Link between neglect, pain and harmful effects of painkillers identified

Researchers from Dundee’s Consortium Against Pain inEqualities (CAPE) set out to determine why exposure to neglect in early life increases vulnerability to pain and the detrimental effects of opioids in adulthood.

The body’s ability to tolerate pain is regulated by its own natural mechanisms, with the brain releasing opioids that can suppress pain. Using a mouse model, the team established that disrupted maternal care increased vulnerability to persistent pain.

In addition, morphine used to treat the pain was less effective than in those mice who hadn’t experience disrupted care. Importantly, morphine also caused rapid tolerance, a phenomenon associated with the development of opioid dependence and misuse.

The CAPE researchers found that the brain’s pain control mechanism becomes dysfunctional in mice after exposure to disrupted maternal care. These changes may explain why people exposed to childhood neglect and trauma are also prone to persistent pain and opioid dependence, findings with significant implications for the prescribing of painkillers.

Professor Tim Hales, Principal Investigator of CAPE, said, “We know that what happens in childhood can lead to multiple poor health outcomes in later life. The strongest association is with drug dependence. Psychological trauma and neglect cause physical changes in the brain so it is not surprising that that this can also increase vulnerability to pain.

“We believe that altered coping mechanisms caused by persistent stressors such as neglect in early life means some individuals are less able to regulate their pain and may also be less likely to benefit from opioid prescriptions, with vulnerability to their negative effects.

“I think this research will have an important impact as it identifies how this can happen.”

Chronic pain affects millions of people in the UK and is often linked to arthritis, cancer, fibromyalgia and other disorders. To help address treatment challenges and improve the lives of people affected by pain, a better understanding of the mechanisms and vulnerabilities is needed.

With opioid prescriptions linked to a rise in addiction and drug-related deaths across the world, there is also an urgent need to identify which patients are most likely to suffer harm because of exposure to these medicines.

Professor Hales continued, “Opioids have a role to play in treating pain, but they are potentially harmful drugs.

“Addiction is a complex, multi-factorial condition. The response to morphine of mice exposed to disrupted maternal care shows they have altered responses that may contribute to harmful effects of opioids. This provides a mechanism that may explain the link between childhood trauma and neglect in humans and increased drug harms in adulthood.

“A better understanding of the processes linking adverse early life events to chronic pain, will lead to changes in our approach to prescribing analgesic medications.”

CAPE was funded by a near-£3 million grant from UKRI. The paper is published in the journal PAIN and be read here.