Chronic pain

Background
In SCD, pain is considered chronic if it lasts more than 3 months. People with SCD experience both nociceptive and neuropathic pain. Nociceptive pain is a hallmark of acute pain (see the “Managing Acute Complications of Sickle Cell Disease” chapter). Chronic pain, including that described in people without SCD, is often associated with neuropathic pain. The pathology of the transformation from chronic nociceptive pain to neuropathic pain is not well understood. The Pain in Sickle Cell Epidemiology Study (PiSCES) showed that adults reported chronic SCD pain at home during about 55 percent of the 31,017 days surveyed. Similarly, children reported SCD pain at home on about 9 percent of the 1,515 days surveyed.288 In the Multicenter Study ofHydroxyurea in Sickle Cell Anemia (MSH), at-home analgesics were used for SCD pain on 40 percent of diary days and during 80 percent of 2-week followup periods, with oxycodone and codeine being used most frequently.

The major types of SCD-associated chronic pain include the following:

Chronic pain often of unclear etiology. This type of chronic sickle cell pain may be an extension of recurrent acute painful episodes. Therefore, early and aggressive intervention in treating acute sickle cell pain may reduce the development of chronic pain.

Chronic pain in a specific tissue or organ, such as avascular necrosis (AVN) of the hips, or leg ulcers. Chronic SCD pain is usually described as constant and deep, nagging, and achy in nature. It can occur in the chest, back, abdomen, extremities, neck, or head and is difficult to treat.

Chronic neuropathic pain. This is usually described as burning, numb, tingling, lancinating, shooting, or paroxysmal in nature and is associated with a sensation of pins and needles. Its severity is also enhanced by exposure to either cold or heat. This pain can be secondary to either peripheral or central nerve injury or nerve dysfunction. SCD-related neuropathic pain has two etiologies. The first is tissue damage secondary to occlusion of blood vessels that supply the nerves as can be found in mental nerve neuropathy and spinal cord infarction. The second seems to be chronic pain. Persistent chronic pain, the resulting inflammation, and/or pain management seem to lead to neuropathic pain.

“Breakthrough” pain is another type of pain often identified by health care professionals who treat patients with SCD. This term literally means the act of breaking through pain relief. Originally used to describe patients with cancer pain who were maintained on a stable dose of analgesics, breakthrough pain was defined as a flair-up of sudden pain unresponsive to usual therapy. Such a flare-up is usually sudden and incidental, and can last from a few seconds to a few hours. There are currently no data that clearly describe or can be used to define breakthrough pain in SCD.

The pathophysiology, management, and goals of treating chronic pain differ from those related to acute pain. Whereas the aim of acute pain treatment is to heal the acute process, the aim of chronic pain management is to restore function and improve the quality of life. With the onset of chronic pain of unknown etiology, there seems to be a process of “rewiring” in the brain, where the threshold for pain perception is lowered so that ambient environmental stimuli that are normally painless or mildly painful induce the perception of severe pain. Chronic pain is often associated with other conditions that enhance its chronicity. These include psychosocial factors such as depression, anxiety, feelings of despair, insomnia, loneliness, helplessness, post­ traumatic stress disorder (PTSD), and dependence on pain medications.

Management of chronic pain in people with SCD is a major challenge for healthcare professionals. The goals of providing adequate pain relief to improve functionality and quality of life must be balanced by the need to minimize the risk of abuse, misuse, or diversion of opioids-medications which are a mainstay in managing chronic pain in people with SCD. Believing the patient’s report of pain is critical to optimizing therapeutic outcomes and achieving adequate pain relief and maintaining or improving functionality and the person’s quality of life.

Medications used to treat SCD-related pain should be tailored to the individual. Medications include nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antidepressants, and anticonvulsant medications. Management of all types of chronic pain associated with SCD may be enhanced by adding nonpharmacologic approaches. These may include psychological intervention, occupational therapy, behavioral and cognitive interventions, acupuncture, mild to moderate exercise if tolerable, and aqua therapy.

