to palliative care services (Bhatnagar and Gupta Reference Bhatnagar and Gupta2016). Effective pain management remains a focus for the clinician with regard to clinical practice, research, and service delivery/benchmarking (Daveson et al. Reference Daveson, Allingham and Clapham2021). However, pain management in the palliative care setting has stemmed historically from managing cancer pain, which is routinely treated differently to nonmalignant pain. In people with cancer, pain is generally managed through the early introduction of opioids and a focus on absolute pain reduction, as outlined in the European Society of Medical Oncology guidelines (Fallon et al. Reference Fallon, Giusti and Aielli2018). Achieving adequate pain control using pharmacological treatment approaches is considered standard practice for oncology patients (Kurita and Sjogren Reference Kurita and Sjogren2021).
Chronic pain is defined as pain existing for more than 3–6 months (Scholz et al. Reference Scholz, Finnerup and Attal2019). This is because it is beyond the time expected for an injury to heal and acute pain to resolve. Chronic pain can be due to ongoing tissue damage, as in the case of advanced cancer, or it can occur in the absence of demonstrable tissue damage, due to abnormal processing of signals in the somatosensory system in the spinal cord and brain. Chronic pain is associated with lower quality of life, significant psychological distress, and increased medical co-morbidities (Currow et al. Reference Currow, Clark and Kamal2015). The encounter with pain is a subjective experience of the sensory neural input modulated by a person’s genetic predisposition, prior learning, and the current physiological, mood, and environmental state (Turk and Gatchel Reference Turk and Gatchel2018). Furthermore, taking analgesics does not adequately address the distress and disability experienced by patients with chronic pain when there is no serious demonstrable tissue damage.
Chronic nonmalignant pain is a significant problem worldwide, documented to affect around 20% of the general population in the United States and almost half the adult population in the United Kingdom. Chronic pain is associated with worse quality of life and reduced health outcomes (Mathieson et al. Reference Mathieson, Wertheimer and Maher2020). The growing use of opioids for chronic pain has been identified internationally as an area of concern because of lack of long-term efficacy, long-term side effects, and excessive deaths and opioid diversion (McElyea et al. Reference McElyea, Sam and Hollingsworth2022). This has led to a focus on reducing opioid prescribing for chronic nonmalignant pain and increasing regulatory controls.
Given the prevalence of chronic nonmalignant pain across the population, it follows then that it will be experienced by at least the same proportion of patients referred to palliative care services, and possibly greater. Coexisting chronic nonmalignant pain can complicate management of new pains related to a life-limiting condition due to sensitization of the somatosensory system. Further, while person-centered care underpins both chronic pain management and palliative care, the management approach differs. Multidisciplinary pain clinics focus on the biopsychosocial approach in their treatment of chronic pain. This approach addresses any persistent tissue damage as well as the range of social and psychological contributors to the person’s experience of pain. Inherent in such treatment is prioritizing optimal function; acknowledging pain is likely to persist rather than expecting resolution; and thus, promoting a philosophy of learning to live well despite the presence of pain. Elements of this approach include pain education and cognitive behavioral therapy to counteract any unhelpful thoughts and behaviors (Turk and Gatchel Reference Turk and Gatchel2018). In contrast, palliative care begins with the understanding of a patient’s life-limiting illness and the notion of relief of suffering. This latter approach has an inherent urgency and emotionality, which drives most clinicians to use pharmacological and supportive measures to rapidly relieve the pain. Engaging the patient in cognitive and psychological strategies to manage persistent pain is often secondary in palliative care.
The pain management of someone with a very short prognosis is likely to be similar, whether the pain is due to their cancer or chronic back pain, with the focus on analgesics. The clinical difficulty lies with those who have a longer prognosis and chronic nonmalignant pain as the main concern. It is these patients who may potentially benefit from non-pharmacological treatment modalities that are more patient-centered and responsive to psychological and social needs. The increasing concern regarding safety and management of opioid harm in the palliative care context was the topic of a recent Delphi study (Lau et al. Reference Lau, Mazzotta and Whelan2022). Currently, there is limited evidence and guidance for clinicians on the assessment and management of patients with chronic pain who are receiving palliative care. Research into this area is needed (Hui et al. Reference Hui, Abdelghani and Chen2020).
Objective
The objective of this study was to review the evidence for the prevalence and clinical management of patients with chronic nonmalignant pain referred to palliative care services.
