Acupuncture for chronic pain in adults with sickle cell disease: a mixed-methods pilot study

Abstract

Objective:

Chronic pain is a common symptom experienced among patients with sickle cell disease (SCD). Our aims were to assess the feasibility and acceptability of performing acupuncture for the treatment of chronic pain in adults with SCD.

Methods:

This was a single-arm, prospective pilot study of six adults with SCD. Participants reported ≥ 3 months of chronic pain and were > 18 years of age. Per protocol, acupuncture was to be administered twice per week for 5 weeks, for 30 min per session. All treatments were performed in the acupuncture treatment laboratory at the University of Illinois Chicago College of Nursing. Pain intensity, pain interference, and other symptoms were measured at baseline and after the intervention. Participants completed a semi-structured interview and a protocol acceptability questionnaire after the acupuncture intervention.

Results:

Six participants (mean age 52.5 years, six Black) were enrolled. Although the study was suspended due to COVID-19 and not all participants completed the 10-session protocol, completion rates were high with no missed appointments. One participant did not complete the study due to hospitalization unrelated to acupuncture. No adverse events were reported. At completion of the intervention at 4–5 weeks post-baseline, all participants had reduced pain intensity and pain interference. The mean acceptability score on the protocol acceptability questionnaire was 82%.

Conclusion:

It was feasible and acceptable to implement acupuncture in adults with SCD. This study can be used to guide a larger randomized controlled trial to evaluate the effect of acupuncture on reducing chronic pain in adults with SCD.

Trial registration number:

NCT04I56399 (ClinicalTrials.gov)

Introduction

Sickle cell disease and pain

Sickle cell disease (SCD) refers to several hemoglobin disorders, each with a mutation in the β-hemoglobin chain. SCD is the most common genetic blood disorder in the world, with millions suffering globally. Approximately 100,000 people in the United States, mainly of African and Hispanic background, are living with SCD.¹ In the United States, the costs of medical care for SCD are estimated to be over $2.4 billion annually.² Pain is ever present for those with SCD and is the most common diagnosis for those admitted to the Emergency Department and hospital. For many years, SCD pain was primarily thought to be acute and related to vaso-occlusion;³ however, it has become increasingly clear that adults with SCD experience chronic pain.^3,4 Pain in SCD is complex and is often associated with and exacerbated by anxiety and stress.⁵ At present, opioids are commonly used to manage SCD pain but are associated with possible addiction and multiple side effects.⁶ Also, there is a lack of adequate control of chronic pain.⁶ To address these gaps, the aim of this pilot study was to establish the feasibility and acceptability of acupuncture for the treatment of chronic pain associated with SCD and its negative sequelae. It was anticipated that the results of this study would be used to provide preliminary feasibility data for a larger funded efficacy trial of acupuncture for adults with SCD.

Acupuncture for the treatment of chronic pain

There is growing evidence that acupuncture can effectively treat chronic pain. In 2018, a large meta-analysis (n = 20,827 participants) that systematically assessed the effect of acupuncture using data from 39 high-quality randomized trials of patients with one of four chronic pain conditions (nonspecific musculoskeletal pain, osteoarthritis, chronic headache, and shoulder pain) showed a significant effect.⁷ Study designs included verum acupuncture versus either sham acupuncture or no acupuncture as a control. Regardless of pain condition, the results indicated that acupuncture significantly reduced pain compared to sham acupuncture or usual care (all p < 0.001). To our knowledge, this was the first meta-analysis to determine the effectiveness of acupuncture for the treatment of other chronic pain conditions.

Acupuncture for the treatment of SCD

Evidence of the efficacy of acupuncture for the treatment of SCD is promising but requires further study. Among the six studies that used acupuncture for the treatment of SCD pain, all showed that acupuncture reduced pain.⁸⁻¹³ Three studies focused on pediatric populations and included a case study,⁸ a study of two patients,⁹ and a retrospective uncontrolled trial of 12 patients.¹⁰ Three studies examined the use of acupuncture for the treatment of adults with SCD.AW The first was an uncontrolled retrospective review in which a total of 24 inpatient and outpatient adults were treated during acute vaso-occlusive crises using individualized traditional acupuncture point prescriptions.¹¹ In this study, nine inpatients received a median of three treatments and had a reduction in pain of 2.1 on a 0–10 pain rating scale, and 15 outpatients received a median of four treatments and had up to a 75% reduction in pain. The second study of adults with SCD was uncontrolled and treated 10 adults with a total of 16 acute vaso-occlusive crises; participants reported a decrease in pain in 15 of 16 acute vaso-occlusive crises.¹² The third was a report of five cases of adults with SCD who did not experience any pain after acupuncture.¹³

