Pain Management - OHSU News

Bridging the gap between immunology, wound care, dermatology to tackle rare diseases

Angela Yeager — Thu, 08 May 2025 14:55:00 GMT

Alex Ortega Loayza, M.D., M.C.R., interim chair and associate professor of dermatology at Oregon Health & Science University, has made significant strides in studying rare dermatological conditions, including pioneering work on pyoderma gangrenosum. (OHSU/Christine Torres Hicks)

Alex Ortega Loayza, M.D., M.C.R., interim chair and associate professor of dermatology at Oregon Health & Science University, has made significant strides in studying rare dermatological conditions, including pioneering work on pyoderma gangrenosum — a rare and often misdiagnosed chronic skin disorder that causes deep, painful ulcers -- that has made him a leader worldwide on this debilitating disease.

Alex Ortega Loayza, M.D., M.C.R. (OHSU)

Originally from Peru, his journey into the world of dermatology and immunology was shaped by his personal experiences, the mentorship he received and his drive to address the challenges faced by patients suffering from rare skin diseases.

From Peru to the U.S. — a focus on rare dermatological diseases

Ortega’s passion for dermatology was sparked during medical school in Peru, where he studied endemic pemphigus foliaceus — the only known autoimmune disease that is also endemic — characterized by painful blisters, especially common in people living in the jungle.

“I saw people ostracized and isolated because they thought they were contagious,” he said.

This disease, which causes patients to feel as though they are "on fire" due to the burning sensation caused by skin lesions, inspired his drive to understand the disease and find ways to improve the lives of those affected.

One of his mentors from Peru and chair emeritus of University of North Carolina Dermatology, Luis Diaz, M.D., a prominent figure in the study of endemic pemphigus, introduced him to leading-edge research on rare skin diseases.

“Diaz gave me the opportunity to expand my research and really think about how these rare diseases affect people,” Ortega said.

Building foundations in dermatology and immunology

Ortega’s path took him to Virginia Commonwealth University, where he pursued a combined residency in internal medicine and dermatology. During his time there, with mentorship from another dermatologist, Julia Nunley, M.D., he began to delve into the complexities of diseases that involved both the immune system and the skin. One condition that stood out to him was pyoderma gangrenosum, or PG. There is not a cure, or even an approved drug therapy, for PG.

“I started seeing these patients with large skin ulcers and I wanted to understand why this was happening,” Ortega said. “I asked myself, ‘Why do we not have better answers?’”

After collaborating with basic scientists specializing in neutrophil biology, the study of a type of white blood cells, and immunology, he co-authored a pivotal review paper in 2015 that would become foundational in PG research.

“That was my first paper as a faculty member,” he said. “It’s been cited over 300 times, and it helped me understand the development of PG.”

In addition to the intellectual challenge, PG offered a unique intersection of immunology, wound care and dermatology — fields that are often studied separately, despite their close connection in conditions like PG.

“The way your immune system can cause ulcers like that was striking to me,” he said “It was a perfect intersection of all these three fields. And it led me to really dive deeper into the mechanisms behind PG,” he explained.

Overcoming diagnostic challenges

Ortega came to OHSU in 2016 after meeting Nicole Fett, M.D., an OHSU dermatologist who specializes in autoimmune disorders. He wanted a place where he could grow his research on PG and other rare skin diseases and continue his clinical work. At OHSU, he assembled a team of basic scientists, biostatisticians and clinicians to form the pyoderma gangrenosum study team, or PYGAS.

One of the main challenges Ortega and his colleagues face in treating PG is the lack of a definitive diagnostic test. While other rare diseases, like pemphigus vulgaris, can be identified through immunological tests and skin biopsies, PG lacks specific markers.

“For PG, the skin biopsy is nonspecific,” Ortega said. “There is no objective test that can definitively tell us if a patient has PG. This has been a significant hurdle in both diagnosing and researching the condition.”