Methods
Design
A systematic review was registered on PROSPERO (CRD42021205432) and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (Liberati et al. Reference Liberati, Altman and Tetzlaff2009).
Search strategy
Six databases including PubMed and Ovid MEDLINE, Elsevier Scopus, PsychINFO, the Cochrane Library, and CINAHL were searched on 25 August 2020 and repeated on 11 July 2022, using the following MeSH search terms: “chronic pain” OR “chronic nonmalignant pain” OR “chronic non-malignant pain” OR “chronic non cancer pain” OR “chronic non-cancer pain” OR “somatoform disorders” AND “palliative care” OR “terminal care” OR “palliative medicine” OR “hospice care” OR “end of life care” OR “terminally ill” AND “analgesics” OR “analgesia” OR “cognitive behavioural therapy” OR “physical therapy modalities” OR “exercise therapy” OR “pain management” OR “mind body therapies” AND “prevalence” OR “treatment outcomes” OR “quality of life.” No limitation to the search was made for publication date or study type. An example of the search strategy is shown in Supplement 1.
Eligibility criteria
As per our objective, studies were included if they involved persons with chronic nonmalignant pain referred to palliative care services. In this review, palliative care services were those providing specialist palliative care to people with advanced cancer or other progressive life-threatening medical conditions, and chronic nonmalignant pain was defined by clinician review establishing likely nonmalignant causation. The scope of the search was limited to patients referred to palliative care services so that the literature was relevant to that specific clinical setting. Other inclusion criteria were (1) adult participants (i.e., aged 18 years or older); (2) prevalence studies or any form of management studies (pharmacological and non-pharmacological) or guidelines implementation; (3) sample size N ≥ 50 to avoid qualitative-only or underpowered studies; and (4) published in English. Articles were excluded if they reported studies of cancer pain only or were commentaries or case reports.
Study selection
Studies were independently screened in Covidence by 2 reviewers using the above inclusion and exclusion criteria. Initial screening was of title and abstract and then full texts were sourced for articles potentially meeting the eligibility criteria. Discrepancies regarding study inclusion were resolved by discussion.
Data extraction
Data extracted included study characteristics (place, year of publication, and setting); participant characteristics (gender, number, age, diagnoses, and cancer status if present); key diagnostic group’s eligibility criteria, prevalence measures, and outcomes (chronic nonmalignant pain prevalence and treatment type/effectiveness); opioid usage, including doses expressed as total daily dose (TDD) in milligram oral morphine equivalents (OME), as documented by respective studies. Data were extracted into an Excel spreadsheet and reviewed by a second reviewer.
Risk of bias assessment
Risk of bias assessment was independently performed by 2 reviewers using the National Institute of Health’s Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, comprising 14-questions plus an overall judgment as poor, fair, or good (National Heart 2021).
Data synthesis
Study data are summarized in a table, and prevalence and effectiveness measures and results were narratively synthesized, with mean/median summary estimates and associated ranges of numerical data provided. Meta-analyses were not possible given the heterogeneity of the included studies.
Results
The combined database searches returned 450 references, reduced to 417 after removing duplicates. Full text review of 7 articles identified 5 eligible articles, published between 2014 and 2020, that were included in this review (Figure 1).
PRISMA flowchart.
Of the 5 included studies, 4 were performed in the United States (Childers et al. Reference Childers, King and Arnold2015; Hui et al. Reference Hui, Abdelghani and Chen2020; Jennings et al. Reference Jennings, Cassel and Fletcher2014; Molony et al. Reference Molony, Westfall and Perry2014) and 1 in Hong Kong (Chan et al. Reference Chan, Yap and Yip2018). All included studies were observational: 2 were cohort (Chan et al. Reference Chan, Yap and Yip2018; Jennings et al. Reference Jennings, Cassel and Fletcher2014) and 3 were cross-sectional studies (Childers et al. Reference Childers, King and Arnold2015; Hui et al. Reference Hui, Abdelghani and Chen2020; Molony et al. Reference Molony, Westfall and Perry2014). Two studies measured outcomes over time (initial visit and first follow-up) (Chan et al. Reference Chan, Yap and Yip2018; Jennings et al. Reference Jennings, Cassel and Fletcher2014). Three were supportive care clinics situated in cancer centers (Childers et al. Reference Childers, King and Arnold2015; Hui et al. Reference Hui, Abdelghani and Chen2020; Jennings et al. Reference Jennings, Cassel and Fletcher2014); 1 was a renal supportive care clinic (Chan et al. Reference Chan, Yap and Yip2018) and the other was a human immunodeficiency virus (HIV)/pain supportive care clinic (Molony et al. Reference Molony, Westfall and Perry2014). Sample sizes ranged from 137 to 323, with a total of 1056 patients.
