Abstract
Background:
Chronic pain negatively impacts sleep; it is unclear whether pain relief from acupuncture contributes to sleep quality improvements in cancer survivors. This study aimed to evaluate the effect of acupuncture versus usual care on sleep quality among cancer survivors with comorbid sleep disturbance and chronic musculoskeletal pain.
Methods:
We analyzed sleep outcome data from the PEACE randomized clinical trial. We compared electroacupuncture or auricular acupuncture versus usual care for sleep quality improvement over ten weeks of treatment among cancer survivors with clinically significant sleep disturbance and chronic musculoskeletal pain at baseline. We measured sleep quality with the Pittsburgh Sleep Quality Index (PSQI) global score.
Results:
Among 268 participants (mean [standard deviation (SD)] age, 61.4 [12.6] years; 191 women [71.3%]; mean [SD] baseline PSQI global score, 10.3 [3.3] points), electroacupuncture resulted in greater reductions in the PSQI global score from baseline to ten weeks by 1.42 points (95% Confidence Interval [CI], 0.45–2.38; P=0.004) and auricular acupuncture by 1.59 points (95% CI, 0.62–2.55; P=0.001) compared to usual care. Improvement in sleep quality for the acupuncture groups was sustained for 24 weeks from randomization. Further, a greater proportion of patients in the electroacupuncture and auricular acupuncture groups had clinically meaningful improvement in sleep quality compared to the usual care group (41.0% and 42,9% vs. 21.4%, P=0.044).
Conclusions:
Among cancer survivors with comorbid sleep disturbance and chronic pain, electroacupuncture and auricular acupuncture produced clinically relevant and persistent improvement in sleep quality. These findings suggest acupuncture may be an evidence-based nonpharmacologic intervention to improve sleep health for cancer survivors with pain.
Keywords: cancer survivor, sleep disturbance, chronic pain, integrative care, clinical trial
Lay Summary
This study analyzed the sleep quality data from a published randomized clinical trial that evaluated the effect of electroacupuncture or auricular acupuncture versus usual care on pain relief among people who survived cancer.
This analysis included a prespecified subgroup of 268 participants with co-occurring sleep disturbance and chronic musculoskeletal pain at baseline and found that patients using acupuncture for pain relief demonstrated greater improvements in sleep quality compared with patients receiving usual care.
Sleep quality improvement by acupuncture was sustained after the treatment ended.
Precis for Use
Among cancer survivors with comorbid sleep disturbance and chronic pain, both electroacupuncture and auricular acupuncture improved sleep quality compared to usual care.
The improvement in sleep quality by acupuncture treatment was sustained to 24 weeks after randomization.
Introduction
Sleep disturbance is a common and persistent clinical complaint accounting for 60% of cancer survivors 1,2. Immediately following a diagnosis, sleep disruptions are reported in over 40% of patients with cancer, and 20% of patients still experience poor sleep quality nine years post-diagnosis 3,4. Sleep impairment in cancer is multifactorial 5, where comorbid pain plays a prominent role in precipitating, maintaining, and exacerbating sleep disturbance symptoms 6,7. The prevalence of sleep disturbances is around 60% in cancer patients with pain 8,9. Pain can disrupt sleep and contribute to impaired sleep quality 10. Previous studies offer insight into the feasibility of treating insomnia through pain relief with cognitive, behavioral therapy, or physical exercise 11–13. Therefore, effective management of pain can potentially improve sleep quality in cancer survivors 14.
Acupuncture is an effective nonpharmacologic pain intervention in cancer populations 15. Traditional medicine theories hold acupuncture unblocks meridians and balances Yin and Yang to improve pain and sleep disturbance. Basic science studies reveal that the neurobiological system/substances (i.e. opioid, monoaminergic, and orexinergic systems) contributing to acupuncture analgesia also play a critical role in maintaining sleep homeostasis 16,17. Few studies have been conducted to examine the possible benefits in sleep quality associated with pain relief from acupuncture treatment in cancer populations 18,19. Manual acupuncture led to rapid pain relief among cancer survivors with insomnia, which contributed to a decrease in insomnia 18. In breast cancer patients with aromatase inhibitor-related joint pain, electroacupuncture produced a nonsignificant improvement in sleep quality compared to usual care during the 12-week intervention and follow-up period 19.
