More opioids, more pain: Fueling the fire

For more than a century, clinicians have noticed a paradoxical phenomenon: certain patients who are taking opioids (which are supposed to numb pain) become more sensitive to pain than those who are not taking opioids.

The earliest observation of this phenomenon can be traced back to the British physician Sir Clifford Allbutt, who, in 1870, described it: “at such times I have certainly felt it a great responsibility to say that pain, which I know is an evil, is less injurious than morphia, which may be an evil. Does morphia tend to encourage the very pain it pretends to relieve?” Research studies and clinical observations over the years have identified the phenomenon Dr. Allbutt noticed as opioid-induced hyperalgesia (OIH).

What is opioid-induced hyperalgesia?

Hyperalgesia is an increased pain response from a stimulus (cause) that usually provokes a minor pain response. For example, getting your blood drawn for lab testing usually causes mild discomfort, but this common medical procedure would be very painful for certain patients who are taking opioids chronically. OIH is a lesser known side effect of long-term opioid therapy, but a serious one, and yet another reason doctors should carefully select who may benefit from extended use of these pain medications.

What causes OIH?

The mechanism behind opioid-induced hyperalgesia is complex and involves molecular and chemical changes in the brain and spinal cord. Opioids tend to activate specific receptors that block painful signals from reaching the brain. When these medications are taken for long periods of time, our bodies (as a defense mechanism) try to overcome these blocked signals by activating other pain signals and pathways, a phenomenon known as hypersensitization. These changes reflect the incredible abilities of our brains to form new connections and pathways and alter how the circuits are connected in response to changes, also known as neuroplasticity. A positive example of this would be the rehabilitation process after a stroke: when someone suffers a stroke as a result of a clot or bleed in the brain and becomes unable to use their arm properly, the brain will start forming new connections in an attempt to overcome this deficit, and with proper rehabilitation and training a person may be able to use the arm normally again.

Who is at risk of developing OIH?

Pain perception is a very complex process. Many factors affect how the brain interprets pain signals. Anxiety, depression, genetics, medications, our physical health, and other illnesses can increase or decrease our feeling of pain. Just as pain perception is individual, the level of hyperalgesia is not the same in all patients; some people will experience more hyperalgesia based on their genetics and personal predisposition. Additionally, there is no well-established period of exposure after which OIH occurs, and the exact timing of someone developing OIH varies from patient-to-patient.