In preparation for a larger randomized controlled trial (RCT) to assess the effectiveness of acupuncture for the treatment of SCD pain, we conducted a pilot study to investigate feasibility and acceptability in terms of: (1) acupuncturist training to learn a standardized acupuncture protocol for the treatment of SCD; (2) acupuncturist implementation of the protocol; (3) participant enrollment and retention; (4) participant completion of study measures; and (5) acceptability to participants, measured using scale scores and qualitative interviews.

Methods

Design, setting, and participants

This was a single-arm, prospective pilot study conducted with adult patients attending a SCD clinic that is part of the University of Illinois Chicago (UIC) Hospital Health Sciences System (UI Health). With more than 800 patients, most of whom are Black (95%), UI Health has one of the largest SCD programs in the Midwest. In 2017, over 75% of patients had either public insurance or were uninsured, and 99% reported being at or below 200% of the poverty income level. To meet the inclusion criteria, participants needed to be: (1) adults with SCD who reported ≥ 3 months of chronic pain; (2) ≥ 18 years of age; (3) have no cognitive impairment; and (4) be able to speak and read English. We developed our inclusion criteria based on the fact that adults with SCD have a high burden of chronic pain.^14,15 Participants were recruited from 14 January 2020 to 18 February 2020. This study was approved on 4 November 2019 by the UIC institutional review board (IRB; protocol no. 2019–1077) and registered at ClinicalTrials.gov (ref. NCT04156399) on 7 November 2019.

Acupuncture intervention

The acupuncture study intervention was developed according to the Standards for Reporting of Controlled Trials in Acupuncture (STRICTA) guidelines.¹⁷ Traditional acupuncture points were selected as treatment locations based on Traditional Chinese Medicine (TCM) meridian theory,¹⁸ with the goal of pain mitigation and to reduce the anemia of sickle cell anemia.¹⁹ All participants with SCD received a standardized 18-point acupuncture protocol with needle insertion starting superiorly and moving inferiorly down the body (Figure 1). Participants were needled using manual stimulation until de qi sensation was obtained. A singlesize Korean (DBC™) 0.25 × 40 stainless-steel acupuncture needle with wound stainless steel head was used for all needle insertions. Traditional acupuncture point locations used (with depths of needling) were: CV17 (0.5 cun), CV6 (1 cun) and bilateral PC6 (0.5 cun), LI4 (1 cun), SP6 (1 cun), SP10 (1 cun), ST36 (1 cun), LR3 (0.5 cun), LR8 (1 cun), and KI3 (0.5 cun). CVV7 was needled transversely and all other points perpendicularly. The protocol dictated that participants receive two acupuncture treatments each week for 5 weeks, for a total of 10 treatments. The intervention was delivered by four licensed acupuncturists. All acupuncturists were National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM) certified with an average of 14 years of practice experience. They were instructed and monitored by the research specialist in all aspects of the acupuncture protocol to ensure study fidelity including the use of clean needle technique, needle insertion using a tapping in technique, an even rotation every 10 min for stimulation, and the putative importance of “closing the point” during needle removal. After the tenth acupuncture treatment, the subject completed the data collection tools. The research specialist and the acupuncturists monitored each participant for signs of needle shock and other side effects, such as bruising and dizziness. If adverse events occurred, they were documented in an adverse event log. No comparator group was used as the aim of this study was to demonstrate the feasibility of using acupuncture in a future funded efficacy trial of adults with SCD.

Figure 1.

