NCCIH aims to close knowledge gaps, add integrative therapies for sickle cell pain

Photo Cred: Ousa Chea/Unsplash

By Judy Packer-Tursman

The National Center for Complementary and Integrative Health (NCCIH) posted a notice of special interest December 20 for “high priority pain research,” with pain related to sickle cell disease topping the list. Clinician experts in the field anticipate expanding integrative therapy options for pain, which will help better manage the blood disorder after decades of scant research due to a paucity of federal money and interest.

While a “notice of special interest” is not a funding opportunity announcement per se, it serves a similar purpose by attracting investigators to particular areas of science where NIH has identified gaps in knowledge and an unmet need for research.

“I think it is promising,” said Carlton Dampier, MD, a national expert on sickle cell disease who has studied and used integrative as well as mainstream therapies over the span of four decades. “There was a good 20 to 25 years in the mid-1990s, early 2000s where there was almost no funding available at all.”

Over the past five to 10 years, drug manufacturers spurred on by financial incentives have been working to develop therapies for sickle cell and other orphan diseases, said Dampier, professor of pediatrics at Emory University School of Medicine in Atlanta. Biotech companies are making inroads into gene therapy aimed at alleviating severe pain crises commonly experienced by sickle cell patients and potentially finding a cure.

Still, few medications are currently available to manage the debilitating condition. As researchers said in a 2019 article in Current Opinion in Hematology: “Pain is a major comorbidity of sickle cell disease. Opioids are the mainstay for pain treatment but remain suboptimal.” 

In fact, the biological causes of pain in people with sickle cell disease, a group of blood disorders including sickle cell anemia, are poorly understood and “significant gaps” remain in translating research into effective treatment strategies, NCCIH said.

“It’s been “110 years since [sickle cell disease] was discovered, and until 2019 we had only one drug approved for it,” said Rabi Hanna, MD, chair of Cleveland Clinic’s department of pediatric hematology/oncology. “Hopefully, with the funding, [researchers will find] creative ideas to combine different therapies and to try new ones.”

Sickle cell disease affects 20 million-plus people globally, including about 100,000 individuals in the United States, mostly of African descent and roughly half of whom are children. Pain is the most common complication of the inherited illness, NCCIH noted.

NCCIH will consider applications ranging from basic research to clinical trials, exploring “fundamental processes” in sickle cell pain as well as “potential treatments with a variety of therapies including complementary and integrative health approaches.” The broad language is intentional; no specific therapies are named because, as one NCCIH official said, “We don’t want to dictate. It all depends on which approach is ready.”

Given the “remarkable complexity” of sickle cell disease, Dampier sees a future in which pharmacological and integrative therapies are used in combination. Despite the hope that advances in gene therapy ultimately will cure the illness, he said, “I think we’ll always have some individuals with breakthrough pain who will need [drugs] and complementary therapies.”

Hanna agrees, describing sickle cell as a systemic disease that, like cancer, requires “multiple approaches” and “full psycho-social support” for its management. Cleveland Clinic is conducting a gene therapy study, he said, but access to such treatment could be difficult.

Hanna’s approach includes using Endari (L-glutamine oral powder), acupressure, virtual reality, and music therapy to help with pain management.

Dampier has been involved in studies of hypnosis, physical therapies including massage and therapeutic touch, and acupuncture for sickle cell patients. “All of [these therapies] seem to be helpful to some degree,” he said, but information is lacking on which therapy might work best for a specific symptom or complication in a particular individual.

It’s even more challenging because complementary therapies are often poorly reimbursed by private insurers, Medicare and Medicaid, and “not particularly available in the inner cities where these [sickle cell] patients live,” Dampier said.

Cognitive behavioral therapy is known to be “quite effective” for sickle cell patients, but typically requires an experienced psychologist working one-on-one with the patient, Dampier said. “So, a number of us are looking at how we might deliver such therapies over the internet or with apps to reach a wider audience with more treatment options.”

Inna Belfer, MD, PhD, program director for basic and mechanistic research in NCCIH’s Division of Extramural Research, said researchers might decide to start at the beginning in investigating complementary therapies for sickle cell pain instead of building upon previous studies.

Belfer said NCCIH’s inclusion of sickle cell disease in high priority pain research sprang from an NIH workshop in 2021, and NIH’s HEAL (Helping to End Addiction Long-term) initiative launched in 2018 to address the national opioid crisis. HEAL expects to commit $1.5 million in direct costs in fiscal year 2022 to fund approximately three awards. 

Opioids must continue to be an option for sudden sickle-cell pain crises that “can happen at any time, in any organ, in any tissue,” Belfer said. But more treatment options are needed, “and we know that many complementary approaches are successful in pediatric populations.”

Editor’s note: This article was updated on January 20, 2022. The National Center for Complementary and Integrative Health was incorrectly attributed as the National Institutes of Health.