To address this issue, Ortega’s team has started experimenting with high-frequency ultrasound and other forms of imaging.

“We’ve begun using high-frequency ultrasound to visualize PG when it’s active and differentiate it from other conditions like skin cancer,” he said. “It’s a noninvasive, point-of-care testing method that might help clinicians diagnose PG more accurately in the future.”

Ortega is not only focused on understanding PG but also on developing effective treatments. Despite its devastating impact, there are currently no FDA-approved medications for PG.

“I feel fortunate to be part of two steering committees of clinical trials that are leading us toward FDA-approved medications in the next few years,” he said, adding that he is involved in two groundbreaking phase 3 clinical trials: one testing a complement 5a inhibitor and the other an interleukin 36 inhibitor, both of which target the immune system’s response to PG.

His dedication to improving treatments led him to become an NIH-funded investigator and co-founder of the Pyoderma Gangrenosum Group for the CHORD COUSIN Collaboration, a global research organization focused on advancing outcome measurements for skin conditions. He has been sponsored by the Medical Dermatology Society and American Academy of Dermatology to develop consensus guidelines to treat PG patients.

“Five years ago, there were no standardized ways to measure success in PG treatment,” he said. “Now, with this international group, we’re developing clear outcome measures that can guide industry investment in PG treatments.”

A holistic approach to healing

For Ortega, being a physician is not just about treating the physical symptoms of a disease; it’s also about offering emotional and psychological support to his patients. He has patients who travel from as far away as Alaska and Georgia for diagnosis and treatment. Patients who end up in his clinic often have been misdiagnosed multiple times and have ended up in the emergency room or urgent care.

“I see these patients who have been suffering, sometimes for years, and I know that I am often the last stop for them,” he said. “It’s not just about the physical healing; it’s also about providing hope that they can heal, and that they are not alone in their journey.”

He takes a holistic approach to patient care, wound care and pain management, often addressing mental health, nutrition and well-being alongside medical treatment.

“When I treat my patients, I try to understand the person as a whole," he said. "Physical healing is important but so is helping them find peace and hope in their journey.”

Ortega is focused on advancing his research and continuing to improve the lives of his patients. With his involvement in international collaborations, clinical trials and groundbreaking research, he is making lasting contributions to the fields of dermatology, wound care and immunology. His hope is that diseases such as PG will not be as widely misdiagnosed in the future, and there will be effective treatment options soon.

“I’ve been lucky to have supportive mentors, collaborators, team members and my own family who have stood by me through this journey,” he said. “We’ve been able to make real progress for patients suffering from rare diseases, and we will continue to push for better treatments, better diagnoses, and better care."

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Prestigious award seeks to advance new avenue of addiction treatment

Erik Robinson — Wed, 25 Sep 2024 14:46:00 GMT

James Frank, Ph.D., will use new Avenir Award funding from NIDA to investigate cannabinoid receptors as an alternative toward treatment for opioid use disorder. (OHSU/Christine Torres Hicks)

A chemical biologist at Oregon Health & Science University has become just the second researcher in the institution’s history to receive a prestigious Avenir Award from the National Institute on Drug Abuse, known as NIDA, of the National Institutes of Health.

James Frank, Ph.D. (OHSU)

James Frank, Ph.D., assistant professor of chemical physiology and biochemistry in the OHSU School of Medicine and the Vollum Institute at OHSU, will use the award to develop new tools to improve understanding of an alternative suite of receptors in the brain believed to be involved in opioid addiction. Existing medications to treat opioid use disorder target the brain’s opioid receptors, yet the recent surge of fentanyl into the illicit drug supply has supercharged an opioid epidemic that now kills 80,000 Americans annually. Fentanyl is 100 times more potent than morphine, which makes existing medications to treat addiction less effective.

“Because fentanyl is so potent and sticks to its receptors so effectively, the opioid-targeting drugs that we have in our toolkit don’t work as well,” he said. “So, we’re trying to develop new therapies that act on receptors outside of the opiate system.”