Standardized acupuncture protocol for the treatment of sickle cell disease. Permission was obtained from “The Journal of Chinese Medicine Publications” to reproduce this figure.¹⁶

Data collection

The primary providers at the SCD clinic determined if a patient was a candidate for the study based on the study inclusion criteria and described the study during clinic visits. Patients who expressed an interest in the study met with a research team member, who explained the study using an IRB-approved script based on the inclusion criteria, answered questions, and obtained written informed consent. Upon consent, an appointment was set up for the first acupuncture treatment. At the first treatment visit, participants completed baseline questionnaires prior to the insertion of the acupuncture needles. After the last acupuncture session, participants completed questionnaires and participated in a semi-structured in-person or phone interview to capture their experience to add to our acceptability assessment. The interviews were conducted by the principal investigator (J.M.S.) who was guided by nine questions (see supplemental material). These questions captured personal insights into treatment processes and impact on their pain. Each interview lasted approximately 30 min. After the interview, a co-investor (C.L.P.) who is an expert in qualitative analysis, transcribed the interview; she and the principal investigator performed the qualitative analysis.

Measures

Self-reported sociodemographic characteristics (i.e. age, sex, race, employment status, comorbidities, marital status, number of household members, annual income, and educational attainment of participants) were collected at baseline (T1) prior to the insertion of the acupuncture needles. Symptoms were measured at Tl and also after the completion of the acupuncture treatments (T2).

Patient-reported outcomes measurement information system (PROMIS) measures were used to assess perceptions of pain intensity,²⁰ pain interference,21 depressive symptoms,²² anxiety,^22,23 emotional distress–anger,²² sleep disturbance,²⁴ and fatigue over the preceding 7 days. The PROMIS measures may be viewed at https://www.health-measures.net/explore-measurement-systems/promis. PROMIS measure results are reported as T-scores. The T-score, where 50 is the mean of the general population and 10 is the standard deviation, was generated for each of the PROMIS measures. Higher T-scores represent worse symptoms. The PROMIS measures demonstrate excellent validity across clinical contexts and high internal consistency across diverse racial-ethnic groups (Cronbach’s α 0.92–0.96).^21,25,26

The protocol acceptability scale for treating SCD with acupuncture^27,28 was used to assess the acceptability of all study measures being completed after the last acupuncture session (supplemental material). It is a 10-item self-reported measure, with scores ranging from 0 to 20, used to assess the study acceptability to the participants. This acceptability scale is reliable and valid and has been used in other studies with stable test–retest reliability.^27,28 The study protocol is deemed acceptable if the total mean acceptability scale score is higher than 80% of the maximum score.

Following a topic guide that included questions about rationale for participation, impact on pain, and desire to continue acupuncture as a treatment for pain, we used semi-structured interviews to pragmatically inform the next steps of our research and assess the acceptability of acupuncture from the participant’s perspective.^29,30 Interviews were audio-recorded and transcribed anonymously into text. A deductive and practical analysis was applied to provide personal insights about the participants’ experience with acupuncture treatment.

Quantitative and qualitative analysis

Descriptive statistics (frequency, percentage, means, and standard deviations) were summarized at baseline. We reported pain intensity, pain interference, and other pain-related outcomes before and after the acupuncture intervention. Each transcribed interview was read several times. For the analysis, each major topic area was assessed and compared across participants to identify similar and divergent perspectives and experiences with the acupuncture treatment.

Results

We screened nine potential participants and six met eligibility requirements. These six, who had a moderate to severe level of pain (≥3 on 0–10 scale) within the preceding 3 months, were recruited over a 4-week period. Their average age was 52.5 years (range 36 to 62). All six were Black (100%). Characteristics of the sample are displayed in Table 1. When participants were asked to explain their interest and willingness to participate in this study, their familiarity with acupuncture varied. However, all who agreed to participate were open to alternative ways to treat their pain. Even though one woman, aged 36, said, ‘T have not heard of it [acupuncture] before,” she was curious and willing to participate. Another participant, aged 52, was curious but familiar with acupuncture. She expressed her openness to acupuncture when she said, “I was looking for other ways for treatment of my disease. And I always wanted to try acupuncture.” Another woman, aged 43, was very familiar with acupuncture and its potential. She described acupuncture as “an ongoing process, just like the medication is.” She also saw value in acupuncture’s potential for reducing the use of medications when she said,

Table 1.

Characteristics of the sample (n = 6).

Chara cteristic	Mean ± SD or n (%)
Gender
Female	6(100)
Age (years)	52.5 ± 10.9
Race
Black	6(100)
Highest education
Less than hígh school	2 (333)
Some college or associate degree	3 (50.0)
Bachelor’s degree or higher	1 (16.7)
Income
Less than US$40,000	5 (83.3)
Between US$40,000 and US$50,000	1 (16.7)
Married/partnered
Yes	1 (16.7)
No	5 (83.3)

SD: standard deviation.

