About This Research Topic
Pain is a complex sensory and emotional experience involving multiple pathways of the central nervous system, and these pathways are critical for different aspects of the pain experience. Recent advances in neuroimaging have completely changed the way we conceptualize pain processing and have led to a …
Keywords:Pain Processing, Brain Patterns, Neuroimaging, Non-Pharmacological Treatment, Pain Management, Human
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The General Pain Pathway
Within the pain pathway there are 3 orders of neurones that carry action potentials signalling pain:
- First-order neurones These are pseudounipolar neurones which have cells bodies within the dorsal root ganglion. They have one axon which splits into two branches, a peripheral branch and a central branch .
- Second-order neurones The cell bodies of these neurones are found in the Rexed laminae of the spinal cord, or in the nuclei of the cranial nerves within the brain stem. These neurones then decussate in the anterior white commissure of the spinal cord and ascend cranially in the spinothalamic tract to the ventral posterolateral nucleus of the thalamus.
- Third-order neurones The cell bodies of third-order neurones lie within the VPL of the thalamus. They project via the posterior limb of the internal capsule to terminate in the ipsilateral postcentral gyrus . The postcentral gyrus is somatotopically organised. Therefore, pain signals initiated in the hand will terminate in the area of the cortex dedicated to sensations of the hand.
The above is a simplistic generalisation for the pain pathway, however, a more detailed model is beyond the scope of this article.
Fig 1 A diagram demonstrating the simplified general pathway of nociception.
Sensing Pain: A Relay From Stubbed Toe To Brain
In your body, there are special sensory neurons called nociceptors whose job it is to tell the body this feels bad! . There are many different kinds of nociceptors some detect harmful chemicals , others harmful temperatures , and still others detect bodily damage . Nociceptors can also differ in the way they relay messages to the brain. Some, called A-fibers, have a fatty myelin sheath surrounding their long, arm-like axons that acts like insulation on a wire to help messages get to the brain quickly. These neurons were responsible for that first burst of pain in my big toe right when I stubbed it. Another type of nociceptor, called a C-fiber nociceptor, conducts signals much more slowly, but has many branches so that it reports to the brain from many different areas of the body. This type of nociceptor is associated with diffuse pain, and is likely to blame for that achey, burning feeling I have in the front of my foot right now.
Lets follow the stubbed toe message along its way to the brain. First, the message passes from my foot, up my leg, and into my spinal cord, where it is relayed to neurons whose fibers climb all the way to the brain. Up through the brainstem these fibers go, traveling in bundles to the brain itself where the message ping-pongs between the thalamus, hypothalamus, and a number of other regions scientists are just beginning to parse . The electrical communication between these regions gives rise to the feeling of pain.
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Extended Data Fig 8 Nonmetric Multidimensional Scaling
For the clustering of pain-predictive regions, we first ran the nonmetric multidimensional scaling on the Kendalls A distance matrix, which was calculated as /2. Based on the stress metric and scree method, we selected 10 dimensions . The x-axis of the scatter plot shows the input Kendalls A distance between regions, and the y-axis shows the Euclidean distance between the regions scaled into 10 dimensions after the NMDS. We performed the hierarchical clustering with average linkage on the selected NMDS results and used permutation tests to choose the final number of clusters, k. For the permutation tests, we shuffled the NMDS scores, applied the clustering algorithm, and assessed the clustering quality of the permuted data at each iteration. We ran a total of 1,000 iterations, and the plot shows the mean cluster quality of both the observed and permuted data, as well as the 95% confidence interval for the permuted cluster quality. The red square marks the selected solution with a Silhouette score of 0.59. The plot shows the z-scores that indicate an improvement of the cluster quality of the observed data compared to the permuted null data. The highest improvement was achieved with the 10 cluster solution with a z-score of 3.72, p=0.0002, two-tailed. The histogram depicts the observed cluster quality of the 10 cluster solution versus the null distribution from the permutation test .
How To Retrain Your Brains Pain Processing System
I recently read The Brains Way of Healing by Dr. Norman Doidge and learned about a fascinating way to retrain how chronic pain is processed in the brain. The approach, developed by pain specialist Dr. Michael Moskowitz, is used with people who have been in pain for an extended period of time and whose brains have essentially become oversensitive, heightening their experience of pain.
To understand how Moskowitzs method works, you must first understand how and why you feel pain. There are three types of pain that you can experience. The first, called nociceptive pain, occurs when nerve endings called nociceptors sense that damage is being done or is about to be done to your physical body. So when you cut your finger, step on a nail, or twist your ankle, you feel nociceptive pain.
Neuropathic pain occurs when structural damage is done to your nervous system: your brain, spinal cord, or peripheral nerves. This type of pain can result from an injury, autoimmune disorder, genetic condition, degenerative disease, stroke, vitamin deficiency, infection, toxins, diabetes, or alcoholism.
