Stories about: pain

Using ultrasound to trigger on-demand, site-specific pain relief

Ultrasound being applied to agitate injected liposomes, which then release nerve blocking medication that stops pain at the site
Ultrasound triggers the release of local anesthetics from injectable liposomes. Credit: Mary O’Reilly

According to the CDC, 91 people die from opioid overdoses every day in the U.S. Here in Massachusetts, the state has an opioid-related death rate that is more than twice the national average.

“Opioid abuse is a growing problem in healthcare,” says Daniel Kohane, MD, PhD, a senior associate in critical care medicine at Boston Children’s and professor of anesthesiology at Harvard Medical School.

Now, Kohane and other scientists who are developing triggerable drug delivery systems at Boston Children’s Hospital have found a new way to non-invasively relieve pain without opioids. Their novel system uses ultrasound to trigger the release of nerve-blocking agents — injected into specific sites of the body ahead of time — when and where pain relief is needed most. A paper describing the findings was published online today in Nature Biomedical Engineering.

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Precision drug delivery systems could ‘trigger’ an age of nanomedicine

Nanoscale drug delivery systems could target and destroy diseases in our body with increased precision and reduced side effects.

What if we could deliver biocompatible nanoparticles into the body and then activate them to release drugs exactly where they are needed, without causing side effects elsewhere?

Scientists like Daniel Kohane, MD, PhD, of Boston Children’s Hospital, are developing nanoscale drug delivery systems to do just that, using a variety of materials and triggers that are sensitive to a range of specific stimuli.

“Triggerable drug delivery systems could improve the treatment of many diseases by reducing side effects and increasing the effectiveness of therapeutics,” says Kohane, who directs the Laboratory for Biomaterials and Drug Delivery at Boston Children’s. He is the senior author on a recent article about the topic in Nature Reviews Materials.

One potential use of nanoscale drug delivery systems is of special interest to Kohane and his lab members

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To address chronic pain, you need to address sleep

chronic pain
Acute or chronic sleep loss exacerbates pain, finds a study that kept mice awake for long periods by entertaining them.

The ongoing opioid epidemic underscores the dire need for new pain medications that aren’t addicting. New research published today in Nature Medicine suggests a possible avenue of relief for people with chronic pain: simply getting more sleep, or, failing that, taking medications to promote wakefulness.

In an unusually rigorous mouse study, either approach relieved pain better than ibuprofen or even morphine. The findings reveal an unexpected role for alertness in setting pain sensitivity.

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Overcoming pain by tackling the fear factor

chronic regional pain syndrome
Grace Cahners prior to fear-based therapy (photos: Leigh Cahners)

When 11-year old Grace Cahners broke her foot in July 2015, she received the usual support boot, then casting and several weeks of physical therapy (PT). But instead of getting better, her pain intensified over the course of five months, forcing her to miss the first 54 days of sixth grade. She lost her normally sunny disposition and became crippled by fear.

Grace was diagnosed with complex regional pain syndrome (CRPS), a chronic pain condition in which the brain sends an over-abundance of pain signals to the affected limb. Not a newcomer to pain – Grace was diagnosed with psoriatic arthritis at the age of 13 months – she was using a wheelchair by December.

Leigh Cahners, Grace’s mother, knew that full-day narcotic pain medications and traditional PT would not restore Grace’s ability to walk. “I knew we needed another approach,” she says.

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DIY pain relief with light-activated local nerve blocks

light-activated liposomes
Injected, gold-coated liposomes could release painkillers on demand when heated with NIR light. (Shutterstock)

You’ve just had a root canal or knee surgery — both situations that will likely require some sort of local pain medication. But instead of taking a systemic narcotic with all its side effects, what if you could medicate only the part of your body that hurts, only when needed and only as much as necessary?

That concept is today’s reality in the laboratory of Daniel Kohane, MD, PhD, professor of anesthesia at Harvard Medical School and a senior associate in pediatric critical care at Boston Children’s Hospital.

The Kohane laboratory is developing a patient-triggered drug delivery system — but not a simple time-release mechanism or one tethered to ports or pumps. Instead, around the time of an intervention, pain medication would be injected into the site, or around a nerve leading to that site. Whenever pain relief is needed, the patient triggers release of the drug with a laser-like light-emitting device. “It’s like carrying the pharmacy in your body,” explains Kohane.