Using chemical tools developed in his OHSU lab, Frank’s research will focus on an alternative suite of receptors, called cannabinoid receptors, that are involved in the functions of pain management and addiction in the brain. Specifically, he will target a cannabinoid receptor known as CB2, as well as other orphan cannabinoid receptors like GPR55 that haven’t been as intensively studied as the CB1 cannabinoid receptor.

All are part of the nervous system’s endocannabinoid system, which is most notably associated with the use of cannabis.

“There are many parallels between the opioid and cannabinoid systems, in terms of where they’re expressed in the brain’s reward circuits, as well as how they act on those cells once activated,” Frank said. “We think that if we can better understand specific cannabinoid receptors and in which specific brain pathways they become activated in addiction, it may be possible to design new drugs to treat substance use disorders.”

Further, unlike opioid receptors, Frank says, cannabinoid receptors do not induce respiratory depression that can lead to death:“They have a higher safety profile compared with the opioid drugs that are currently available.”

The lab is developing new chemical tools capable of activating cannabinoid receptors on specific brain circuits with light. Combined with the use of fluorescent dyes, the Frank lab will discern — with detailed time and space specificity — how the introduction of opioids to cells within a Petri dish and in live mice changes the expression of cannabinoid receptors.

By using these state-of-the-art chemical tools, the goal of the research is to illuminate signaling mechanisms that could be useful in drug development.

Frank joined OHSU in 2018 as a research assistant professor in the Vollum Institute, with support from the Vollum Fellowship. He was promoted in 2021 to assistant professor in the School of Medicine.

The award provides $2.1 million over five years. The Avenir Awards support early-career investigators proposing new areas of research for the genetics or epigenetics of addiction.

Frank’s project was one of just two Avenir Awards in Chemistry and Pharmacology Research granted this year. NIDA has three Avenir award programs: research in HIV, genetics and epigenetics of substance use, and chemistry and pharmacology of substance use. Only two OHSU scientists have received an Avenir in any category.

Jamie Lo, M.D., M.C.R. (OHSU)

Jamie Lo, M.D., an associate professor of obstetrics and gynecology, was the first OHSU School of Medicine researcher to be awarded the prestigious grant: Lo received the Avenir Award in Genetics and Epigenetics in 2022 to develop research exploring how parents’ behavior and environment affects their offspring before birth, and, in some cases, before conception.

Frank’s award number is 1DP1DA060496-01 through the National Institute on Drug Abuse of the NIH.

All research involving animal subjects at OHSU must be reviewed and approved by the university’s Institutional Animal Care and Use Committee (IACUC). The IACUC’s priority is to ensure the health and safety of animal research subjects. The IACUC also reviews procedures to ensure the health and safety of the people who work with the animals. The IACUC conducts a rigorous review of all animal research proposals to ensure they demonstrate scientific value and justify the use of live animals.

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Amid opioid epidemic, training helps dentists safely manage patient pain

Franny White — Thu, 03 Nov 2022 14:50:00 GMT

OHSU dental resident Gianncarlo Cruz, D.D.S., demonstrates how dental professionals discuss safe pain management with patients on Tuesday, Nov. 1, 2022, at the OHSU School of Dentistry in Portland. (OHSU/Christine Torres Hicks)

Knowing the removal of wisdom teeth and other dental surgeries can involve powerful prescription painkillers, Oregon Health & Science University is helping dental professionals take steps to be responsible prescribers — an important effort in addressing the national opioid epidemic.

Richie Kohli, B.D.S., M.S. (OHSU)

“Because many who misuse opioids obtain prescription pills from family and friends, it’s important for dentists to discuss with patients how to securely store opioids and how to dispose of them when they’re no longer needed,” said Richie Kohli, B.D.S., M.S., associate professor in the OHSU School of Dentistry’s Division of Dental Public Health.

