Chiropractic + Naturopathic Doctor • July August 2016 • Roundup

The National Pain Strategy, released this year by the U. S. Department of Health and Human Services, places strong emphasis on self management and patient education as critical pathways for improving treatment of chronic pain, especially back pain.

At the recent American Pain Society’s (APS) Annual Scientific Meeting, researchers representing the Veterans Affairs (VA) and North American Spine Foundation discussed implications of the National Pain Strategy for improving pain management and reducing disability.

The VA estimated in one study that 44 per cent of soldiers in an Army infantry brigade reported chronic pain three months after returning from tours of duty in Afghanistan and Iraq – double the rate among civilians. The North American Spine Foundation says spinal disorders have increased by 300 per cent in the last 50 years and now rank as the number-one cause of disability in the United States and in the military.

Robert Kerns, professor of psychiatry, neurology and psychology at Yale University, spent 38 years practicing in VA health care. He reported in a panel presentation at the APS meeting that the VA’s stepped-care model to help veterans better manage pain through standardized pain assessments, alternative therapies, patient education and selfcare is succeeding in reducing opioids use.

“The proportion of VA patients receiving high doses of opioids has decreased significantly in the last four years concurrent with greater use of non drug alternative pain therapies,” Kerns said.

He cited better self-management and patient education as examples of new ways the VA is working to improve pain care for veterans, and believes the National Pain Strategy’s strong advocacy of self-care will provide more educational resources and greater incentives to help physicians empower patients to become more proficient at managing and coping with their pain.

In his panel presentation, Michael Reed, executive director, North American Spine Foundation, addressed the importance of emphasizing function to prevent or minimize disability in people with spinal disorders.

“The current treatment paradigm addresses pain first and function second, but it should be reversed,” said Reed. “The pendulum may have swung too far forward in addressing pain and not function, so we need to emphasize both in balance.”

Reed reported that the financial impact – direct medical costs, disability payments, lost work time costs and patient costs – associated with spinal disorders currently are estimated at more than $600 billion a year in the United States alone and Social Security disability payments are approximately $40 billion.

A new study in zebrafish suggests that irregular fluid flow through the spinal column brought on by gene mutations is linked to a type of scoliosis that can affect humans during adolescence. Found in humans and zebra fish, these mutated genes damage the cilia – tiny hairlike projections that line the spinal canal and help move the fluid – and lead to a curvature of the spine.

Researchers from Princeton University and the University of Toronto found that when they repaired the mutated cilia genes, they restored cerebrospinal fluid flow and could prevent spinal curves from developing. If translatable to humans, the study could lead to a non-surgical approach for treating the condition known as idiopathic scoliosis, which has no known cause and affects roughly three out of every 100 adolescents. The research was published June 10 by the journal Science.

“This is the first hint of a biological mechanism for idiopathic scoliosis,” said Rebecca Burdine, associate professor of molecular biology at Princeton, and a senior author of the study. “We hope this research will open up new areas of inquiry as to how the disruptions to normal cerebrospinal fluid flow can lead to spinal curvature.”

Burdine’s lab conducted the study in collaboration with a team led by senior author Brian Ciruna, an associate professor of molecular genetics at the University of Toronto and a senior scientist at the Hospital for Sick Children in Toronto.

“Traditionally, theories regarding the biology behind idiopathic scoliosis have revolved around defects in the bone, cartilage or neuromuscular activity,” Ciruna said. “The finding that defects in cerebrospinal fluid flow may be contributing to scoliosis came as a surprise. It is not a theory that had been put out there previously.”

The study is the first to link spinal curvature to mutations in genes that govern motile cilia, which stick out from cells and make synchronous whip-like motions to push fluid through narrow passages such as the spinal column.

Hazel Sive, a professor in biology at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology, who was not involved in this research, said the study is an important step toward understanding events underlying spinal curvature.

“In an elegant set of experiments, the authors take advantage of the outstanding zebrafish system to define that cilia function and perhaps cerebrospinal fluid flow is required for normal spinal cord development,” said Sive, who is an expert in the use of zebrafish to study vertebrate development.

Researchers in the Burdine laboratory had observed that mutant genes that disrupt cilia motility produce spinal curves in zebra fish as adults, although the work had not been published. “I’ve presented this finding for years, but didn’t have a way to link this work to human disease,” Burdine said. “Collaborating with Brian’s group helped us make this link.”

Previous research by Ciruna’s lab revealed that mutations in a gene found in zebra fish and humans called protein tyro sine kinase-7 (ptk7) causes spinal curvature during a period of rapid growth that corresponds to adolescence in zebra fish. Published in the journal Nature Communications in 2014, the findings suggested that the mutant fish could serve as a model for studying the condition. The researchers knew that the ptk7 gene plays a role in helping cells orient in the correct direction during embryonic development, but they didn’t know that it also governed the formation of motile cilia.

To explore how ptk7 mutations lead to spine curvature in zebra fish, Curtis Boswell, a graduate student at the University of Toronto, examined the brains and spinal cords of fish with mutated ptk7. In brain regions known as ventricles, which sit at the top of the spinal cord, the motile cilia were sparse and malformed and the fish developed a brain-swelling condition called hydrocephalus, which is associated with loss of cilia function. Using fluorescent dyes to track the flow of cerebrospinal fluid through the ventricles, the researchers saw that the flow was irregular and slower than normal.

When the researchers introduced a non-mutated version of the ptk7 gene specifically into tissues harboring motile cilia, the hydrocephalus disappeared, the cerebrospinal fluid began to flow normally and the spine straightened.

“We demonstrated that if we could restore gene function in the motile ciliated tissues, we could restore cerebrospinal fluid flow, and we could actually prevent scoliosis in these mutants,” Ciruna said.