Each study measured patients’ multiple pain types or diagnoses differently. One study (Chan et al. Reference Chan, Yap and Yip2018) limited analysis to patient’s “worst” pain only. Two studies documented up to 3 pain diagnoses per patient (Childers et al. Reference Childers, King and Arnold2015; Hui et al. Reference Hui, Abdelghani and Chen2020). One study documented only back pain (Molony et al. Reference Molony, Westfall and Perry2014), and one study did not comment on different pain diagnoses (Jennings et al. Reference Jennings, Cassel and Fletcher2014). Pain assessment used the Edmonton Symptom Assessment Scale (Chan et al. Reference Chan, Yap and Yip2018; Hui et al. Reference Hui, Abdelghani and Chen2020) in 2 studies and a Visual Analogue Scale/Numerical Rating Scales (Chan et al. Reference Chan, Yap and Yip2018; Jennings et al. Reference Jennings, Cassel and Fletcher2014) in 2 studies. One study did not use a pain measure, rather a clinician’s assessment of aetiology (Molony et al. Reference Molony, Westfall and Perry2014).
Prevalence of chronic nonmalignant pain
Prevalence of chronic nonmalignant pain ranged from 14% to 34% across the studies (Table 1). A study of 200 patients in a supportive care clinic at a US comprehensive cancer center recorded up to 3 pain diagnoses per patient and found that 67 had chronic nonmalignant pain (34%) (Hui et al. Reference Hui, Abdelghani and Chen2020). There was a strong association between the number of pain diagnoses and the likelihood of chronic nonmalignant pain, the odds ratio of associated chronic nonmalignant pain if a patient has 3 diagnoses versus one being 75 (95% confidence interval 10.8–520.7, p = 0.001). In addition, there was a significant overlap in patients presenting with chronic nonmalignant pain, cancer-related pain, and cancer treatment–related pain: of 67 patients with chronic nonmalignant pain, 36 (54%) also had cancer-related pain or cancer treatment–related pain (Hui et al. Reference Hui, Abdelghani and Chen2020). Another US study of 323 patients of a supportive care clinic in an academic medical center reported that 87 (27%) had chronic nonmalignant pain and another 90 (28%) had no evidence of cancer disease (Childers et al. Reference Childers, King and Arnold2015). A study in a renal supportive clinic reported overall pain prevalence of 44%; of these patients, 49% had chronic pain (Chan et al. Reference Chan, Yap and Yip2018). In a study in an HIV supportive care clinic which exclusively examined back pain, 55% of patients had back pain and 14% had chronic back pain (Molony et al. Reference Molony, Westfall and Perry2014).
Study characteristics
Overall risk of bias assessment: poor (0), fair (+), good (++)
a Multiple pain types per person, so % > 100 (361 pain diagnoses in 200 pts)
b Center for AIDS Research Network of Integrated Clinical Systems prospective cohort study (includes >90% clinic pts)
AC = active cancer, BPI = brief pain inventory, CAGE-AID = cut down–Annoyed-Guilt–Eye-opener–Adapted to Include Drugs, CCI = Charlton Comorbidity Index, CKD = chronic kidney disease, CNMP = chronic nonmalignant pain, ESAS = Edmonton Symptom Assessment Scale, HIV = human immune deficiency, K/DOQI = Kidney Disease Outcome Quality Initiative, MEDD = Morphine Equivalent Daily Dose, MRI = magnetic resonance imaging, NED = no evident disease, NLLI = no life-limiting illness, NRS = numerical rating scale, PHQ-9 = Patient Health Questionnaire-9, PHQ-9A = Patient Health Questionnaire-9Anxiety, PROM = Patient Reported Outcome Measures, pts = patients, SOAPP-14 = Screener and Opioid Assessment for Patients with Pain-14, SOAPP-SF Screener and Opioid Assessment for Patients with Pain v 1.0 – short form, SCC = supportive care clinic, VAS = Visual Analogue Scale, y = years
Treatment of chronic nonmalignant pain
Types of treatment