But if you believe that most or all of your pain is caused by adaptive changes in your nervous system that have caused you to experience an increasing amount of pain, then Dr. Moskowitzs approach could be exactly what you need.
How We Feel Pain
Pain is a complex physiological process. A pain message is transmitted to the brain by specialized nerve cells known as nociceptors, or pain receptors . When pain receptors are stimulated by temperature, pressure or chemicals, they release neurotransmitters within the cells. Neurotransmitters are chemical messengers in the nervous system that facilitate communication between nerve cells.
As seen in the diagram, these messengers transmit a pain signal from the pain receptor to the spinal cord, and then to the thalamus, a region of the brain. The thalamus then transmits the pain signal to other areas of the brain to be processed.
Once the brain has received and interpreted the pain message, it coordinates an appropriate response. The brain can send a signal back to the spinal cord and nerves to increase or decrease the severity of pain. For example, the brain can signal the release of natural painkillers known as endorphins. Alternately, the brain can direct the release of neurotransmitters that enhance pain or hormones that stimulate the immune system to respond to an injury. Recent research has shown that people possess differing amounts of these neurotransmitters, possibly explaining why some people experience pain more intensely than others. Furthermore, recent studies have found that genetic makeup can influence an individuals sensitivity to pain.
Types of Pain
What The Nervous System Does
Your nervous system is made up of two main parts: the brain and the spinal cord, which combine to form the central nervous system and the sensory and motor nerves, which form the peripheral nervous system. The names make it easy to picture: the brain and spinal cord are the hubs, while the sensory and motor nerves stretch out to provide access to all areas of the body.
Put simply, sensory nerves send impulses about what is happening in our environment to the brain via the spinal cord. The brain sends information back to the motor nerves, which help us perform actions. Its like having a very complicated inbox and outbox for everything.
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Clinical Relevance World Health Organisation Analgesic Ladder
The WHO has produced a step wise process for managing pain. There are 3 steps in this ladder, whereby if the pain is not controlled a patient will progress on to the next step.
- Step 1 Non-opioid +/- an adjuvant
- Step 2 Weak opioid +/- a non-opioid +/- an adjuvant
- Step 3 Strong opioid +/- a non-opioid +/- an adjuvant
The Battle Over Pain In The Brain
A new study adds to a heated debate about where pain signals are processed
Pain is an unpleasant but necessary sensation. The few people born without the ability to feel it must approach day-to-day tasks with extra caution. Without the ability to sense the effects of a broken bone or burned skin, its difficult to avoid harm. On the other hand, too much pain can be debilitating. Individuals with chronic pain often experience a host of additional negative effects on mental and physical health. Despite recent advances in uncovering the underlying mechanisms of pain perception in the brain, scientists are still debating the questions of where and how pain is processed.
Over the years neuroscientists have identified the pain matrix, a set of brain areas including the anterior cingulate cortex, thalamus and insula that consistently respond to painful stimuli. Some researchers have since applied this concept to conclude that that rejection hurts because social pain and physical pain share similar mechanisms in the brain. Others have suggested that brain imaging could be an objective measure of pain for diagnosis and drug development, and even as evidence in court.
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What Part Of The Brain Registers Pain
The brain stem, thalamus and cerebral cortex are the three structures of the brain that receive and process sensations of pain, according to BrainFacts.org. Different parts of the cerebral cortex are involved with painful sensations originating from specific parts of the body. Pain processing occurs in the sensory cortex.
Other regions of the brain are also associated with the perception of pain, according to Macalester College. Pain signals reach the brain through two different pathways, known as the fast pathway and the slow pathway. The fast pathway connects to the thalamus through A-delta fibers, which are neural pathways that transmit sensory information regarding pain and temperature to the brain. After pain signals reach the thalamus, they are then transferred to the sensory and motor sections of the cortex for further processing.
The slow pathway, as the name suggests, transmits pain signals less quickly than the fast pathway. The slow pathway begins with C-fibers detecting a painful stimulus through chemical, pressure or temperature changes. The C-fibers transmit sensory information to the dorsal horn of the spinal cord, activating the central nervous system. The sensory information travels through the central nervous system to various areas of the brain, including the prefrontal cortex, the amygdala and the hypothalamus. The slow pathway is associated with the emotional reaction that occurs in response to painful stimuli, states Macalester College.
The Role Of Nerves In Identifying Pain Sensations
Lets say you step on a rock. How does a sensory nerve in the peripheral nervous system know this is any different than something like a soft toy? Different sensory nerve fibers respond to different things and produce different chemical responses which determine how sensations are interpreted. Some nerves send signals associated with light touch, while others respond to deep pressure.
Special pain receptors called nociceptors activate whenever there has been an injury, or even a potential injury, such as breaking the skin or causing a large indentation. Even if the rock does not break your skin, the tissues in your foot become compressed enough to cause the nociceptors to fire off a response. Now, an impulse is heading through the nerve into the spinal cord, and eventually all the way to your brain. This happens within fractions of a second.