Since 2019, OHSU School of Dentistry faculty have organized 10 iterations of an interactive, web-based training series called Pain Management and Substance Abuse Disorder in Dental Settings. The training aims to help dentists, dental hygienists and others involved in oral health care to better understand the complex issues associated with substance use disorder and how the dental field can help address it.

Karan Replogle, D.D.S., M.S. (OHSU)

“Our goal is to help dentists be respectful prescribers who are informed of best practices,” said Karan Replogle, D.D.S., M.S., senior associate dean for clinical systems in the OHSU School of Dentistry. “For example, over-the-counter medications such as ibuprofen, acetaminophen or a combination of the two can relieve most dental pain more effectively than opioids. When opioids are recommended for severe pain, they’re rarely needed for more than three days.”

According to the National Institute of Dental and Craniofacial Research, about 75% of opioid abusers are believed to have been introduced to the drug through a prescription. In 2012, more than half of 14- to 17-year-olds received opioid prescriptions from dentists following wisdom tooth extractions. Dentists were the third-most-frequent prescribers of opioid pain medications in 2010.

After the U.S. government declared a public health emergency related to the nation’s opioid epidemic in 2017, awareness of potential opioid prescription abuse grew, and dentists began changing how they manage their patients’ pain. The OHSU School of Dentistry training seeks to help oral health care professionals do just that.

Replogle and Kohli are the lead organizers of the training series, which has been funded by the Oregon Health Authority and the U.S. Substance Abuse and Mental Health Services Administration. To date, 388 people involved in dental care — from 40 U.S. states and two Canadian provinces — have participated.

Over the course of seven weeks, the virtual series covers a variety of topics:

Helping patients understand what level of pain to expect before beginning a procedure.
When less-addictive painkillers, such as acetaminophen or non-steroidal anti-inflammatories, are effective for pain management.
What current research and guidelines recommend, and what state and federal laws require, for opioid prescriptions.
How dentists should use their state’s Prescription Drug Monitoring Program to check how frequently their patients have received opioid prescriptions from other providers.
What substance use disorder is and how to identify it in patients.
How dentists can help patients with substance use disorder manage pain in collaboration with their health care providers.
How unconscious biases can affect prescribing and other pain management practices.

In September, OHSU School of Dentistry faculty published a paper in the journal BMC Oral Health that showed the training is improving participants’ understanding of pain medications, substance use disorder, state Prescription Drug Monitoring Programs and more.

Held in collaboration with the Oregon ECHO Network at OHSU, the virtual, live video training uses the ECHO model, which features a mix of presentations by experts and discussions among participants about how to apply the information they’re learning to real-world examples in dental clinics. While this effective educational approach has been used for medicine for years, this series is believed to be the first time ECHO has been used for dentistry.

Training facilitators have included dental experts, addiction and emergency medicine physicians, a pharmacist, a social worker and a patient in recovery from substance use disorder. In addition to Replogle and Kohli, other OHSU faculty involved in the training series include: Barry Taylor, D.M.D. FAGD; Harjit Sehgal, B.D.S., M.S.; Brandon Maughan, M.D.; Rosemarie Hemmings, Ph.D.; and, Megan Herink, Pharm.D. Also involved is Andrea Gough-Goldman, M.D., M.P.H., of CODA, Inc.

The Pain Management and Substance Abuse Disorder in Dental Settings training’s next series will begin Jan. 4, 2023. More information is available online. Advanced registration is required.

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OHSU model reduces opioid prescribing

Erik Robinson — Mon, 08 Nov 2021 22:00:00 GMT

A graphic shows IMC high dose opioid vs buprenorphine. (OHSU/David Riofrio)

An internal medicine clinic at Oregon Health & Science University has sharply reduced the amount of opioids prescribed though innovative use of a review board comprising a team of health care professionals from various disciplines to ensure patients’ needs are being met.

This opioid review board advises OHSU primary care and internal medicine providers seeing patients who had been prescribed powerful and addictive pain-killers.

Their experience was published today in the journal Annals of Family Medicine.

