Chronic Pain

Chronic pain extends beyond the healing of the injury that may have triggered it. It is defined as pain that lasts more than 6 months. Unlike acute pain, it serves no useful warning function. Chronic pain is not just acute pain that lasts longer, but involves different areas of the brain and spinal cord. One in five people in the US and Europe and one out of three people in China suffer from chronic pain. Disability from chronic pain, particularly chronic back pain costs society about 600 billion dollars a year, which is double the cost of cancer, heart disease and diabetes.

Although research has increased our knowledge of the mechanisms of chronic pain, there is still no effective treatment. Opioids, which work well for acute pain and pain at the end of life, do not work very well for chronic pain. Although they might provide some temporary relief, in the long run they make the pain worse. Opioid overdose has become one of the leading causes of death in the US.

In this post I will talk about the latest research about the mechanisms of chronic pain. Although we don’t have good treatments to reduce chronic pain, there are some interventions that reduce suffering from chronic pain and I will talk about those as well.

Types of Chronic Pain

Chronic pain can be divided into several types:

Chronic Primary Pain. This kind of pain is not related to injury. It includes things like fibromyalgia and myofascial pain syndrome.
Chronic Cancer Related Pain. Certain cancers can cause chronic pain even when the cancer is in remission
Chronic Post Surgical or Posttraumatic Pain. This kind of chronic pain starts with an injury or surgery as acute pain that transforms into chronic pain
Chronic Neuropathic Pain. This kind of chronic pain results from injury to the nerves or spinal cord.
Chronic Secondary Headache or Orofacial Pain. All of the secondary chronic pain conditions have a specific cause that starts the chronic pain. Fixing the cause, if it can be fixed, may not fix the pain.
Chronic Secondary Visceral Pain
Chronic Secondary Musculoskeletal Pain

Even though there are different types of chronic pain and different parts of the body where chronic pain is experienced, the mechanisms and pathways in the nervous system for chronic pain are the same. Chronic pain leads to actual structural changes in the brain and spinal cord.

Central Sensitization

Chronic pain starts with sensitization of the pain pathways in the spinal cord. This appears to be caused by inflammation in the nerve cells of the pain pathways. They start to respond with pain signals to any input from the skin nerves and often they just fire off on their own. The inflammation in the spinal cord is caused by chemicals called cytokines. Different people release different cytokines and some are more prone to cause chronic pain than others. That means that some people are genetically more likely to develop chronic pain. Not only a person’s genetic makeup, but which genes are expressed or inhibited also effect the genetic susceptibility to chronic pain. These are called epigenetic changes and these can be affected by a person’s life experience. People who have experienced trauma in childhood, called Adverse Childhood Events are also epigenetically more likely to develop sensitization of pain pathways and thus chronic pain.

The sensitization also spreads to structures in the brain, particularly in the medial pathway that goes to the emotional centers in the brain (see my previous post Pain to review the thee pain pathways in the central nervous system). These changes are associated with actual loss of nerve cells in those emotional centers.

Descending Pain inhibitory pathway in chronic pain

A meta-analysis of 92 studies of people with chronic pain showed that the lateral and the medial pain pathways were still active, but the descending pain inhibitory pathway was not. This suggests that at least part of chronic pain may be due to a deficiency in the descending pain suppression pathway. This may be particularly true for primary chronic pain syndromes like fibromyalgia and myofascial pain syndrome.

Chronic Pain as learning and memory

Pain is intimately connected with memory. From an evolutionary perspective it was important for animals to remember the conditions that led to pain so that they could avoid those conditions in the future. It appears that memory is part of what maintains chronic pain. The medial pain pathway, the pathway that goes to the emotional part of the brain also goes to the temporal lobes where memories are created. There is some evidence that chronic pain may be (a reward driven) maladaptive learning process analogous to the memory of traumatic events that cause PTSD.

The Microbiome

The billions of bacteria in our GI tracts are intimately involved in our health. They produce signal molecules that regulate inflammation and sensitization of the central nervous system. These signal molecules modulate brain activity directly. The composition of the microbiome may well be related to the development of chronic pain. This fascinating idea is the subject of much ongoing research.

Suffering

Suffering is defined as an anguishing experience, severely affecting a person at a psychophysical and existential level. People who suffer may experience fear, anger, frustration, anxiety and depression. It is important to remember that pain and suffering are different, have different pathways and go to different structures in the brain.

Catastrophizing

Tendency to magnify the threat of pain
Feeling helpless
Ruminating about pain

Catastrophizing can be caused by chronic pain, but people who tend to catastrophize about other things in life are more likely to develop chronic pain. Catastrophizing magnifies the suffering from chronic pain.