Three studies reported opioid use, with all finding lower usage in chronic nonmalignant pain compared to cancer pain (Chan et al. Reference Chan, Yap and Yip2018; Hui et al. Reference Hui, Abdelghani and Chen2020; Jennings et al. Reference Jennings, Cassel and Fletcher2014). In the comprehensive cancer center, for the 361 pain diagnoses, patients with chronic nonmalignant pain were significantly less likely to be on opioids (30/94 [32%]) compared to patients with cancer treatment–related pain (28/60 [47%]) and cancer-related pain (120/182 [66%]; p < 0.0001) (Hui et al. Reference Hui, Abdelghani and Chen2020). In the academic medical center’s cancer supportive care clinic, patients were already on high-dose opioids (average TDD > 300 mg OME) at initial assessment but trended toward lower doses in those with no evidence of cancer disease (mean 208.7 mg and SD 205.2 mg) and no life-limiting illness (mean 258.9 mg and SD 613.9 mg) compared with cancer pain (mean 393.1 mg and SD 463.1 mg, p = 0.18) (Jennings et al. Reference Jennings, Cassel and Fletcher2014). The renal supportive care clinic study reported low rates of strong opioid prescription (3%), with simple analgesics used in 92% of patients and weak opioids in 29%. (Chan et al. Reference Chan, Yap and Yip2018)
Response to opioids
Only 2 studies evaluated treatment outcomes, each at or around 1 month (Chan et al. Reference Chan, Yap and Yip2018; Jennings et al. Reference Jennings, Cassel and Fletcher2014). Both studies included adjuvant analgesics as well as opioids. Neither study documented any non-pharmacological treatments, nor described the overall components of the supportive care provided. The first study was that set in the renal supportive care clinic (Chan et al. Reference Chan, Yap and Yip2018). This study used the Edmonton Symptom Assessment Scale score pre and post review to measure treatment response to weak or strong opioids according to the World Health Organization ladder in the subset with moderate–severe pain, although they did not distinguish between acute and chronic pain. The overall change in mean scores was reduced from baseline 4.5 (SD 1.9) to 2.3 (SD 2.2) (p < 0.05). For those with moderate to severe pain (>4), the treatment response was greater: baseline 5.8 (SD 1.9) to 2.9 (2.5) (p = 0.007) (Chan et al. Reference Chan, Yap and Yip2018). The second study measuring treatment outcome was in an academic medical center’s cancer supportive care clinic (Jennings et al. Reference Jennings, Cassel and Fletcher2014). Opioid doses were titrated, and 6–20% of patients showed no statistical difference in opioid dosing at initial or first review (p = 0.28). The documented treatment included medication management involving opioid and non-opiate analgesia. This study defined treatment responders as those with a 2-point reduction in the Numerical Rating Scale or at least 30% reduction from baseline. An overall treatment response of 44% was reported; the greatest response was in patients with active cancer (57.4%) compared to those with no life-limiting illness (41%) and no evident disease (20%) (p = 0.0091) (Jennings et al. Reference Jennings, Cassel and Fletcher2014).
Measures of alcohol or opioid misuse
Two studies measured alcohol dependence and risk of opioid misuse (Childers et al. Reference Childers, King and Arnold2015; Hui et al. Reference Hui, Abdelghani and Chen2020). Alcohol dependence was measured by versions of the Cut down–Annoyed–Guilt–Eye-opener (CAGE) tool in 2 studies (Childers et al. Reference Childers, King and Arnold2015; Hui et al. Reference Hui, Abdelghani and Chen2020). Risk of opioid misuse was assessed using 2 versions of the Screener and Opioid Assessment for Patients with Pain (SOAPP) tool in 2 studies (Childers et al. Reference Childers, King and Arnold2015; Hui et al. Reference Hui, Abdelghani and Chen2020). One study reported no difference in alcohol dependence or risk of misuse for those with chronic nonmalignant pain and the overall population (Hui et al. Reference Hui, Abdelghani and Chen2020). The other study found that 46% of all new patients had an elevated risk of opioid misuse according to SOAPP; however, the CAGE assessment indicated low rates of alcohol dependence (Childers et al. Reference Childers, King and Arnold2015). The risk of opioid misuse in the latter study was associated with younger age (50 vs. 61 y; p = 0.007) (Childers et al. Reference Childers, King and Arnold2015).