Since pain and poor sleep often impact patients with cancer, better characterizing the effect of acupuncture on sleep quality among cancer survivors with pain can help further inform the delivery of sleep and pain interventions in oncology care. The Personalized Electroacupuncture vs Auricular Acupuncture Comparative Effectiveness (PEACE) trial demonstrated that electroacupuncture and auricular acupuncture led to clinically meaningful improvements in pain severity relative to usual care in cancer survivors with chronic musculoskeletal pain 20. Based on this study, we examined the magnitude of sleep quality changes by electroacupuncture or auricular acupuncture treatment for pain relief relative to usual care in a cohort of cancer survivors with chronic musculoskeletal pain and sleep disturbance.
METHODS
Study Design
This is a prespecified secondary analysis of clinical data from the PEACE trial (ClinicalTrials.gov Identifier NCT02979574) 20. PEACE is a randomized, three-arm, parallel clinical trial that compared the effect of electroacupuncture versus auricular acupuncture versus usual care for pain relief among cancer survivors with chronic musculoskeletal pain. Patients with chronic musculoskeletal pain were randomized 2:2:1 to receive ten acupuncture sessions (electro- or auriculo-) or usual pain care over ten weeks. Patients in the electroacupuncture and auricular acupuncture groups were evaluated with the Pittsburgh Sleep Quality Index (PSQI) for sleep quality and the Brief Pain Inventory (BPI) for pain severity at baseline, ten weeks, and 24 weeks. Because compensation in the form of acupuncture treatment was provided after 12 weeks to patients in the usual care group, they were only evaluated at baseline and ten weeks with the same outcome measurement tools. The original study was completed from March 2017 to October 2019. The Institutional Review Board at Memorial Sloan Kettering Cancer Center approved the study protocol summarized below.
Study Participants
Eligible adult participants were: 1) English-speaking; 2) had a prior cancer diagnosis and no current evidence of disease; 3) experienced musculoskeletal pain for at least three months and at least 15 days in the preceding 30 days; and 4) rated their worst pain intensity in the past week as moderate or greater (≥4 on a 0–10 numerical rating scale). Exclusion criteria included: 1) inflammatory arthritis requiring disease-modifying drugs; 2) phantom limb pain; 3) a pending pain-related Veteran Health Administration, social security, or worker’s compensation disability claim by self-report; 4) or an implanted electronically charged medical device. Patients provided informed consent before the initiation of any study procedures. The present study included only participants who have poor sleep quality as defined with at least 6 points on the PSQI global score at baseline, which is a standard cutoff in sleep medicine research for the definition of self-reported poor sleep quality 21.
Interventions:
The details of the interventions have been previously reported (Appendix) 20,22. In brief:
Electroacupuncture:
Licensed acupuncturists with more than five years of experience in oncology settings delivered ten weekly sessions of semi-standardized, protocolized treatment. Acupuncture needles (SEIRIN) were inserted at the selected points after skin disinfection and then manually manipulated to achieve De Qi, a sensation of soreness or aching. An A3922 E-STIM II device (Tens Plus Industrial Company) delivered electrical stimulation at 2Hz to four points near the pain location. All needles were withdrawn after a 30-minute retention.
Auricular acupuncture:
The same acupuncturist team also delivered the protocolized auricular acupuncture developed by the U.S. military, known as battlefield acupuncture 23. Before needle placement, the auricular skin was sterilized, and up to ten needles were administered for ten fixed auricular points based on an individual patient’s pain reactions to treatment. The total duration of each treatment session was approximately 10 to 20 minutes, depending on how many needles were administered. The needles remained in place for three to four days. Patients were instructed on how to remove the needles safely. Patients received ten treatments over ten weeks.
Usual care:
Patients received standard care for their pain as prescribed by their healthcare clinicians, including analgesic medications, physical therapy, and glucocorticoid injections. Patients were offered the option of receiving ten acupuncture treatments after week 12.
