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11 Articles in Volume 6, Issue #4
Assessing Secondary Gain In Chronic Pain Patients
Chronic Overuse Sports Injuries
Introducing Low Level Laser Therapy to Pain Management
Managing Diabetic Peripheral Neuropathic Pain (DPNP)
Moral Virtue and the Pain Physician
Non-pharmacologic Therapy for Chronic Opioid-dependent Sickle Cell Pain
Osteoarthritis of the Knee
Smoking and Low Back Pain
Temporal Tendinitis Migraine Mimic
The Underutilization of Intrathecal Treatment
Tumblin’ Dice–Why Does Random Matter?

Non-pharmacologic Therapy for Chronic Opioid-dependent Sickle Cell Pain

Study results confirm the efficacy of Benson's Relaxation Response in reducing pain and medication in this patient population.

Sickle cell anemia is an hereditary hemoglobinopathy, chiefly occurring in African-Americans and is often accompanied by chronic and acute bone and joint pain. An acute exacerbation is known as a crisis wherein the pain can become excruciating and require hospitalization and large doses of injectable opioids. Some sickle cell patients take oral opioid medications chronically in an effort to deal with ever-present pain.

Opioid medications can have many undesirable side effects both physical and mental. These might include lethargy, fatigue, constipation and habituation, as well as many others, and are summarized in Table 1.

Pain, often the most disturbing element of the disease, is a subjective phenomenon that has both physical and mental components. The physical bone pathology is, in fact, the cause of the bone pain that patients experience. However, several factors determine how the pain is perceived. Chief among these is the patient’s individual pain threshold. There are both neurological and psychological factors which contribute to this threshold.

Traditionally, pharmacologic agents have been the mainstay in treating sickle cell pain, while other modalities have received much less attention.

Table 1. Side effects and toxicities of opioids.4
Central Nervous System Lightheadedness, dizziness, sedation, dysphoria, euphoria, weakness, headache, agitation, tremor, uncoordinated muscle movements, seizure, alterations of mood (nervousness, apprehension, depression, floating feelings), dreams, muscle rigidity, transient hallucinations and disorientation, visual disturbance, insomnia, increased intracranial pressure
Gastrointestinal Constipation, nausea, dry mouth, biliary tract spasm, laryngospasm, anorexia, diarrhea, cramps, taste alteration, constipation, ileus, intestinal obstruction, increases in hepatic enzymes
Cardiovascular Flushing of the face, chills, tachycardia, bradycardia, palpitation, faintness, syncope, hypotension, hypertension
Genitourinary Urine retention or hesitance, reduced libido and/or potency
Dermatologic Pruritus, urticaria, other skin rashes, edema, diaphoresis
Other Sweating, antidiuretic effect, paresthesia, muscle tremor, blurred vision, nystagmus, diplopia, miosis, analphlaxis, dependence, and addiction
Table 2. Benson’s Method for Eliciting The Relaxation Response.
  1. Pick a focus word, short phrase, or prayer that is firmly rooted in your belief system.
  2. Sit quietly in a comfortable position.
  3. Close your eyes.
  4. Relax your muscles, progressing from your feet to your calves, thighs, abdomen, shoulders, head and neck.
  5. Breathe slowly and naturally, and as you do, say your focus word, sound, phrase, or prayer silently to yourself as you exhale.
  6. Assume a passive attitude. Don’t worry about how well you’re doing. When other thoughts come to mind, simply say to yourself, “Oh well," and gently return to your repetition.
  7. Continue for ten to twenty minutes.
  8. Do not stand immediately. Continue sitting quietly for a minute or so, allowing other thoughts to return. Then open your eyes and sit for another minute before rising.
  9. Practice the technique once or twice daily. Good times to do so are before breakfast and before dinner.

Review of the Literature

Some interesting studies have been published which examine the non-pharmacologic therapy of sickle cell pain.

In Thomas’ study,1 15 sickle cell patients were given training in progressive relaxation, thermal feedback, cognitive strategies, and self-hypnosis to relieve pain. Results from the study show a 38.5% reduction in the number of emergency room visits, and a 31% reduction in the number of hospitalizations. There was also a 50% reduction in inpatient stays during the six months post training, compared to the six months prior to training. Of significant note, there was a 29% reduction in analgesic intake for regular users.

In a study by Gil et al,2 64 patients with sickle cell disease were randomly assigned to either a cognitive coping skills group (three 45 min sessions of training patients to use 6 cognitive coping strategies) or a disease-education control group (three 45 min didactic discussion sessions about sickle cell anemia). Results indicated that brief training in cognitive coping skills resulted in increased coping skills, decreased negative thinking, and a lower tendency to report pain during lab-induced noxious stimulation.

Children, adolescents, and adult patients with sickle cell disease and who reported experiencing seven or more episodes of vaso-occlusive pain the preceding year, were enrolled in a prospective two-period treatment protocol by Dinges et al.3 Patients were taught self hypnosis, and both pain and sleep patterns were studied. Results indicated that self-hypnosis was associated with a significant reduction in pain days. Additionally, both “bad sleep" nights and the use of pain medications decreased significantly during self-hypnosis. Findings suggested that the overall reduction in pain frequency was due to elimination of less severe episodes of pain. The study clearly demonstrated that an adjunctive behavioral treatment for sickle cell pain, involving self-hypnosis and regular contact with a medical self-hypnosis team, can be beneficial in reducing recurrent, unpredictable episodes of pain in patients for whom few safe, cost-effective medical alternatives exist.