Treatment of Chronic Pain

People with chronic pain often get on a specialist treadmill, hoping to find a cause and a cure for their chronic pain. While occasionally a cause can be found that eliminates the pain, that is the exception rather than the rule. At present there are no really effective treatments for chronic pain. There are treatments that decrease the intensity of the pain and particularly that decrease suffering from chronic pain. For most people, the quest to eliminate chronic pain is unfortunately a fool’s errand. The first step toward having a good life despite the chronic pain is often to give up hope for a cure. I will discuss current treatments and potential side effects below. I will start with pharmacological treatments (medicines) and then go over other kinds of treatment, which may actually be more safe and effective than medicines. I will describe the pathways affected by each treatment

Opiates

Opiates, like morphine and oxycodone work in all three pain pathways. They increase the descending pain inhibitory pathway and decrease transmission through the lateral and medial pathways. Unfortunately, there is good evidence that long term use of opiates in chronic pain increase sensitivity to pain an effect called hyperalgesia. This leads to increasing doses to get the same relief. Opiates stimulate reward centers in the brain and are thus very addictive. They also depress the respiratory centers in the brain. Overdoses of opiates cause death by stopping breathing altogether. Opiates are too dangerous to use for chronic pain, and over the long term make the pain worse.

Treatments that activate the descending pain inhibitory pathway

Serotonin and Noradrenalin Re-uptake Inhibitors

These are the most common antidepressants in use today. The one that seems to work best for chronic pain is duloxetine (trade name Cymbalta). These medicines work on the descending pain inhibitory pathway. They do not help everyone with chronic pain, but some people get significant relief.

NSAIDS

The most common NSAIDs like ibuprofen and naproxen work primarily by activating the descending inhibitory pathway. Other NSAIDS that are called selective COX2 inhibitors work primarily in other pathways.

Exercise Therapy

Certain types of exercise, particularly Tai Chi, Baduanjin (a form of Chinese qigong) and stationary cycling activate the descending pain inhibitory pathway.

Acupuncture

Acupuncture blocks pain by activating the descending pain inhibitory system. This has been shown in both animal and human studies.

Brain Stimulation

This can be done non-invasively using a helmet that uses magnetic stimulation, or in intractable neuropathic pain it is sometimes done by electrodes implanted on the motor cortex. This activates the descending pain inhibitory pathway. Obviously implantation of electrodes in the brain is invasive and it does not alway give lasting relief.

Treatments that modulate the medial (suffering) pathway

Pain Killers

Acetaminophen (Tylenol) works primarily on the medial pathway. The same is true for specific Cox2 inhibitor NSAIDS such as celecoxib (Celebrex) and the injectable parecoxib. These NSAIDs also work on the lateral pathway.

Oxytocin

There is some evidence that an oxytocin nasal spray directly modulates the medial pathway. Clinical trials are underway to see if it helps chronic pain.

Mindfulness Meditation

There is increasing evidence that mindfulness meditation relieves suffering from chronic pain by directly affecting the medial pathway. It reduces or eliminates catastrophizing, which as I noted above magnifies suffering. There is also some evidence that meditation affects the lateral pathway as well, and sometimes (but not always) reduces the intensity of the pain. This approach was pioneered by Jon Kabat-Zinn in his Mindfulness Based Stress Reduction clinic in Worcester, Massachusetts. This approach is described in a very approachable way in his book, Full Catastrophe Living.

Treatments that modulate the lateral pathway

Aspirin

Aspirin at a 1000 mg dose modulates the lateral pathway, thus reducing the intensity of chronic pain

Gabapentin

Gabapentin, which was originally developed as a seizure medicine also reduces chronic pain via the lateral pathway to the somatosensory cortex. It does not work for everyone, and has some addiction potential.

Yoga

There is good evidence that yoga decreases the intensity of chronic pain by modulating the lateral pathway to the somatosensory cortex.

Acupuncture

It turns out that people with chronic pain get a double benefit from acupuncture. Acupuncture modulates the lateral pathway as well as the medial pathway.

Brain and spinal cord stimulation

These are invasive methods that are only used in the most intractable cases. They don’t always work.

The Bottom Line

Chronic pain is a different animal from acute pain. Sometimes acute pain transforms to chronic pain, but chronic pain can also occur without any preceding injury. It affects different parts of the brain than acute pain, primarily the emotional and learning centers in the brain. Chronic pain may be a reward driven maladaptive learning process. There are no effective treatments to eliminate chronic pain, but it is possible to reduce suffering from chronic pain and sometimes decrease the intensity. Although medicines are sometimes somewhat helpful, they all have troublesome side effects. Non-medicine treatments like exercise therapy, acupuncture, mindfulness meditation and yoga have minimal to no side effects and can reduce suffering from chronic pain and sometimes decrease the intensity of the pain as well.