Key Question

Summary of the Evidence
To develop recommendations for the management of chronic pain in SCD, the methodology team conducted a comprehensive systematic review of studies that evaluated the efficacy and harms of different management approaches for chronic pain in SCD. Eight studies (two RCTs and six observational studies) and 13 case reports were eligible for inclusion.

One study explored general chronic sickle cell pain and compared utilization of massage therapy and progressive muscle relaxation to massage therapy alone and found no significant differences between the two approaches.301 The second study assessed hip pain and demonstrated a statistically significant difference between transcutaneous sodium salicylate iontophoresis and parenteral analgesics, favoring iontophoresis. The observational studies were fairly small and described various sickle cell-related pain presentations and management approaches. The baseline characteristics and outcomes of these studies are described in the evidence table.

In general, the quality of the available evidence was very low, so the expert panel determined that higher quality evidence with better precision should be derived from studies that evaluated chronic pain management in other settings. Such a body of evidence is larger and includes a wider scope of interventions and comparisons, which could lead to more useful recommendations for practitioners caring for people with SCD who have chronic pain. The panel and the methodology team appraised the quality of the guidelines for the management of chronic pain published by the American Pain Society in collaboration with the American Academy of Pain Medicine. The quality of the guidelines was deemed acceptable, so the panel adapted selected recommendations applicable to people with SCD as shown below in the “Recommendations” section, and these are labeled accordingly.

Recommendations
Determine the cause and type of SCD-related chronic pain. This includes chronic pain with objective signs such as avascular necrosis (AVN) and leg ulcers,and chronic pain without objective signs due to neuroplasticity of the peripheral or central nervous system.
(Consensus-Adapted)
Use a combination of the patient’s response to treatment-including pain relief, side effects,and functional outcomes-to guide the long-term use of opioids.
(Consensus-Adapted)
Encourage people to use deep tissue/deep pressure massage therapy,muscle relaxation therapy, and self-hypnosis as indicated.
(Weak Recommendation, Low-Quality Evidence)
Use long- and short-acting opioids to manage chronic pain that is not relieved by nonopioids. (Consensus-Adapted)

Assess all people with SCD for chronic pain annually or more often as needed. This assessment should include descriptors of the pain; its severity on a numerical scale; its location; factors that precipitate or relieve it, including biopsychosocial factors;and its effect on the patient’s mood,activity,employment, quality of life, and vital signs. (Consensus-Adapted)

Use a partnership agreement leading to a written, individualized treatment plan (to include risks, benefits, and side effects) with the patient if long-term opioids are indicated. The partnership agreement should list the patient’s rights and responsibilities, and the treatment plan should list the type, amount, and route of administration of the opioid in question,including random drug urine testing. (Consensus-Adapted)

Appoint one physician or other clinician to write the biweekly to monthly prescriptions for long-term opioids. Refills without seeing the patient should be kept to a minimum, and people on chronic opioid therapy must be evaluated in person every 2-3 months. (Consensus-Adapted)

Document all encounters with a patient, including medical history, physical exam, diagnosis, plan of management, type and amount of opioids prescribed and their side effects, if any, and lab data as needed. (Consensus-Adapted)

Encourage people receiving opioids to increase their fluid intake, maintain dietary fiber intake per the current dietary fiber recommendations, and to use stool softeners and bowel stimulant laxatives such as senna and/or docusate as needed. (Consensus-Adapted)

Believe the patient’s report of pain and optimize therapeutic outcomes to achieve adequate pain relief and improve the patient’s quality of life. (Consensus-Adapted)

Refer patients for evaluation by a mental health professional such as a psychiatrist, social worker, or addiction specialist as needed. (Consensus-Adapted)

Assess all people for other types of non-SCD related chronic pain including postoperative pain, pain due to trauma, pain due to therapy, iatrogenic pain, and pain due to comorbid conditions. (Consensus-Adapted)