Outcomes
The PSQI is a patient-reported outcome questionnaire that measures sleep quality and disturbances over a one-month recall period. It contains 19 items and measures seven components of sleep quality: subjective sleep quality, sleep latency, sleep efficiency, sleep duration, sleep disturbances, use of sleep medication, and daytime dysfunction. The PSQI global score is the sum of the seven component scores and ranges from 0 to 21, with the higher score indicating worse sleep quality. A global PSQI score of at least 6 points can be used as a cutoff to indicate poor sleep quality, with a diagnostic sensitivity of 89.6% and specificity of 86.5% 21. Consistent with the empirically established minimal clinically important difference (MCID) for the PSQI global score in pain populations 24,25, sleep response was defined as an improvement (decrease) of at least 3 points in the PSQI global score from baseline at ten weeks 26. Remission of sleep disturbance was defined as a posttreatment PSQI global score of no greater than 5 points at ten weeks 27–29.
The BPI is an 11-item pain assessment tool validated for use among patients with cancer. It measures the intensity of pain (four items) and interference (seven items) of pain in the patient’s life. The BPI pain severity score is calculated as the average score on the four pain intensity items (range 0 to 10) and is a secondary outcome for this analysis. The BPI psychometrics are well-established (Cronbach’s alpha 0.80–0.87 for the four pain severity items and 0.89–0.92 for the seven interference items) 30. Consistent with established definitions of analgesic response based on the BPI, we considered a reduction of 30% or greater on the BPI pain severity score from baseline to ten weeks to be an analgesic response 18,31.
Statistical Plan:
Demographic and baseline clinical characteristics were summarized with descriptive statistics. We summarized continuous variables (age, baseline PSQI global score, baseline BPI pain severity score, years since cancer diagnosis, and duration of pain) using means and standard deviations. We summarized categorical variables (sex, race, cancer type, cancer treatment, and pain medication use) using frequencies and percentages.
For sleep outcomes, our primary hypothesis was, among people with poor sleep quality and moderate-to-severe chronic musculoskeletal pain at baseline, electroacupuncture or auricular acupuncture compared to usual care would lead to significant improvements in sleep quality measured by the PSQI global score at ten weeks. We analyzed PSQI scores over time using a constrained linear mixed model in which we constrained the treatment arms to have a common baseline mean 32, reflecting the pre-randomization timing of the baseline assessment. The model included the randomization stratification variables (accrual site [Manhattan/Regional] and baseline opioid use [Yes/No]), treatment arm, time (categorical), and the arm-by-time interaction as fixed effects and patient-specific random intercepts. Results are reported as least-squares means, mean differences, and confidence intervals, with inferences based on model coefficients and contrasts of model-adjusted means. Inferences regarding differences between arms at weeks 10 and 24 were based on model coefficients for the arm-by-time interaction. Similar models were used to analyze the PSQI component scores. We used chi-square and Fisher’s exact tests to compare the proportions of patients with week 10 sleep response and full sleep disturbance remission at week 10 across treatment arms.
Among the two acupuncture arms, we compared PSQI global scores over time by BPI response, and BPI pain severity scores over time by sleep response using linear mixed models predicting the outcome using the three-way interaction (and all lower-order terms) between treatment arm (electroacupuncture vs. auricular acupuncture), week (categorical), and treatment response (pain response or sleep response, depending on the model).
A p-value less than 0.05 was considered statistically significant. The sample size of the parent trial was selected to yield 80% power for evaluating the primary outcome while maintaining an overall Type I error rate of 5% for the comparisons. Data analysis was performed using R version 4.1.2 33.
RESULTS
Study Population
Of 360 randomized patients from the parent trial, 268 patients (mean [SD] age, 61.4 [12.6] years; 191 women [71.3%] and 77 men [28.7%]; mean [SD] PSQI global score, 10.3 [3.3] points; mean [SD] BPI pain severity score, 5.3 [1.7] points) were included in this analysis (Figure 1). Baseline characteristics, including age, sex, race/ethnicity, cancer types, active treatments, pain types, duration of pain symptoms, pain severity, pain medication use, and sleep quality, were similar across the three groups (Table 1). Further, baseline sleep disturbance measured by the PSQI global score was significantly correlated with the BPI pain severity score at baseline in patients of three groups combined (R = 0.2; P<0.001)(Figure S1–Supplementary material).
Figure 1. Study flow diagram.
Table 1.