Study Design

This study was an investigation of the effects of the Relaxation Response (R.R) on chronic sickle cell pain in patients requiring chronic opioid analgesics. The R.R. is a term coined by Herbert Benson, M.D. to characterize the body’s response to what is best described as an induced meditative state.5 Table 2 describes the steps Benson used to elicit the R.R.

Adult sickle cell pain patients in an outpatient facility, and who were maintained on chronic oral opioid agents, were invited to participate in the study. The nature of the study was explained and informed consent was obtained. No other criteria, other than the chronic use of opioid agents, were required.

Participating patients filled out a study questionnaire which recorded daily pain levels on a scale of ascending intensity from one to ten along with medication usage over a 30 day period. At the end of 30 days, the patients were taught the R.R. and identical data was collected for the following 30 days. During the second 30 day period, patients performed the R.R. twice daily.

Patient Characteristics

Of the thirty-four patients who were enrolled in the study, five patients failed to report for follow-up or did not keep the required records. Twenty-nine were therefore eligible for the study. These patients ranged in age from 18 to 36 years. Twelve patients were female and seventeen were male and their characteristics are summarized in Table 3.


Table 4 tabulates the daily pain score both before R.R. training (“Baseline"), and following training. The daily average pain score prior to training was 3.1. Following R.R. training, the average daily pain score declined to 2.4. In each case, the average pain score was calculated by dividing the sum of the respective daily pain scores by 30 days. Table 5 tabulates the results of opioid drug use both before and after R.R. training. The average daily opioid drug use was derived by taking the sum of daily opioid use (as measured by pill quantity) divided by 30 days. The average daily opioid pills consumed was 3.8 prior to training and 2.9 following R.R.training


Sickle cell anemia is a chronic and debilitating disease. It is often characterized by both acute and chronic pain. Opioid analgesics are frequently used to treat the pain. Painful crises are almost universally treated with large and frequent doses of opioid analgesics such as Demerol and Morphine. This study focused on chronic pain patients who required opioid analgesics for control of their persistent pain. Recognizing that there is often a psychogenic aspect to pain, this study investigated the efficacy of the R.R. in mitigating chronic sickle cell pain. The results indicate that the R.R. had a significant positive effect on the perception of pain, as measured by the decrease in the daily average pain score, and the decrease in the daily opioid use score.

Lessening the need for opioid pain medication is a desirable goal since opioid medications can have many undesirable side effects (see Table 1). Aside from the side effects, there is also the issue of diversion and possible misuse of the medication by patient.

This study confirms the finding of prior studies that sickle cell pain is susceptible to mitigation by non pharmacologic modalities having no known—or even contemplated—negative side effects.

The reason R.R. works to modify pain is not known at this time. It is possible that the technique somehow modulates or blocks the perception of pain. Another possibility is that the R.R. may stimulate the release of endorphins which serve as natural analgesics.

Potential problems with this study included the use of each patient as their own control and that the study was not blinded. Given the nature of the disease under study and the nature of the intervention—a form of meditation—it would be difficult, if not impossible, to design a controlled, blinded study of the efficacy of the R.R.

Table 3. Patient Characteristics
Number of patients entered in the study ............. 34
Number of patients meeting requirements ............ 29
Age Range ........................................ 18-36
Sex ............................................. 12/29 F 17/29 M
Table 4. Daily Pain ScoreProlotherapy
Patient # Baseline Following training
1 3 3
2 4 3
3 2 2
4 1 1
5 4 2
6 6 4
7 3 2
8 2 2
9 1 1
10 3 2
11 4 3
12 2 2
13 4 3
14 6 5
15 2 2
16 1 1
17 4 2
18 4 4
19 3 1
20 6 4
21 4 3
22 1 1
23 3 3
24 7 7
25 3 2
26 2 2
27 1 1
28 4 3
29 3 3
Totals 93 74
Average Daily Pain Score
  93/30=3.1 74/30=2.4
Table 5. Daily Opioid Drug Use (Pills Per Day)
Patient # Baseline Following training
1 4 3
2 3 3
3 1 2
4 6 4
5 3 3
6 8 7
7 1 1
8 4 2
9 5 3
10 7 4
11 2 2
12 4 3
13 6 5
14 5 5
15 7 5
16 2 2
17 1 2
18 4 3
19 5 2
20 6 4
21 5 3
22 2 1
23 4 2
24 3 3
25 7 5
27 5 5
28 3 2
29 2 2
Totals 115 88
Average Daily Opioid Pills
  115/30=3.8 88/30=2.9


The results of this study confirm that non-pharmacologic interventions can positively affect the chronic pain experienced by sickle cell patients. In fact, the relaxation response technique was found to be successful in mitigating the chronic pain associated with sickle cell anemia and lessening the need for oral opioids in patients on chronic opioid therapy.

While Benson’s classical R.R. was used in this study as the non-pharmacologic intervention, it’s possible that other forms of meditation and/or hypnosis may be as effective or, perhaps, even more effective. Future studies should be designed to define what non-pharmacologic modalities work best.

Finally, this study did not involve patients in crisis. Would the R.R. be useful in this setting? Future studies are needed to answer this question. However, at this point it can be suggested that all sickle cell patients be taught non-pharmacologic methods to help them cope with their pain.

Last updated on: December 20, 2011
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