Can rare pain syndromes point the way to new analgesics?

analgesic drug discovery could reduce prescription opioid use
Boston Children’s Hospital and Amgen will collaborate to discover and accelerate non-addicting pain drugs.

As the opioid epidemic deepens and drug overdoses increase, effective non-addicting painkillers are desperately needed. Efforts to discover new pain pathways to target with new drugs have thus far had little success. Other promising research is investigating triggerable local delivery systems for non-opioid nerve blockers, but it’s still in the early stages.

A new collaboration between Boston Children’s Hospital and the biopharmaceutical company Amgen is aimed at accelerating new pain treatments. Announced yesterday, it will revolve around patients with rare, perplexing pain syndromes. The scientists hope that the genetic variants they find in these patients will shed new light on pain biology and lead to new ways of controlling pain. 

“Traditional approaches to analgesic drug discovery have been pretty disappointing over the past 20 years,” says Charles Berde, MD, PhD, chief of the Division of Pain Medicine in Boston Children’s Department of Anesthesiology, Perioperative and Pain Medicine. “Patients with unusual patterns of increased or decreased pain responsiveness can offer important clues in this pursuit.”

From rare pain syndromes to the common

Berde is one of the three lead Boston Children’s researchers under the agreement, together with Michael Costigan, PhD, of the F.M. Kirby Neurobiology Center and the Department of Anesthesiology, Perioperative and Pain Medicine, and Catherine Brownstein, MPH, PhD, in the Division of Genetics and Genomics and scientific director of the Manton Center for Orphan Disease Research.

Boston Children’s Division of Pain Medicine is a magnet for patients around the world. Its clinicians see patients with rare conditions that make them strikingly insensitive to pain or, conversely, hypersensitive to pain or apt to experience pain with no apparent stimulus. Through the Manton Center, patients and families can receive genetic counseling and submit samples for genetic studies including whole exome, whole genome and RNA sequencing.

The one-year collaboration with Amgen will explore the genetics of such conditions as:

  • paroxysmal extreme pain disorder, characterized by skin flushing and severe pain attacks in the rectal, jaw and eye areas
  • erythromelalgia, a condition causing intense, burning pain in the extremities (“literally, your foot, is on top of a flame… that you can’t put out,” says one sufferer)
  • hereditary sensory and autonomic neuropathy (HSAN), a family of disorders involving decreased pain sensitivity
  • chronic pain associated with infantile ascending hereditary spastic paralysis

“Rare pain conditions provide an extraordinary opportunity for discovery of new pain mechanisms and new targets for potential painkillers,” says Brownstein. “These might also apply to more common forms of pain.”

Modeling pain

Brownstein, Berde and Costigan have already identified new gene mutations related to pain. With Amgen’s scientists, they plan to further explore some of these in animal models such as zebrafish and in neurons made from patients’ own cells. Advanced bioinformatics techniques will help uncover and analyze potential pharmaceutical targets.

“By looking at pain-related genes that are conserved across different species, we hope to identify the strongest genetic targets and subsequently work up the very best ways of curbing chronic pain,” says Costigan, who has worked in pain genetics for more than two decades. “The more patients we evaluate, the stronger our chances of finding novel effective medicines.”

John Dunlop, PhD, Amgen’s vice president of Neuroscience Research, agrees.

“Amgen is pleased to enter into this collaboration as it underscores our extensive investment and expertise in pursuing targets that have clear genetic support,” he says.

Patients/families interested in enrolling in this study should email the Manton Center at gdc@childrens.harvard.edu.