Risk of bias assessment
Regarding risk of bias, all 5 studies were assessed as “fair” on the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies (National Heart, Lung and Blood Institute 2021) (Figure 2 and Table 1). All studies were at high risk of detection bias due to use of a single tool for pain assessment. Three studies recorded only one type of pain diagnosis per patient, and the effect of this potential confounder was not addressed in those studies. Four of the 5 studies were at a single site, where referral and patient characteristics were unique, limiting generalizability. Four out of 5 studies did not report sample size calculations or precision estimates in study design. The overall risk of bias is presented in Figure 2.
Risk of bias assessment.
Discussion
This systematic review of the prevalence and management of chronic nonmalignant pain in patients receiving palliative care revealed few relevant studies. The prevalence of chronic nonmalignant pain was found to be between 14% and 34% across a range of supportive care clinic populations. Lower rates of opioid analgesics were reported for patients with chronic nonmalignant pain. However, opioid use was common in these patients; the range of use was 39–58%, depending on the coexistence of cancer-related or cancer treatment–related pain. The risk of opioid misuse was estimated at 46% of patients in one study (Childers et al. Reference Childers, King and Arnold2015).
This review highlights the difficulty in isolating chronic nonmalignant pain from a patient’s overall experience of pain. Up to half the patients with chronic nonmalignant pain had comorbid cancer-related or cancer treatment–related pain. Differences in the number of pain diagnoses studied raised the question of missed chronic nonmalignant pain diagnoses, especially when malignant pain was the focus of the study. While one study documented up to 3 pain diagnoses or types, the other studies did not assess multiple pain types experienced by patients. The clinical picture and subsequent management decisions are challenging, given the mixed nature of pain and the fact that patients can experience multiple pain types or diagnoses currently.
While one might question the attention on pain diagnoses or causation in the palliative setting, the lessons from chronic pain research are important to heed. The benefit of opioid prescription and dose escalation in the chronic pain setting is limited; the updated Centers for Disease Control and Prevention (CDC) guideline recommends dose reduction and avoidance of opioids wherever possible (Dowell et al. Reference Dowell, Ragan and Jones2022). Opioid prescription can be associated with misuse and can have significant side effects, which have historically been minimized in palliative care settings where cancer pain predominated and prognosis was short.
Patients have long been concerned with analgesic side effects and sought more use of non-pharmacological approaches to pain management (Jennings et al. Reference Jennings, Cassel and Fletcher2014). In the oncology setting, goals of care toward the end of life have focused on sustaining the quality of life and reducing suffering. The immediate reduction of pain, with analgesics and other treatment modalities, has been a target for most clinicians. Even here, the need for careful education, enhanced communication, personalized care, and the use of non-pharmacological approaches have been called for (Azizoddin et al. Reference Azizoddin, Schreiber and Beck2021). When we look to a future where palliative medicine contributes to more non-oncological care and earlier involvement with patients long before the terminal phase, the management of patients with chronic nonmalignant pain requires whole-person care alongside relief of their distress and morbidity.
This review shows the limited research that has been done into this evolving area of palliative care. The management of patients with both chronic nonmalignant pain and life-limiting illness is complex and is currently left out of both chronic pain and palliative care guidelines, respectively. The prevalence of chronic nonmalignant pain in these studies mirrors that of the general population, where chronic pain estimates are increasing. Future research into the intersection of chronic nonmalignant pain and palliative care is timely and would inform an evidence-based approach to best clinical care for these patients.
Limitations
The studies included in this review had small, cross-sectional samples from single outpatient sites and nearly all were conducted in the US. Pain assessment was generally limited to a single numerical screening tool. There was no attention to psychological components of pain, associations of which have been shown to be significant in the chronic pain literature. The modality of diagnosis of nonmalignant pain was only described in 2 studies. The medication history was documented in only 3 studies, and of them opioid and non-opioid medications were reported in only 2. The result is a heterogeneous picture which restricts generalization, and the study quality was assessed as fair. Some institutions lack a comprehensive chronic pain service, causing pain referrals to be made to palliative care programs, which are not necessarily staffed to respond to chronic pain. In addition, we included studies in renal supportive and HIV/pain supportive clinics, which are clearly specialized and increased the heterogeneity of the studies reviewed.
Funding
This review was undertaken with no external funding.
Conflicts of interest
The authors report no conflict of interest.
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