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A calmer rodent is a better rodent for pain medication research

The global market for pain medications is huge — some estimates predict it will hit $41.6 billion by 2017. However, the costs of pain medicine development are huge, too; it takes roughly $900 million to bring a new analgesic compound to market. In part, this is because some 80 percent of compounds that look promising in preclinical animal studies (largely in rodents) fail in late-stage clinical trials.

David Roberson, MBA, a neuroscience graduate student in the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, wants to make those preclinical studies better at predicting whether a new compound will work safely in people — by studying rodents at “home.”

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The diagnostic odyssey: Parents shed light on their experience

the diagnostic journey
Robert Salmon: Storm at sea (Wikimedia Commons)

Nikkola Carmichael, MS, CGC, is a parent and a genetic counselor in the adult genetics clinic at Brigham and Women’s Hospital. Her research was conducted as part of her master’s degree in genetic counseling in conjunction with colleagues at Boston Children’s Hospital.

When a parent or provider first becomes concerned about a child’s development, a diagnostic odyssey begins. It may be brief or can stretch for years as a child undergoes multiple procedures and medical appointments in the search for a diagnosis.

This is a challenging time for families. While learning to address their child’s health needs and fearing for the future, parents may have difficulty accessing support services due to the lack of a diagnosis. Against this backdrop of emotional turmoil, parents strive to support their child through medical procedures that can be painful or frightening.

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Putting a number on pain: A systems neuroscience approach

Wong-Baker pain faces subjective objective pain assessment systems neuroscience David Borsook
Subjective measures of pain, like the Wong-Baker face scale (above), are useful in assessing patients' pain, but objective measures would be far better.

“How much pain are you in?” It’s a harder question than you think. Tools for assessing patients’ pain—be they children or adults—rely on their perception: a subjective measure that eludes quantification and can change in response to any number of emotional, psychological or physiological factors.

Being able to objectively quantify pain could open the door to better pain management (especially for patients with chronic or neuropathic pain), better anesthetic dosing during surgical procedures, better understanding of addiction (and how to avoid it) and more.

To do so, we need measurable markers: physiologic parameters that reliably and quantitatively change during the experience of pain. But according to pain researcher David Borsook, MD, PhD—of Boston Children’s Hospital’s departments of Anesthesiology, Perioperative and Pain Medicine and Radiology—discovering such markers requires a better understanding of the larger context and of events that trigger pain, a perspective he refers to as “systems neuroscience.”

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Brain stimulation advances toward application in pediatrics

Rotenberg_AlexanderAlexander Rotenberg, MD, PhD, is a pediatric neurologist and epileptologist at Boston Children’s Hospital and director of the hospital’s Neuromodulation Program.

In recent years, electrical devices stimulating the brain or peripheral nerves have emerged as clinical and scientific tools in neurology and psychiatry. In 2014, the Food and Drug Administration has approved three tools at this writing: a device for treatment of epileptic seizures via electrodes implanted beneath the skull; a device for shortening migraine headache via transcranial magnetic stimulation (TMS) of the brain; and a transcutaneous electrical nerve stimulation (TENS) device for migraine prevention. (Click image below for details.)

Stimulating the nervous system to treat neuropsychiatric symptoms is not new. In the first century AD, the Roman physician Scribonius Largus documented treating headaches by applying electric torpedo fish to the head.

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Bacteria use pain as a weapon

It’s bad enough that invasive infections are painful. New work suggests that pain is only a means to an end for virulent bacteria: It’s how they suppress our immune system.

Staph found near fibers from pain neurons
Invasive methicillin-resistant Staphylococcus aureus (labeled by green fluorescent protein) are found close to pain nerve fibers (labeled by red fluorescent protein) in dermal skin tissue following infection

Previously, the pain from invasive infections like meningitis, necrotizing fasciitis, urinary tract infections, dental caries and intestinal infections was thought to be due to the body’s immune response, causing the infected tissue to become inflamed and swollen.

Not so, says Boston Children’s Hospital neuro-immunologist Isaac Chiu, PhD. Studying invasive skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in live mice, his team’s research demonstrates that the pain is induced by the bacteria themselves, and kicks in well before tissue swelling peaks.

Adding outrage to insult, once the pain-sensing neurons are activated, they suppress the immune system, potentially allowing the bacteria to proliferate, finds the study, published last week in Nature.

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