Opioid Abuse and the Need for Better Pain Medications

Designing Compounds

Philip PortogheseDistinguished Professor Philip Portoghese recently developed two new compounds that show promise as a breakthrough drug for treating chronic pain.

Many diseases or traumatic conditions are accompanied by inflammation that may lead to increased sensitivity to pain. Generally, the greater sensitivity is due to release of endogenous substances that make nerves that carry pain more sensitive. However, the opioid analgesics commonly prescribed today were originally evaluated on normal, noninflamed animal models.

Analgesics such as morphine, codeine, oxymorphone, oxycodone are generally effective analgesics for short term relief of pain. However, their efficacy usually declines upon chronic use due to tolerance.

“In an effort to develop medications that are effective for the pharmacotherapy of chronic pain without tolerance, we designed two compounds — MMG22 and MCC22 — that inhibit the action of inflammation-induced release of endogenous mediators that would promote pain sensitization of neurons while simultaneously stimulating opioid receptors in neurons,” said Portoghese.

Both MMG22 and MCC22 have analgesic activity equivalent to morphine in normal mice, but their potency becomes greatly amplified in inflamed mice. Additionally, no tolerance is evident for either of the

“In a chronic bone cancer mouse model, MMG22 was 3.6-million times greater than morphine,” said Portoghese. “MCC22 was found to be highly effective in the treatment of chronic pain resulting from chemotherapy-induced neuropathy and sickle cell disease.”

Both compounds are currently undergoing preclinical evaluation at the University of Minnesota.

Optimizing Pain Relief

Carolyn FairbanksProfessor Carolyn Fairbanks is also working to advance the understanding of the mechanisms underlying the development of chronic pain and to optimize innovative approaches to provide pain relief.

“Our approach is to develop strategies to activate inhibitory systems both independently of opioid analgesics and as synergistic partners to opioid analgesics,” she said. “Through synergistic combinations it is possible to access the powerful inhibitory systems of the opioid receptors with significantly lowered dose requirements, thereby reducing the risk of the well-known side effect limitations.”

Fairbanks’ goal is to refine and improve the effectiveness and safety of opioids and other analgesic medications to treat chronic pain.

Her research focuses on development of novel compounds or therapeutics with ideal characteristics for spinal delivery for pain relief.

“Spinal delivery of analgesics or gene therapeutics that activate or optimize inhibitory systems offers a very selective method of pain control that can increase the therapeutic index of such analgesics by reducing or eliminating their exposure to brain regions that mediate undesired side effects,” she said.

Fairbanks works extensively with U of M colleagues across other disciplines in research and in educational efforts regarding pain mechanisms and pain management. She is also connected with the national and international pain research community that is committed to addressing the global health problem of chronic pain.

Community-based Strategies

Laura PalombiAssistant Professor Laura Palombi works directly with communities in northern Minnesota to address heroin and opioid abuse in ways that make sense for specific communities.

The increase in heroin addictions has been especially problematic in northern Minnesota, where the number of people admitted for treatment and the number of deaths associated with heroin and opioids are higher than in any other part of the state.

“What works for one part of the state doesn’t work everywhere, and each community has different strengths that they can utilize to combat the drug abuse epidemic,” Palombi said.

One community-based approach is through the Carlton County Drug Court, which is a specialized, problem-solving court program that targets non-violent criminal offenders who suffer from addiction to drugs, including opioids, heroin, methamphetamine and marijuana.

“In lieu of incarceration, drug courts use a treatment-based approach in addition to intensive supervision and judicial oversight to support chemically-dependent participants in maintaining
sobriety,” Palombi said.

With colleagues in Carlton County, Palombi planned a successful Community Forum on Heroin and Opioid abuse. She is working to lead Drug Abuse Task Force efforts to reduce substance abuse in Carlton County, including educational programming for the community and a subsequent Community Forum. Palombi hopes to work with pharmacists across the state to coordinate more community-based efforts to decrease substance abuse.