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17 Articles in Volume 20, Issue #1
20/20 with Lynn Webster, MD
Analgesics of the Future: Peripheral Kappa Opioid Receptor Agonists
Correspondence: Opioid-Induced Hyperalgesia; Pain Care in Older Adults
Don’t Discount the Role of Diet for Chronic Pain Relief
Editorial: Why Haven’t There Been More Breakthrough Analgesics?
Gasping for Air: Sleep-Disordered Breathing and Chronic Opioids
How can botulinum toxin be used in chronic pain syndromes?
Neurodestructive Interventions for Cancer Pain
Obesity and Pain Care: Multifaceted Considerations for Treatment
Obesity and Rheumatoid Arthritis: What Clinicians Should Know
Sickle Cell Pain Crisis: Clinical Guidelines for the Use of Oxygen
The Complexity of Sickle Cell Pain: An Overview
The Perseverance Loop: The Psychology of Pain and Factors in Pain Perception
The Rapid Rise of Non-Opioid Pain Policies
Treating Pain by Overcoming Communication Barriers
Visual Artists Tackle What Pain Looks Like
Will 2020 Be the Year of Patient Education?

The Complexity of Sickle Cell Pain: An Overview

Is sickle cell disease nociceptive or neuropathic? Perhaps neither.

with Susanna Curtis, MD

Sickle cell disease is a complex inherited disorder of the red blood cells that causes episodic and often chronic pain. The good news is that childhood deaths related to sickle cell disease (SCD) are falling. The bad news is that research has shown a slight uptick in mortality for adult SCD patients. The culprit may be treatment: according to the Sickle Cell Disease Coalition, 75% of adults with SCD are not getting appropriate care for pain related to the disease.1-3

Patients with SCD tend to transition from experiencing episodic pain to persistent pain, resulting in more than half of adult SCD patients living with chronic pain. Chronic pain in SCD has been associated with poor patient-reported outcomes, including anxiety, depression, fatigue, and the inability to function. Individuals with SCD are less likely to have access to comprehensive care than those with genetic disorders such as cystic fibrosis or hemophilia.3,4

The situation has improved somewhat in recent years, thanks in part to updated treatment guidelines from the NIH.5 In addition, the American Society of Hematology (ASH) is working on guidelines for the management of acute and chronic pain associated with SCD; these recommendations are expected to be released soon.6

Still, treating SCD pain is an ongoing challenge. Only four medications are available and indicated for the treatment of the disease, and none of them target pain. Current treatment options simply do not reflect SCD's complexity. This past year, researchers from the Yale Cancer Center (YCC) in New Haven set out to change that by shedding some light on the types of pain that present with SCD. By more fully understanding the pain type, treatment for sickle cell disease may improve.

According to the CDC, sickle cell disease (SCD) affects an estimated 100,000 Americans, including one in 365 African Americans, and one in 16,300 Hispanic Americans. (Image: iStock)

SCD Pain: Neuropathic or Nociceptive?

Pain in patients with SCD has generally been considered primarily nociceptive. “[The] pain often has been thought of as coming and going,” explained Susanna Curtis, MD, a post-doctoral fellow at YCC and lead author of the YCC study, which she presented at the ASH 2019 annual meeting in Orlando.7 “Tissue dies, causing pain, then is repaired and the pain improves. But some patients have pain every day, even when there is no tissue damage.” Recent research has shown that indivdiuals with SCD can also have neuropathic pain. However, added Dr. Curtis, these studies “did not look at how neuropathic pain intersected with other types of pain. We wanted to try to sort out the types of pain.”

Dr. Curtis and her team divided adult SCD patients who receive care in the Adult Sickle Cell program at Yale New Haven Hospital into two groups. One group reported above-average levels of regular baseline pain. The second group reported below-average regular baseline pain. Levels were assessed using the Adult Sickle Cell Quality of Life Information System (ASCQ-ME) scale while levels of neuropathic pain were measured by a validated pain scale not specific to SCD. The ASCQ-ME pain episode frequency and severity domains referenced the previous 12 months, social impact the previous 30 days, and other domains the previous 7 days.

The group with the least reported pain had no neuropathic pain. Of those with the worst pain, about half reported neuropathic pain. “All patients with neuropathic pain had nociceptive pain as well,” Dr. Curtis noted, and “none of the patients had only neuropathic pain.”

The results indicated that chronic pain in SCD is likely due to a variety of pathologies, including neurological dysfunction. “We know that both peripheral and central sensitivity occurs in SCD. But it’s hard to show exactly what’s going on,” said Dr. Curtis. “We can’t prove with this study that central sensitization is causing pain in SCD, but it’s worth looking at in future studies.”

Emotional Components

It’s also important to note that participating patients with neuropathic pain also reported more anxiety and sleep difficulties. Dr. Curtis reinforced that, “with pain, the emotional component is important—memories of pain, how pain affects daily life, and so on…. People with central sensitization have more depression and anxiety. And anxiety makes pain worse.” This creates a feedback loop than can be difficult to break. Frequent hospitalization and other factors can also add to the burden of the disease, whether SCD or another chronic pain condition.

Overall, said Dr. Curtis, “If we can show what’s causing the pain, it will be easier to make treatment decisions. If a patient has signs of neuropathic pain, don’t let the fact that the patient is being treated for nociceptive pain stop you from using treatments for neuropathic pain as well.” She also stressed the importance of ensuring that patients’ mental health issues are being addressed as, like many chronic pain conditions, “SCD is really a biopsychosocial disease.”

Last updated on: June 18, 2020
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Sickle Cell Pain Crisis: Clinical Guidelines for the Use of Oxygen
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