Demographic and Clinical Characteristics of PEACE Patients with Sleep Disturbance at Baseline (N=268)
| Characteristics | Electroacupuncture (n=110) | Auricular Acupuncture (n=110) | Usual Care (n=48) |
|---|---|---|---|
|
| |||
| Age1 | 60.2 (13.7) | 62.8 (11.5) | 61.0 (12.7) |
|
| |||
| Sex | |||
| Male | 32 (29.1) | 35 (31.8) | 10 (20.8) |
| Female | 78 (70.9) | 75 (68.2) | 38 (79.2) |
|
| |||
| Race | |||
| Non-white | 33 (30) | 29 (26.4) | 10 (20.8) |
| White | 77 (70) | 81 (73.6) | 38 (79.2) |
|
| |||
| Ethnicity | |||
| Hispanic | 13 (11.8) | 10 (9.2) | 3 (6.2) |
| Non-Hispanic | 97 (88.2) | 99 (90.8) | 45 (93.8) |
|
| |||
| Cancer type | |||
| Breast | 46 (41.8) | 55 (50.0) | 24 (50.0) |
| Prostate | 9 (8.2) | 14 (12.7) | 4 (8.3) |
| Colorectal/GI | 5 (4.5) | 2 (1.8) | 2 (4.2) |
| Lymphoma | 19 (17.3) | 15 (13.6) | 5 (10.4) |
| Melanoma | 5 (4.5) | 4 (3.6) | 2 (4.2) |
| Lung | 5 (4.5) | 6 (5.5) | 0 (0.0) |
| Other | 21 (19.1) | 14 (12.7) | 11 (22.9) |
|
| |||
| Cancer treatment | |||
| Surgery | 81 (73.6) | 79 (71.8) | 39 (81.2) |
| Chemotherapy | 45 (40.9) | 46 (41.8) | 19 (39.6) |
| Radiation | 52 (47.3) | 61 (55.5) | 23 (47.9) |
| Reconstructive surgery | 19 (17.3) | 19 (17.3) | 9 (18.8) |
| Biological/Immunotherapy | 4 (3.6) | 8 (7.3) | 1 (2.1) |
| Bone marrow transplant | 1 (0.9) | 3 (2.7) | 0 (0.0) |
| Hormonal | 33 (30) | 27 (24.5) | 17 (35.4) |
|
| |||
| Year since cancer diagnosis1 | 6.0 (6.3) | 6.1 (6.7) | 6.0 (6.2) |
|
| |||
| Baseline global PSQI score1 | 10.4 (3.5) | 10.2 (3.0) | 10.1 (3.4) |
|
| |||
| Baseline BPI severity score1 | 5.3 (1.8) | 5.2 (1.7) | 5.7 (1.5) |
|
| |||
| Taking any pain medications | 69 (63.9) | 65 (61.9) | 36 (76.6) |
|
| |||
| Duration of pain symptoms, years1 | 6.1 (7.0) | 5.0 (6.6) | 5.3 (6.0) |
|
| |||
| Number pain medication | 69 (63.9) | 65 (61.9) | 36 (76.6) |
Data are presented as n (%) except for 1 age, year since cancer diagnosis, baseline global PSQI score, baseline BPI severity score, duration of pain symptoms, all expressed as mean with standard deviation.
Key: GI = gastrointestinal; PSQI = Pittsburgh Sleep Quality Index; BPI = Brief Pain Inventory
Sleep Improvements by Treatment Arms and the Relationship Between Sleep and Pain in Response to Treatment
The difference in the PSQI global score between electroacupuncture versus usual care was 1.42 points (95% CI, 0.45 to 2.38; P=0.004; Cohen’s d=0.37), and between auricular acupuncture versus usual care, 1.59 points (95% CI, 0.62 to 2.55; P=0.001; Cohen’s d=0.45) (Figure 2 and Table 2). Compared with baseline, the PSQI global score was 1.79 points (95% CI, 1.25 to 2.34; P<0.001) lower at ten weeks in the electroacupuncture group, 1.96 points (95% CI, 1.41–2.51; P<0.001) lower in the auricular acupuncture group, and 0.37 points (95% CI, −0.45 to 1.20, P=0.37) lower in the usual care group. From baseline to 24 weeks, the PSQI global score was reduced by 1.96 points (95% CI, 1.42 to 2.50; P<0.001) in the electroacupuncture group, and by 2.32 points (95% CI, 1.75 to 2.88; P<0.001) in the auricular acupuncture group. There was no significant difference in the PSQI global score between electroacupuncture and auricular acupuncture: 0.17 points (95%CI, −0.58 to 0.91; P=0.66) at 10 weeks, and 0.36 points (95%CI, −0.40 to 1.11; P=0.36) at 24 weeks. Both treatments significantly improved the PSQI subscale overall sleep quality and sleep disturbances scores compared to usual care, from baseline to ten weeks (Table 2).