But I’d rather do acupuncture than to take medication … Because the medication does other harmful stuff to your body, kidneys, liver. You don’t want to be addicted to pain medication. If you do the acupuncture, it is like that. I feel it is much more better for the long term.

Even though all patients experienced pain relief after acupuncture treatment, not all were certain that they would continue to use acupuncture in the future. When asked whether they would or would not later get acupuncture, and the reason, two participants did not think they would get acupuncture. For example, one participant, aged 60, said, “I don’t like the stick.” Another participant, aged 36, reported feeling sore after acupuncture so was ambivalent about future use. She said, “My body was like really aching. My legs were sore, my arms were sore, my hands were sore.” Another participant also mentioned feeling sore, but said she would still continue getting acupuncture anyway because of the relief it brought. She said,

Of course, I would continue getting it for the pain. I noticed that it helped me using muscles I never used before, so somethings after that, I have ache, I felt that I worked out too much. And that is coming from the energy I have.

Two participants completed all 10 sessions. Four participants did not complete all the sessions. One of the four did not complete the study due to hospitalization unrelated to acupuncture and requested to return when her health stabilized. Three of the four were unable to complete the study due to its suspension because of the COVED-19 public health crisis; two participants received nine sessions and one received eight sessions.

Several logistical issues emerged during this study. We learned that two of the SCD participants were fatigued and/ or had difficulty walking due to chronic back pain or muscle spasticity after a stroke. At the beginning of the study, they stated it was difficult to walk from the parking lot across the street to their acupuncture appointments. We then ensured closer parking spaces were provided. Two participants experienced pain at home, and each had one visit rescheduled. Another two participants experienced pain at home and each had two visits rescheduled.

Pain intensity, pain interference, and pain-related outcomes at baseline and post-intervention are displayed in Table 2. All five participants reported reductions in T-scores for pain intensity (−7.1), pain interference (−9.9), sleep disturbance (−6.8), anxiety (−4.6), depression (−1.6), and anger (−1.0). None of the participants reported adverse events during their treatments. For the protocol acceptability scale for treating SCD with acupuncture, the mean acceptability score was 82%, just over the >80% criterion.

Table 2.

Reported PROMIS outcomes before and after the acupuncture intervention (n = 5).

Outcome	Participant ID	Baseline T-score	Post-test T-score
Pain intensity		49.4 ± 3.4	42.3 ± 7.1
	1	49.9	42.6
	2	52.3	49.9
	3	43.6	30.7
	4	51.3	45.7
	5	49.9	42.6
Pain interference		63.3 ± 4.6	53.4 ± 8.9
	1	61.3	58.7
	2	63.5	61.4
	3	70.2	38.7
	4	63.9	52.6
	5	57.7	55.8
Fatigue		54.6 ± 7.2	55.6 ± 3.9
	1	49.4	50.8
	2	61.0	57.5
	3	49.4	57.2
	4	63.7	52.4
	5	49.4	60.3
Sleep disturbance		54.4 ± 2.8	47.6 ± 11.1
	1	55.5	50.2
	2	54.3	54.3
	3	58.6	35.7
	4	51.8	36.7
	5	51.8	61.2
Depression		55.0 ± 4.6	53.4 ± 8.2
	1	48.8	46.0
	2	54.4	59.3
	3	60.6	56.9
	4	58.0	43.3
	5	53.0	61.5
Anxiety		58.1 ± 5.2	53.5 ± 4.7
	1	55.1	53.1
	2	59.6	60.5
	3	64.9	53.9
	4	59.7	47.2
	5	51.2	52.9
Anger		52.0 ±6.3	51.0 ± 7.6
	1	52.6	42.1
	2	54.5	58.8
	3	58.8	59.1
	4	52.6	48.5
	5	41.7	46.4

All summary data are mean ± SD.

When asked to reflect on their acupuncture experience and its impact on their pain experiences, the five participants who completed post-test measures noted that acupuncture seemed to help them. For example, one participant, aged 52, said,

[S]ince I started the acupuncture study; it seems it reduces the pain at night, and I am able to sleep well. So, I think my body reacts to it well as far as on the pain level … It affected my pain quite tremendously. I was surprised because some of the treatments I [am] used [to], and pain medicine, I got no results. But like I said, for acupuncture, it allowed me to have better rest at night.