“Once we began to discuss these cases, our numbers really began to come down quite steadily,” said co-author Mary Pickett, M.D., associate professor of medicine (general internal medicine and geriatrics) in the OHSU School of Medicine.

In 2016, the Centers for Disease Control and Prevention adopted a landmark set of opioid-prescribing guidelines. The guidelines, which happened to be co-authored by Roger Chou, M.D., director of the Pacific Northwest Evidence-based Practice Center at OHSU, were intended to ensure patients have access to safer, more effective chronic pain treatment while reducing the number of people who misuse or overdose from opioids.

OHSU internal medicine clinicians had been focused on safe prescribing well ahead of the CDC guidelines, but starting in 2017, the board began to systematically review high-risk cases in the clinic.

“The question was, how do clinics actually implement those guidelines in practice?” said Jonathan Robbins, M.D., assistant professor of medicine (general internal medicine and geriatrics) in the OHSU School of Medicine. “The opioid review board was a way to turn high-level recommendations into action steps we can take in our clinic to treat patients and create a culture of safe prescribing.”

Patients sign a waiver to have their treatment reviewed by the board, which meets monthly for an hour and comprises several physicians, a clinical pharmacist, a licensed clinical social worker, a medical assistant, a patient access specialist and a medical resident. The clinic started by reviewing treatment of patients being prescribed more than 90 morphine equivalent daily doses, or MEDD.

The clinic used electronic search methods to review a large volume of patient records.

“We combed through 14,000 patients in our clinic and developed a registry about who we’re chronically treating with opioids,” Pickett said. “We picked out high-risk cases to review and invited those patients’ primary care doctors to consult with us.”

The group initially identified 664 patients on chronic opioid therapy.

“We’re coaching primary care providers to approach this carefully, and, when necessary, slowly taper their patients,” Robbins said. “We don’t do anything abruptly, and patients have supported this careful process.”

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Opioid prescribing: ‘We’ve been able to change the culture’

Erik Robinson — Tue, 20 Nov 2018 21:50:00 GMT

David Knierim (left) of Wilsonville, OR, meets with his surgeon, Maisie Shindo, M.D., for an exam following his thyroid surgery. Shindo led an initiative to reduce the use of opioids for patients undergoing thyroid and parathyroid surgery. (OHSU/Kristyna Wentz-Graff)

Alarmed by the opioid crisis gripping the country, OHSU physician Maisie Shindo, M.D., decided to take action.

In the fall of 2016, Shindo, surgical director of the OHSU Thyroid and Parathyroid Center, led an initiative to sharply reduce the use of powerful opioids among patients undergoing thyroid and parathyroid surgery (the high-volume center conducts 300 to 400 endocrine-related procedures annually). The initiative has paid off. With the support of the hospital’s nursing staff, more than half of all patients who have had their thyroid or parathyroid glands removed go home with no opioids at all.

And patients seem to prefer it.

“The more you prescribe, the more patients think they need it,” said Shindo, a professor of otolaryngology/head and neck surgery in the OHSU School of Medicine. “Now we tell patients that some form of discomfort and pain is normal and there are ways to manage it without opioids.”

David Knierim, a 62-year-old engineer from Wilsonville, recently underwent two procedures to remove his thyroid gland due to cancer. He came out of each procedure with very little pain and relieved that he needed only over-the-counter acetaminophen. A key advantage for Knierim: Because he was able to think clearly without opioids, he was able to work from home starting the day after surgery.

Shindo had prepared him ahead of time, so he wasn’t surprised.

“I was expecting it to be tolerable,” he said. “Finding out that I wasn’t going to be on opioids was definitely a side benefit.”