Figure 2. Global Pittsburgh Sleep Quality Index (PSQI) score over 24 weeks by treatment.
The PSQI is a 19-item self-rated questionnaire that measures sleep quality and disturbances over a one-month period. The global PSQI score ranges from 0 to 21, with a higher score indicating worse sleep quality.
Key: EA = electroacupuncture; AA = auricular acupuncture; UC = usual care
Table 2.
Change in Sleep and Pain Outcomes from Baseline by Treatment
| Outcomes | Within-group changes in PSQI from baseline Mean (95% CI) |
Between-group differences in PSQI change from baseline Mean (95% CI) |
||||
|---|---|---|---|---|---|---|
| EA | AA | UC | EA vs UC | AA vs UC | EA vs AA | |
| Primary Outcome | ||||||
| PSQI Global Score | ||||||
| Week 10 | −1.79 (−2.34 to −1.25) | −1.96 (−2.51 to −1.41) | −0.37 (−1.20 to −0.45) | −1.42 (−2.38 to −0.45) | −1.59 (−2.55 to −0.62) | 0.17 (−0.58 to 0.91) |
| Week 24 | −1.96 (−2.50 to −1.42) | −2.32 (−2.88 to −1.75) | NA | NA | NA | 0.36 (−0.40 to 1.11) |
| Secondary Outcomes | ||||||
| PSQI - Subjective Sleep Quality | ||||||
| Week 10 | −0.37 (−0.49 to −0.24) | −0.39 (−0.52 to −0.26) | −0.12 (−0.31 to 0.06) | −0.25 (−0.46 to −0.03) | −0.27 (−0.48 to −0.05) | 0.02 (−0.15 to 0.19) |
| Week 24 | −0.41 (−0.54 to −0.29) | −0.41 (−0.54 to −0.28) | NA | NA | NA | 0 (−0.18 to 0.17) |
| PSQI – Subjective Sleep Latency | ||||||
| Week 10 | −0.27 (−0.42 to −0.12) | −0.48 (−0.64 to −0.33) | −0.03 (−0.25 to 0.20) | −0.24 (−0.50 to 0.02) | −0.46 (−0.72 to −0.19) | 0.22 (0.01 to 0.42) |
| Week 24 | −0.26 (−0.41 to −0.12) | −0.40 (−0.56 to −0.25) | NA | NA | NA | 0.14 (−0.07 to 0.35) |
| PSQI - Sleep Duration | ||||||
| Week 10 | −0.15 (−0.30 to 0.01) | −0.13 (−0.29 to 0.02) | 0.04 (−0.19 to 0.28) | −0.19 (−0.47 to 0.08) | −0.18 (−0.45 to 0.10) | −0.02 (−0.23 to 0.20) |
| Week 24 | −0.18 (−0.33 to −0.03) | −0.20 (−0.36 to −0.04) | NA | NA | NA | 0.02 (−0.19 to 0.24) |
| PSQI - Habitual Sleep Efficiency | ||||||
| Week 10 | −0.09 (−0.30 to 0.11) | −0.10 (−0.30 to 0.11) | −0.10 (−0.40 to 0.20) | 0 (−0.34 to 0.35) | 0 (−0.35 to 0.35) | 0 (−0.27 to 0.27) |
| Week 24 | −0.17 (−0.37 to 0.03) | −0.46 (−0.67 to −0.25) | NA | NA | NA | 0.29 (0.01 to 0.56) |
| PSQI - Sleep Disturbances | ||||||
| Week 10 | −0.28 (−0.38 to −0.18) | −0.25 (−0.35 to −0.14) | 0.02 (−0.13 to 0.17) | −0.30 (−0.47 to −0.12) | −0.27 (−0.44 to −0.09) | −0.03 (−0.17 to 0.11) |
| Week 24 | −0.31 (−0.41 to −0.20) | −0.27 (−0.38 to −0.16) | NA | NA | NA | −0.04 (−0.18 to 0.10) |
| PSQI - Use of Sleep Medication | ||||||
| Week 10 | −0.31 (−0.51 to −0.12) | −0.29 (−0.49 to −0.10) | −0.03 (−0.32 to 0.26) | −0.28 (−0.62 to 0.06) | −0.27 (−0.61 to 0.07) | −0.02 (−0.28 to 0.25) |
| Week 24 | −0.24 (−0.43 to −0.04) | −0.26 (−0.46 to −0.06) | NA | NA | NA | 0.02 (−0.25 to 0.29) |
| PSQI - Daytime Dysfunction | ||||||
| Week 10 | −0.33 (−0.46 to −0.20) | −0.31 (−0.44 to −0.18) | −0.12 (−0.31 to 0.08) | −0.22 (−0.45 to 0.01) | −0.19 (−0.42 to 0.04) | −0.02 (−0.20 to 0.16) |
| Week 24 | −0.37 (−0.50, −0.24) | −0.37 (−0.51, −0.23) | NA | NA | NA | 0 (−0.18, 0.18) |
Key: PSQI = Pittsburgh Sleep Quality Index; CI = Confidence interval; EA = Electroacupuncture; AA = Auricular acupuncture; UC = Usual care; NA = not available.