Several participants reiterated that acupuncture positively affected their sleep. One participant, aged 43, reported experiencing better sleep. She said,

It helped my sleep without taking sleep aids, my digestion system, helps me to go to bathroom, [I’m] not constipated all the time … I feel more relaxed after getting acupuncture … I would continue getting it for the pain.

One woman, aged 36, linked the treatment to fewer pain crises and felt like she needed less pain medication. She said,

I thought it was amazing, because I had no pain crisis, I was not in no type of pain afterwards … Acupuncture is not hooked up to no type of machine, and [they] just stick needles all over your body and it is a wonderful, great feeling. But if I go to the emergency room, they got to hook me up to an IV, they got to give me morphine and all that different type of medicine. But I tell you it is better than morphine, better than anything that I have really had to take … I [felt] very relaxed … and then I slept during the whole night. My body was … it was like the way it used to be. I was like very calm.

One woman, aged 62, slept better, felt more relaxed and calm, and reduced her anti-depressant medication. She said,

I slept well. Before, I slept couple of hours and wake up. Now, I sleep more 6 hours. That is from the acupuncture. And my depression, get much better, my mood. That is the biggest thing. I was on two anti-depressants. My depression was so severe, I need to take medication to keep it. Even then, if I miss a dose, I can feel my mood change. But with acupuncture, I get rid of one of my anti-depressants. I just stop taking it. I’m feeling good.

Discussion

This acceptability and feasibility study demonstrated that implementation of acupuncture with SCD patients is indeed feasible and acceptable. We had a 67% response rate of those who were approached and enrolled in the study and we retained 83%. Most SCD participants were curious about acupuncture and wanted to try a non-pharmacological method to reduce their pain. Multiple trained acupuncturists implemented the standardized 18-needle acupuncture protocol for the treatment of SCD with no deviations. The participant acceptability criterion was met. It was feasible to enroll and retain most participants to complete all study measures.

We found similar logistical issues as Myers et al., who used relaxation training and massage therapy to treat adults with SCD.³¹ Our participants had transportation difficulties, unpredictable pain episodes, and a need to have their visits rescheduled because they were in pain at home. Thus, convenient parking, ensuring an accessible study location, and prioritizing flexibility in rescheduling acupuncture sessions are critical factors to be considered when planning future studies in adults with SCD.

Our quantitative and qualitative findings showed that SCD participants subjected to this acupuncture protocol experienced a reduction in chronic pain. This result is consistent with the three previous studies of acupuncture for the treatment of pain in adults with SCD.^11–13 Also, various populations of adults with SCD, for example, African Americans versus Africans, may not have the same response to acupuncture treatment, which could be due to underlying pathobiology, as demonstrated in transgenic sickle mice.³² Future research is needed to identify inter-individual differences in response to acupuncture for different genders. In addition, reductions in depression, anxiety, anger, and sleep disturbance were reported in our study Tsai et al.⁹ also found a reduction in pain as well as anxiety after acupuncture in a case study of one child with SCD. Sleep disturbance and depression have been reported as common concerns among patients with SCD patients, especially in patients with frequent pain.³³ It has also been reported that chronic pain can negatively influence physical function and mental health in patients with SCD.³⁴ Thus, it is valuable to evaluate whether this acupuncture protocol for the reduction of pain can also improve pain-related symptoms and comorbidities such as sleep disturbance, depression, and anxiety in adults with SCD.

A limitation of our study was its high risk of selection bias. During the recruitment phase, physicians pre-screened eligible subjects for the research assistant, which may have resulted in selection bias. The small sample size and one-armed design reduced our ability to test the significant changes of pain intensity, pain interference, fatigue, sleep disturbance, depression, anxiety, and anger before and after the acupuncture intervention, such that generalizability of the study outcome measures cannot be inferred for all adults with SCD. Future studies are needed with larger sample sizes and more than one allocation group to test the efficacy of acupuncture with respect to reducing pain and associated symptoms in adults with SCD. Another limitation was the inability to complete all acupuncture sessions due to the COVID-19 pandemic.

In conclusion, our study suggested that it appears feasible and acceptable to implement our acupuncture protocol in adults with SCD. This study is being used to guide a larger RCT to evaluate the effect of acupuncture on chronic pain and associated symptoms in adults with SCD.