Pain and Memory

we can't govern
Aug 9, 2017 · 4 min read

Life in the 21st century is a constant state of chronic pain. The slow collapse of our government and institutions, the hollowing out of our middle class, the rising threat of global warming; everything hurts now, in a vague, indefinable way, not tied to any specific injury but throbbing from somewhere within. Perhaps the opioid epidemic is merely a metaphor reified and writ large.

Then again, maybe people just hurt. Chronic pain is a serious problem. It’s largely invisible, tied to disorders like fibromyalgia and Lyme disease. It ebbs and flows, so if you have a good day and feel like you can take part in your normal activities, you are setting yourself up for chiding later when the pain gets to be too much and your loving friends and family ask what’s wrong with you. Chronic pain is intractable; that’s what makes it chronic. It can be pushed down and suppressed but it never goes away.

Typically, pain clinics treat chronic pain through a mixture of physical therapies (often useful when the pain is caused by an injury or burn) and medication. Opioids are common, as are less addictive pain meds such as gabapentin and ketamine. Some states allow medical marijuana, and cannabis are a remarkably effective treatment for pain that is also helpful with nausea. These treatments, however, come with their own problems. It’s easy to become sensitized to pain meds, and they lose effectiveness over time. They make you groggy, mess with your memory and coordination, make it hard to sleep… and even when they work, at best they can push the pain down and make it bearable for a few hours.

New research, however, is shedding new light on the root causes of chronic pain and hinting at the possibility of treatments that go beyond temporary suppression. At their core is a fundamental re-orientation of how we think about chronic pain.

Pain is a phenomenon in your brain. When you are injured, specialized nerves called nociceptors pick up the damage and transmit it to your central nervous system, where it registers as pain. That makes sense — if something burns or slices you, your brain should be alerted immediately, so it can react in time to save you from serious damage. The theory of “central nervous system sensitization” is that, sometimes, these pain impulses become “trapped” in your brain. The initial stimulus is long over, but the pain remains, echoing endlessly back and forth. You can’t stop it, because it should have stopped already; you can’t pull your hand away from the stove if you’re not touching it in the first place. It’s unclear why this happens, but according to this theory, it’s the memory of pain that’s hurting you, a memory you can’t forget. Over time, your brain can become more sensitized to pain, producing more pain with less stimulus (hyperalgesia) or even with no stimulus at all. This is thought to be behind Complex Regional Pain Syndrome, a rare form of chronic pain where a limb aches constantly and even the slightest movement or touch can cause an explosion of agony (allodynia, pain caused by normally painless sensations).

If chronic pain is caused by the brain refusing to forget about pain, then treating that pain requires directly targeting the brain. One extreme solution involves using ketamine to induce a coma in the sufferer, effectively “resetting” the nerves and causing them to “forget” the pain. This has proven effective at treating patients with otherwise intractable pain. Trials with rats have demonstrated that a protein known as PKMzeta, known to be essential for forming memories, also works to encode memories of pain. Mice suffering from hyperalgesia can be “cured” by neutralizing their PKMzeta with an enzyme called ZIP; someday, this could cure chronic pain in humans altogether, by erasing the “pain memory” that holds them in thrall.

This line of research also shows us how to prevent chronic pain in the first place. When memories are formed, they are vulnerable — disrupting this process of formation can prevent the pain memory from forming in the first place. This same technique can be applied later, to retroactively erase pain memories, as experiments on mice demonstrate. Anisomycin, an antibiotic, can inhibit the consolidation of long-term memories. This is how memories are stabilized by the brain after they first form, and by disrupting it, scientists can stop the memories from carving their traces in the soft tissue of your brain. Propranolol, a heart medication, is already being used to help humans overcome painful memories, and may have applications in the pain field as well. The antibiotic D-cycloserine has been tested as a treatment for back pain — it has been used as a treatment for phobias, removing the traces of fear associated with a normally benign stimulus. Doctors are hopeful that it will work on pain as well, and trials are ongoing.

A dizzying variety of anticonvulsants, antipsychotics, and antibiotics are all used off-label to treat chronic pain. As our understanding of the depth and severity of the opioid crisis grows, it is more important than ever that we find alternative treatments that can actually treat and cure chronic pain, not just temporarily bury it.

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