The proportion of patients who experienced a 3-point or greater improvement in PSQI global score at ten weeks (“sleep responder”) from baseline was 41.0% (n=41) in the electroacupuncture group, 42.9% (n=42) in the auricular acupuncture group, and 21.4% (n=9) in the usual care group (P=0.044). The proportion of patients who experienced the remission of sleep disturbance at ten weeks was 19.0% (n=19) in the electroacupuncture group and 16.3% (n=16) in the auricular acupuncture group, compared to 2.4% (n=1) in the usual care group (P=0.036).
In addition, among the two acupuncture arms, pain responders had overall greater improvements in sleep quality during treatment and follow-up (P=0.01 for the pain response-by-week interaction). Still, pain outcomes did not differ by sleep responder status (P=0.16 for the sleep response-by-week interaction)(Figure 3).
Figure 3. Global Pittsburgh Sleep Quality Index (PSQI) global score by pain response and Brief Pain Inventory (BPI) pain severity score by sleep response, over 24 weeks.
(a) Pain responders had overall greater improvements in sleep quality during treatment and follow-up (P = 0.01 for the pain response-by-week interaction). (b) Pain outcomes did not differ by sleep responder status during the 24-week period (P = 0.16 for the sleep response-by-week interaction). Pain response is defined as a reduction of 30% or greater on the BPI pain severity score from baseline to 10 weeks. Sleep response was defined as a decrease of at least 3 points in the PSQI global score from baseline to ten weeks.
DISCUSSION
Sleep disturbances are common and debilitating among cancer survivors with pain. This study evaluated improvements in sleep quality associated with acupuncture treatment for pain in cancer survivors with chronic musculoskeletal pain who experienced clinically bothersome sleep disturbances. Both electroacupuncture and auricular acupuncture significantly improved sleep quality from baseline to 10 and 24 weeks while ameliorating pain and demonstrated statistically significant improvements over usual care at the end of treatment. The effects of acupuncture on comorbid sleep disturbance could be attributed to chronic pain relief, as pain responders demonstrated significantly improved sleep quality compared to pain nonresponders. Nevertheless, sleep responders had no greater pain reductions than sleep nonresponders, indicating that response in sleep outcomes is less likely to cause substantial pain reductions.
These results suggest that pain relief from acupuncture may improve sleep quality compared to usual care. These findings add new data to the existing literature on the application of acupuncture for sleep health in cancer survivors. Acupuncture is an established treatment for pain in oncological settings; however, its use in survivorship sleep management is still new and relevant evidence is emerging 34,35. In the general population, acupuncture improves subjective and objective sleep outcomes 36,37. In cancer survivors, trials from Germany and the United States have shown significant insomnia severity improvements following acupuncture treatment 38,39. Consistent with those findings, our study provides focused evidence that both electroacupuncture and auricular acupuncture elicit sleep quality improvement while addressing persistent pain. Given the sleep quality impairment associated with regular pain medication use 40,41 and growing concerns about the combined use of multiple drugs (“polypharmacy”) during cancer survivorship 42, these findings indicate that acupuncture could be a reasonable option for treating sleep disturbance among cancer survivors with pain.
