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Researcher Discusses Neurological Underpinnings Of Pain


Woolf is the senior writer of a newly published research using optogenetics-a technique that uses hereditary engineering to render neurons in living cells sensitive to laser light. Using this process in mice, Woolf, and colleagues successfully identified the precise cascade of pain-related behavioral replies evoked by stimulating neurons that specifically sense pain-inducing stimuli.

The findings, published July 5 in Cell Reports, show some big surprises and cast a fresh light on the classic dogma of pain reflex responses first described a century ago by the neurophysiologist and Nobel laureate Sir Charles Sherrington. Woolf sat down with Harvard Medicine News to go over his latest research and his journey to unravel the mysteries of pain. HMN: Among the central themes in your quest is pain.

Woolf: When I was on the medical wards as a medical college student, there were many patients complaining of terrible postoperative pain. Why do we feel pain? Because it warns us of the danger in our environment. Without that warning, we are at high risk of damaging ourselves. Individuals delivered with congenital insensitivity to pain, for example, suffer repeated damage.

They’re not aware of the difference between food and their tongues, so they chew their tongues. They burn off themselves because they cannot differentiate between something warm or scalding hot. HMN: So pain is good, except when it is not? Woolf: Pain as a physiological response is absolutely good. It’s an integral adaptive mechanism that has a protective function against danger and is a warning transmission of infection, tissue damage, or disease.

Increasingly, we’ve come to identify that it also can become a disease in its right. This typically happens when the nervous system is damaged, and the initial trigger for the pain may long have disappeared but the pain persists. It no has a caution role but is now a pathological condition longer. The challenge then is to tease out the different kinds of pain to preserve the “good” pain and control the “bad” pain.

Here’s an example: If you injure yourself and you have pain, you mustn’t overly exercise the affected body part until recovery has occurred-that’s good pain, protecting the damaged tissues by making it a pain hypersensitive until it offers healed. But if you have damage to a peripheral nerve and experience episodes of shooting electrical-shock like pain, that pain has no protective function.

HMN: From biological and evolutionary factors of view, there are a few things we know about pain quite. But what exactly are a few of the challenges that lie ahead? Woolf: From an evolutionary perspective, even single cell organisms like an amoeba have to be able to identify their environment and respond to it by leaving any danger. So, the drive to detect potential harm has been there right at the beginning of the formation of living organisms.

Obviously as higher types with complex nervous systems progressed, it’s become much more complicated, involving feelings, mood, memory, and movement. Nevertheless, the pain is sufficiently important-80 percent of our peripheral sensory neurons are pain fighters activated by pinch, pinprick, excessive heat, or cold and other noxious stimuli. Whenever we sit, we squeeze the blood from our skin at the point of connection with the chair; if that persists, as it can in a few patients, they develop bed sores. Woolf: It is. That is physiological pain.

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Everyone thinks of pain as bad but it isn’t. That is why it’s critical in developing analgesics-you’ve got to protect these protective mechanisms and not switch off the entire system. That’s one of the big challenges. If you off change these danger signals, you’re going to create as many problems as you solve. In the clinical context, this means eliminating the pain that is pathological while protecting the pain that is protective. Today, it’s possible for individuals to live with severe harm to the anxious system, either their brain or their peripheral nerves, and survive. Evolution has not caught up with this.

In the hunter-gatherer culture, you wouldn’t have the ability to hunt and survive if you had damaged your sciatic nerve or spinal-cord, so there was no advantage to develop means of controlling chronic pathological pain. Now you can endure such accidental injuries and they are associated with severe pain typically. This is true also for the pain from the deteriorating of our anatomies. They are the age-related defects like the collapse of our intervertebral disks or the wearing out of the cartilage in our joints that before people didn’t live long enough to develop. Pain is the most common reason why people see a physician now. It also, obviously, was the trigger for the opioid epidemic.