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Descending Modulation Of Pain
Within the central nervous system, there are three types of opioid receptors which regulate the neurotransmission of pain signals. These receptors are called mu, delta, and kappa opioid receptors.
They are all G protein-coupled receptors and their activation leads to a reduction in neurotransmitter release and cell hyperpolarisation, reducing cell excitability. Exogenous opioids, such as morphine, provide excellent analgesia by acting on these receptors. Likewise, our body contains endogenous opioids which can modulate pain physiologically. There are three types of endogenous opioids:
- -endorphins which predominately binds to mu opioid receptors
- Dynorphins which predominately bind to kappa opioid receptors
- Enkephalins which predominately bind to delta opioid receptors
Opioids can regulate pain on a number of levels, both within the spinal cord, brain stem, and cortex. Within the spinal cord, both dynorphins and enkephalins can act to reduce the transmission of pain signals in the dorsal horn. This is because the post-synaptic ends of second-order neurones have opioid receptors within the membrane. In addition, the pre-synaptic ends of first-order neurones contain opioid receptors.
Changes In Neurochemistry And Glial Cells
A survey of neurochemical changes in patients with chronic low back pain by proton magnetic resonance spectroscopy shows that chronic low back pain patients have reductions of NAA in the DLPFC, right M1, left somatosensory cortex, left anterior insula, and ACC glutamate in the ACC myo-inositol in the ACC and thalamus choline in the right SSC and glucose in the DLPFC, compared to controls . The translocator protein is associated with symptom severity and cerebral pain processing in patients with fibromyalgia. This protein is upregulated during glial activation, and compared to mixed/low TSPO affinity binders, high TSPO affinity binders rated more severe pain and fibromyalgia symptoms. Results are consistent with a glial-related mechanism of chronic pain .
Early life exposure to pain might predispose to later pain. This could occur through long-term changes in brain opioid receptors in the PFC and PAG, and may involve the gut microbiota and glial cells. Painful stimuli in the neonatal period produces pain behaviors immediately after injury that persist into adult life, and is accompanied by an increase in glial activation in cortical areas that process or interpret pain. These results suggest a role of glial cells in the PFC, in the chronification of pain .
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Brain Areas In The Neuromatrix And The Changes Due To Chronic Pain
Studies using functional MRI have identified six common regions activated in acute pain. These regions include the primary somatosensory cortex , secondary somatosensory cortex , anterior cingulated cortex, insular cortex, prefrontal cortex and the thalamus. It is these regions that make up the pain neuromatrix which Melzack has identified. More information on the Neuromatrix Theory of Pain and the Mature Organism Model can be found on the Multidimensional Nature of Pain page and on Louis Gifford’s website here.
The secondary somatosensory cortex is associated with the discrimination of pain intensity. There has been shown to be a co-activation between the primary somatosensory cortex and the secondary somatosensory cortex. In patients with chronic pain, there is a bilateral activation pattern, as compared to a contralateral activation pattern as seen in acute pain. This indicates that there is less of a representation of the initial pain and again may contribute to the widespread, vague pain described by chronic pain patients.
Transmission Of The Pain Signal
Axons travel throughout the body back to the spinal cord. Their pathways look like a tree, where the spinal cord is the main trunk with branches extending out into the body, and twigs and side shoots spreading again so all tissues are reached. A pictorial representation of this is called a dermatome map . This shows where the various nerves enter the spinal column. For example, the sensory nerves that supply the outer edge of the foot and the back of the leg enter the spinal cord in the sacral region. Damage to the sciatic nerve – which is the S1 nerve – results in sciatic pain, which is typified by extending down the back of the leg and into the outer foot.
The pain signal is rapidly conducted along the axon by the movement of sodium and potassium ions – like a series of action potentials being generated one after another in a wave of depolarisation. The signal travels more quickly in larger axons, and quickest of all when a nerve has a myelin sheath. The A-delta fibre is large and myelinated, and pain signals travel very quickly along this – providing us with first pain – an immediate, sharp painful sensation at the time of injury. The C fibre is small and unmyelinated, and carries pain signals slowly, giving us the dull aching sensation of second pain that follows.
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Acute Versus Chronic Pain
Pain may be acute or chronic. Acute pain begins suddenly and usually does not last long . Chronic pain Chronic Pain Chronic pain is pain that lasts or recurs for months or years. Usually, pain is considered chronic if it does one of the following: Lasts for more than 3 months Lasts for more than 1 month after… read more lasts for many months or years.
When severe, acute pain may cause anxiety, a rapid heart rate, an increased breathing rate, elevated blood pressure, sweating, and dilated pupils. Usually, chronic pain does not have these effects, but it may result in other problems, such as depression, disturbed sleep, decreased energy, a poor appetite, weight loss, decreased sex drive, and loss of interest in activities.