Our study also contributes to the growing understanding of the interactions between pain and sleep disruptions in cancer populations. Pain and sleep disturbance interact reciprocally through common neurobiological pathways, including dopamine and opioid systems 43,44. Epidemiological data indicate that sleep impairment may be a stronger, more reliable predictor of pain occurrence than pain is of sleep impairments 45. Our study offers therapeutic insight into pain-sleep interactions, highlighting that the pain response may predict more pronounced sleep quality improvements during nonpharmacologic treatment, instead of the sleep response predicting pain relief. The concurrent sleep quality improvement may be explained by the regulation of opioid and dopamine secretion by acupuncture in achieving pain relief. This finding is consistent with behavioral studies showing that cognitive behavioral therapy for insomnia (CBT-I) alleviated pain patients’ difficulty sleeping but not pain 46–49. This is also evidenced by a previous study in which we demonstrated that rapid pain relief by manual acupuncture contributed to insomnia improvements among cancer survivors 18. Further research is needed to elucidate the putative underpinning mechanisms of pain-sleep interaction, which is critical to informing the implementation of multitarget strategies for sleep and pain management.
Our study further suggests opportunities for incorporating other evidence-based sleep treatments for cancer patients with pain. Despite sleep quality improvements, the overall magnitude of improvement is small to medium, as judged by Cohen’s D. Only one-fifth of patients experienced a remission of sleep disturbance. Over 50% still did not respond to acupuncture treatment for sleep quality, which opens the door to other evidence-based sleep interventions. Pain is a precipitating factor associated with the onset of insomnia, but over time maladaptive behavioral factors take over and become the determinants of sleep disturbance 50. In practice, people with pain experiencing sleep difficulties should be screened for maladaptive behavioral changes. But they should also be informed of the benefits of targeted sleep approaches for dismissing behavioral factors, as well as how to access them in the real world. Future research needs to determine whether combining pain interventions like acupuncture with behavioral techniques can enhance the treatment of sleep disturbance in patients with pain.
This study has several limitations. First, the findings from the secondary analysis of existing clinical trial data are hypothesis-generating rather than confirmatory. Second, the parent trial was designed to address pain primarily; we did not perform a clinical diagnosis of sleep to know whether the sleep disturbance represents insomnia or other sleep pathology. Further, we did not have measures of sleep medications, sleep diaries, or objective sleep monitoring such as polysomnography and actigraphy. In addition, the parent trial was designed as a pragmatic study without sham control. Therefore, the effects observed between acupuncture interventions and usual care represent overall effectiveness rather than specific efficacy of acupuncture needling efficacy. Also, our study protocols of electro- and auriculo-acupuncture focused on pain as the primary complaint so the impact on sleep quality may not be as optimal as the other forms of acupuncture (i.e. manual acupuncture), which were shown to be more effective at improving sleep in prior research 38. Last, our trial was conducted in urban and suburban settings of an academic medical institution, which limits the generalizability of our results.
CONCLUSION
Among cancer survivors with comorbid sleep disturbance and chronic musculoskeletal pain, electroacupuncture or auricular acupuncture treatments for pain compared with usual care were associated with clinically relevant improvements in sleep quality. They appeared to be attributable to improvements in pain.
Supplementary Material
ACKNOWLEDGEMENTS
We thank the patients who participated in this study and volunteered biological samples. We thank Christina Seluzicki for editorial assistance. We thank all editors and peer reviewers for their time and professional advice on our study.
FUNDING
This work was supported by the Department of Defense office of the Congressionally Directed Medical Research Programs through the Peer Reviewed Medical Research Program Clinical Trial Award (W81XWH-15-1-0245). This work was also supported in part by a National Institutes of Health/National Cancer Institute (NCI) Cancer Center grant (P30 CA008748). Dr. Mao is supported in part by NCI R01 CA240417.
Footnotes
CONFLICTS OF INTEREST
JJM reports a grant from Tibet Cheezheng Tibetan Medicine Co Ltd outside the submitted work. The other authors made no disclosures.
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