Why Some Patients Need Higher Doses of Opioids

Why do some people require high dosages of opioids to manage their pain, while others only need low dosages, or even cope without? The answer depends on the person’s metabolism and the cause of the pain. A very small number of people have a rare chromosomal abnormality that affects how the person metabolizes the drug, making pain very difficult to treat. The other reason, researchers believe, is that unabated chronic pain (that is, pain lasting 3–6 months or longer) can in some cases structurally alter a person’s nervous system, leading to a disease state known as chronic pain syndrome. This alteration degrades the body’s normal pathways for pain management, requiring much higher doses for painkillers to be effective.

A common example of the development of CPS begins with a physical injury. In the initial “alarm stage,” the site of the injury activates neurons that carry the message to the brain, which then releases adrenaline and other hormones to aid survival.

The next stage is known as adaptation, where the body tries to adjust to the new situation and shifts from alarm to repair. However, if the pain remains severe for many months, the body eventually becomes exhausted. In exhaustion, the body may activate a normally dormant part of our genes, the result of which is to shift the mode of the pain signal transmission from the injury to the central nervous system itself. Researchers do not yet understand why this activation occurs.

Because the pain now has a different “source,” treating the injury will no longer help the pain. Instead, CPS is best managed by using medicine to suppress the pain round the clock, and long-acting opioids have been found to be the most successful treatment. Also, patients with CPS typically need larger doses of painkillers than are used to treat acute conditions.

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