Maisie Shindo, M.D., (left) talks with David Knierim during a follow-up exam, November 2018. (OHSU/Kristyna Wentz-Graff)

Shindo recalls prescribing Tylenol with codeine when she started her career in the 1970s. Then, beginning in the 1990s, the medical profession stepped up its focus on helping patients reduce pain associated with surgery. Pharmaceutical companies began marketing opioids heavily, and opioid prescriptions rose accordingly. Widespread use of prescription opioids led to misuse, addiction and overdoses. In 2017 alone, more than 72,000 people died from overdoses in the United States.

Reversing this trend took a change in culture, Shindo said.

Shindo said the reduction in opioid prescribing in OHSU’s Thyroid and Parathyroid Program required the buy-in of the recovery room nurses, who directly tend to patients in the hospital following surgery. Amy Stone, R.N., recalled speaking with Shindo about the right amount of powerful pain medications following surgery – and questioning whether they were necessary at all after certain surgeries.

“I experienced that same kind of ‘ah-ha’ moment,” Stone said. “I used to do follow-up phone calls with patients and remember one patient saying to me that she was upset or concerned that she went home with 120 pain pills and only used one of them. I recall thinking, we’re overdoing it here.”

Through an OHSU nursing fellowship program, Stone and a colleague subsequently developed a presentation to share evidence-based research about post-operative pain management and opioids with nursing staff.

Shindo recently co-authored a retrospective review published in the journal JAMA Otolaryngology-Head & Neck Surgery that documented a sharp reduction in opioid prescribing among thyroid and parathyroid patients at OHSU. The study showed a sharp decrease in opioid prescribing through the end of 2017. Since then, the downward trend has continued.

“We’ve been able to change the culture,” Shindo said.

In her endocrine cases, Shindo rarely prescribes any opioids in patients who have not previously taken them. She has been active in encouraging other clinicians to minimize opioids for patients undergoing endocrine surgery.

Percentage of patients discharged without opioids

Procedure 2016-17 2017-18

Parathyroidectomy 39.5 percent 78.1 percent

Hemi-thyroidectomy 19.6 percent 64.9 percent

Total thyroidectomy 17.5 percent 54.9 percent

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Many patients receive the wrong care for low back pain

Erik Robinson — Wed, 21 Mar 2018 18:46:00 GMT

Low back pain affects an estimated 540 million people at any one time worldwide, yet a new series of papers published today in The Lancet highlights the fact that for many people treatment is both expensive and ineffective.

Roger Chou, M.D.

“Despite increasing use of expensive treatments like surgeries, imaging and opioids, data indicate that the number of people with low back pain, and disability due to low back pain, has increased, not decreased,” said co-author Roger Chou, M.D., director of the Pacific Northwest Evidence-based Practice Center at OHSU.

Evidence suggests that low back pain should be managed in primary care, according to the authors, with the first line of treatment being education and advice to keep active and at work.

Low back pain results in 2.7 million emergency visits in the U.S. each year, with high rates of opioid prescription, according to one study cited in The Lancet. Another study found that opioids were prescribed in more than half of emergency department visits for low back pain in the U.S. as of 2009.

At the same time, a Global Burden of Disease study in 2017 found that low back pain remains the leading cause of disability in almost all high-income countries as well as central Europe, Eastern Europe, North Africa and the Middle East and parts of Latin America.

Listen: Dr. Roger Chou talks about treatment options for low back pain

The authors of the Lancet series wrote that health care systems should emphasize treatments that are safe, effective and cost-effective. They also highlight the need to address widespread misconceptions in the population and among health professionals about the causes, prognosis and effectiveness of different treatments for low back pain.

Previously, Chou co-authored a set of opioid-prescribing guidelines issued by the U.S. Centers for Disease Control and Prevention in 2016. The guidelines provide a set of clinical practice recommendations to help primary care physicians ensure patients have access to safer, more effective chronic pain treatment while reducing the number of people who misuse or overdose from these drugs.

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Procedure	2016-17	2017-18
Parathyroidectomy	39.5 percent	78.1 percent
Hemi-thyroidectomy	19.6 percent	64.9 percent
Total thyroidectomy	17.5 percent	54.9 percent