The experience of pain is essential to humans. We live in a dangerous world and there are lots of things that can hurt us or kill us. The experience of pain warns our body-mind that damage is about to occur (or is occurring) and we immediately withdraw from whatever is causing the pain if we can. Almost all of this occurs at an unconscious level although there is definitely a conscious component to pain also. When we are injured pain forces us to rest the injured part until healing takes place. Once we have healed from the injury the pain goes away. It usually only lasts a few weeks at most.

People who can’t feel pain

To understand how important pain is to our survival, it is helpful to look at what happens when people are insensitive to pain. There is a rare condition called congenital insensitivity to pain. People who have this condition are able to feel touch normally, but are not able to feel pain at all. They sustain multiple injuries and rarely live past the age of 25. People with diabetes sometimes develop numbness in the feet and hands, called diabetic peripheral neuropathy. They are thus unable to feel pain in their feet. This leads to injuries and/or infections that they do not notice. It is common for diabetics with peripheral neuropathy to have amputations of toes or even feet because they can’t feel pain. Leprosy causes damage to skin nerves thus causing inability to feel pain. All of the deformities of leprosy are caused by injuries that are not painful to people with leprosy because their skin nerves are damaged.

Acute Pain

The kind of pain that both helps to keep us from being injured and helps us heal is called acute pain. There is another kind of pain that does not help us at all called chronic pain. More about chronic pain in the next post.

Pain Receptors

Humans (as well as other mammals) have four kinds of special pain receptors (nociceptors) in the skin. They only respond to damaging or potentially damaging input. There are mechanical nociceptors, which respond to pinching or pressure. There are temperature nociceptors that only respond to excessive heat. There are other temperature nocireceptors that only respond to excessive cold. Finally there are chemo nociceptors that respond only to damaging or potentially damaging chemicals.

There are also pain receptors in the intestines and the internal organs, mostly in the covering of those organs (called the peritoneum in the abdomen and the pleura in the lungs). These are much more difficult to study and not much is known about them other than that they are there and cause pain that is not very well localized.

Pain Pathways

There are three main pathways for pain in the nervous system:

Lateral pathway. This pathway goes from the nociceptors through a structure called the thalamus and then directly to the somatosensory cortex. The somatosensory cortex is located in the side of the brain called the parietal area and contains a map of the whole body. Sensations on the right side of the body connect to the left somatosensory cortex and sensations on the left side of the body connect to the right somatosensory cortex. This reverse order is because all the motor and sensory nerves from the spinal cord cross in the lower part of the brain called the brainstem and connect to the opposite side of the brain. The lateral pain pathway tells us exactly where the pain is coming from , how intense it is, and also the character of the pain (stabbing, pinching, hot, cold, etc).
Medial pathway. This pathway goes from the nociceptors to the thalamus and then to a part of the brain called the limbic system. This is the pathway to the emotion center of the brain. Pain thus causes an emotional response and lets us know how unpleasant the pain is. This pathway is where suffering starts to happen.
Inhibitory pathway. This pathway goes from a structure called the amygdala in the brain down to the spinal cord and blocks some of the pain from the other two pathways. This pathway works by releasing endorphins that attach to our opioid receptors. That is why synthetic opioids like morphine help relieve acute pain. They don’t work very well for chronic pain, as we shall see later.

Because of these three different pathways it is possible to feel pain without suffering and to experience suffering without pain. When these three pathways are balanced, we feel acute pain when we should, we find the experience unpleasant, and the pain goes away when we don’t need it anymore. When they are unbalanced, we can experience chronic pain, that is pain that persists beyond when it useful to the body-mind.

Pain and Memory

The experience of severe pain is also perceived in the hippocampus, which is in the temporal lobes of the brain and where memories are created and sent to other areas of the brain for storage. Pain creates instant and strong memories, so that humans and other animals can avoid situations that led to the pain. If you touch the metal handle of a hot frying pan, the memory of that pain ensures that you will use a hot pad from then on!

Bottom Line

Pain is essential to our survival as a species. As a result we and other animals have developed special sensors (nociceptors) that detect input that could damage our bodies or are damaging our bodies. There are two pathways through which the nociceptors send their messages to the brain, the lateral and the medial pathways. The lateral pathway goes to the sensorimotor cortex and allows us to feel the location, intensity and character of the pain. The medial pathway connects to our emotions and lets us know how unpleasant the pain is. That pathway is also where suffering occurs. The descending inhibitory pathway reduces our experience of pain both when getting away is the priority (think soldiers with war wounds who don’t feel pain until later) or when we have healed and don’t need the pain anymore. Chronic pain happens when these three pathways are out of balance. More on chronic pain in the next post.

Practical Health Information

What you need to know to have a healthier happier life. By Dr. John G. Scott