Consider this scenario: A patient is home recovering from knee surgery to repair an ACL tear. Her pain medications are wearing off, and the surgical cuts are starting to throb. Reaching over to the table she picks up what’s essentially a souped-up laser pointer, points it at the surgical wound and turns it on. Within seconds, the pain starts to fade.
This picture isn’t as far-fetched as you might think. In a pair of simultaneous papers, Boston Children’s Hospital’s Daniel Kohane, MD, PhD, and his laboratory recently reported their efforts to create not one, but two methods for packaging long-lasting local anesthetics in microspheres that could be injected in advance by a surgeon or anesthesiologist and that would release the drugs when zapped with a laser. Both methods have one goal in common: to provide patients with durable, localized and personalized control of surgical, traumatic or chronic pain with minimal side effects.
“Current approaches to postoperative pain rely on systemic analgesics, especially narcotics, which come with side effects and risks of tolerance, addition and diversion,” said Kohane, a physician in Boston Children’s Department of Critical Care Medicine. “While there is extensive literature on targeted drug delivery, the technologies developed to date are either on or off; they cannot be adjusted or repeatedly triggered to provide a desired, durable level of analgesia.
“Our goal,” he continued, “was to engineer an approach to pain control that once administered could be triggered as needed.”
In one paper, published in the Proceedings of the National Academy of Sciences, Alina Rwei, a graduate student in Kohane’s lab and in the MIT Department of Materials Science and Engineering, showed that she could block pain signals from rats’ hindpaws by injecting microspheres loaded with tetrodotoxin (a potent local anesthetic) into the animals’ sciatic nerve. When struck with near-infrared (NIR) light, a photosensitizing agent in the microspheres produces reactive oxygen molecules, making the spheres porous and letting tetrodotoxin out.
In the second paper, in Nano Letters, Kohane lab postdoc Changyou Zhan, PhD, demonstrated a similar effect using gold nanorod-embedded microspheres injected into rats’ foodpads. Loaded with tetrodotoxin and dexmedetomidine (which prolongs tetrodotoxin’s effects), Zhan’s microspheres become porous when NIR light heats the nanorods.
In both systems, the lab showed they could tune the intensity and duration of pain blockade by varying the intensity of the laser beam and how frequently and for how long the microspheres were exposed. Rwei, for instance, could repeatedly trigger drug release from her microspheres for up to two days, and Zhan for up to five.
According to Kohane, both technologies represent major steps in addressing unmet medical needs for patient-adjustable local pain relief.
“If we can translate these technologies to patients, it could change dramatically the way we approach postoperative pain care by providing pain relief that doesn’t involve narcotic agents and which doesn’t have to fade away within a few hours,” he said. “And in my mind, pain is the low-hanging fruit. There are many clinical situations and applications where repeated, modulated, on-demand drug release would be desirable.”