Meeting News

Understanding the journey from acute to chronic pain

Jon Levine

TORONTO — Jon Levine, MD, PhD, of the University of California, San Francisco, conducted a clinical- and cellular-level exploration of how pain can transition from the acute to the chronic phase.

Levine raised questions about the generally accepted threshold of 3 months as the dividing line between acute and chronic pain. “When someone had pain for 3 months minus 1 day, we say they did not have chronic pain, but someone who had pain for 3 months plus one day did have chronic pain,” he said. He suggested that the picture is obviously more complicated than that.

Chronic pain can be broken down into three general types, according to Levine: acute pain that has persisted, a type of neuroplasticity, and analgesic-induced pain. Moreover, he suggested that induction, expression and maintenance comprise the three components of chronic pain. “These mechanisms are not necessarily the same in these aspects of chronic pain,” he said.

Acute pain that has persisted

“The major aspect I want to emphasize in the first type of chronic pain is that mechanisms involved are ongoing continuously,” he said. “They may change over time, but there is some process that is driving that pain.”

There may be a simple way of eliminating chronic pain, according to Levine. “The most important thing to do is eliminate the cause,” he said.

A straightforward example is degenerative arthritis in the hip. “The treatment is to eliminate the cause, meaning, replace the hip,” he said.

While therapeutic approaches can mediate pain and engage different targets at the cellular level, the clinical community remains largely at a loss as to how to truly remove pain from patients, according to Levine. “This illustrates the frustration that we all feel,” he said. “We give medications that approach these targets, but we have limited effect.”

Neuroplasticity, analgesia-induced chronic pain

Levine suggested that the neuroplasticity type of chronic pain, which is focused in the pain sensory system, is less clearly defined. “There is a set of properties that suggests what may be going on,” he said.

Experts are trying to understand the nature of the neuroplasticity as it pertains to chronic pain. Levine discussed a possible disconnect from mechanisms involved in the generation of that pain, namely the induction, expression and maintenance of pain.

He dug deep into the cell, discussing the use of TNF-alpha or IL-6 inhibitors in the nociceptor terminal to activate translation processes in the dendrites or axons. “We are trying to understand how pain operates at the cellular level,” he said. He explained that as time wears on and the patient continues to experience pain, the regulation of proteins can change at the cellular level, as can metabolic processes. In short, Levine suggested that prolonged pain can change the cellular regulation of that pain.

Levine drew an association between these processes and the way patients can develop resistance to NSAIDs. “We see early effectiveness, but there is lost effectiveness over time,” he said.

This brought the discussion to the third type of pain. He cited opioid-induced hypoalgesia as one example, along with certain migraine drugs that have caused patients to transition from having intermittent to chronic migraine headaches.

While the mechanisms of action of medication-induced pain are poorly understood, Levine highlighted one particular concern. “With opioid-induced hypoalgesia, onset does not take several days, it can occur in a matter of hours,” he said.

Cellular exploration of this type of chronic pain have yielded investigation into SRC and MEK inhibitors, along with MAP kinase inhibitors, according to Levine. “The drugs we use to treat pain may ultimately become part of this larger problem of chronic pain,” he said. – by Rob Volansky

Reference:
Levine J, et al. Plenary Session 4. Presented at: OARSI 2019 World Congress on Osteoarthritis; May 2-5; Toronto.

Disclosure: Levine reports no relevant financial disclosures.

Jon Levine

TORONTO — Jon Levine, MD, PhD, of the University of California, San Francisco, conducted a clinical- and cellular-level exploration of how pain can transition from the acute to the chronic phase.

Levine raised questions about the generally accepted threshold of 3 months as the dividing line between acute and chronic pain. “When someone had pain for 3 months minus 1 day, we say they did not have chronic pain, but someone who had pain for 3 months plus one day did have chronic pain,” he said. He suggested that the picture is obviously more complicated than that.

Chronic pain can be broken down into three general types, according to Levine: acute pain that has persisted, a type of neuroplasticity, and analgesic-induced pain. Moreover, he suggested that induction, expression and maintenance comprise the three components of chronic pain. “These mechanisms are not necessarily the same in these aspects of chronic pain,” he said.

Acute pain that has persisted

“The major aspect I want to emphasize in the first type of chronic pain is that mechanisms involved are ongoing continuously,” he said. “They may change over time, but there is some process that is driving that pain.”

There may be a simple way of eliminating chronic pain, according to Levine. “The most important thing to do is eliminate the cause,” he said.

A straightforward example is degenerative arthritis in the hip. “The treatment is to eliminate the cause, meaning, replace the hip,” he said.

While therapeutic approaches can mediate pain and engage different targets at the cellular level, the clinical community remains largely at a loss as to how to truly remove pain from patients, according to Levine. “This illustrates the frustration that we all feel,” he said. “We give medications that approach these targets, but we have limited effect.”

Neuroplasticity, analgesia-induced chronic pain

Levine suggested that the neuroplasticity type of chronic pain, which is focused in the pain sensory system, is less clearly defined. “There is a set of properties that suggests what may be going on,” he said.

Experts are trying to understand the nature of the neuroplasticity as it pertains to chronic pain. Levine discussed a possible disconnect from mechanisms involved in the generation of that pain, namely the induction, expression and maintenance of pain.

He dug deep into the cell, discussing the use of TNF-alpha or IL-6 inhibitors in the nociceptor terminal to activate translation processes in the dendrites or axons. “We are trying to understand how pain operates at the cellular level,” he said. He explained that as time wears on and the patient continues to experience pain, the regulation of proteins can change at the cellular level, as can metabolic processes. In short, Levine suggested that prolonged pain can change the cellular regulation of that pain.

PAGE BREAK

Levine drew an association between these processes and the way patients can develop resistance to NSAIDs. “We see early effectiveness, but there is lost effectiveness over time,” he said.

This brought the discussion to the third type of pain. He cited opioid-induced hypoalgesia as one example, along with certain migraine drugs that have caused patients to transition from having intermittent to chronic migraine headaches.

While the mechanisms of action of medication-induced pain are poorly understood, Levine highlighted one particular concern. “With opioid-induced hypoalgesia, onset does not take several days, it can occur in a matter of hours,” he said.

Cellular exploration of this type of chronic pain have yielded investigation into SRC and MEK inhibitors, along with MAP kinase inhibitors, according to Levine. “The drugs we use to treat pain may ultimately become part of this larger problem of chronic pain,” he said. – by Rob Volansky

Reference:
Levine J, et al. Plenary Session 4. Presented at: OARSI 2019 World Congress on Osteoarthritis; May 2-5; Toronto.

Disclosure: Levine reports no relevant financial disclosures.

    See more from Osteoarthritis Research Society International World Congress