Physiology of Pain

The Physiology of Pain

Pain is one of a series of sensory systems in the human body, including the visual system (sight), the auditory system (hearing), the olfactory system (smell), the gustatory system (taste), and the somatosensory system (touch). While many consider pain to be a part of the somatosensory system/touch system, actually pain has its own dedicated pathways in the body and spinal cord, as well as its own unique areas in the brain. This makes sense when you think of what the purpose of the pain system is.

The pain system is designed as an early warning system. First, it is important to recognize that the pain system responds to stimuli that are approaching tissue damaging range. While pain responds when tissue damage occurs, the pain system actually responds significantly before that tissue damage happens. This is logical, when you consider the purpose of the system. Pain is designed to give you a warning signal. It is designed to allow you to get away from the stimulus that might hurt you. But this is not the only function of the pain system. It is also designed as a protective system - so that if you do have tissue damage or injury you will protect the damaged extremity/body part, to give it time to rest and heal. But when it comes to chronic pain, the first purpose can sometimes be the most important - in that patients can have significant pain, even when there is nothing “wrong,” where there are no identifiable injuries, no evidence of tissue damage. Similarly, a person can continue to have to pain even after that damage has long healed - because of adaptive systems that are somewhat unique to the pain sysstem. Finally, these pathways can malfunction, and someone can feel pain even in the complete absence of tissue damaging stimuli, or stimuli that are approaching tissue damaging range. In other words, a person can have pain even without any exposure to a potentially damaging stimulus, or may respond to stimuli that would not normally trigger a pain/nociceptive rseponse.

Nociceptors

Nociceptors are sensory receptors that encode pain information, or “noxious” stimulus receptors. Nociceptors are unique among sensory receptors, in that they can respond to a variety of stimuli, including pressure (mechanoreceptors), chemicals (chemoreceptors) and temperature (thermoreceptors). While there are many kinds of nociceptors, there are two general types - A fiber receptors and C fiber receptors. It is important to recognize these two major classes of nociceptors, because their functional purpose is quite different. For persons who are hurting, the difference in these two types of pain can have significiant implications for persons trying to deal with their pain.

C fibers

C fibers are primarily touch receptors - they respond to increasing amounts of pressure/pulling that can ultimately result in tissue damage. What is important about these receptors is that they begin firing long before tissue damage is actually happening. This is part of the pain system’s early warning function. If you put your finger on your arm, and press harder and harder and harder, when you first start to feel pain from that excess pressure, this is C fiber pain. That initial pain response is called a pain threshold.

C fibers are typically quite slow in their transmission speeds - they carry information at a rate of about 1 meter per second. The classic example of this is when you drop a weight on your foot, and it takes a second or two for you to actually feel the pain from the weight hitting your foot. This is C fiber pain.

C fiber pain is not focused - it tends to be very diffuse, dull, and aching in nature. While it does act as a warning system, anyone who has engaged in high level athletics knows very well that you can push through this type of pain relatively easily, particularly with practice. Again, just because you have dull and aching pain does not mean that you have actual tissue damage - it means that the stimuli are approaching tissue damaging range, and you need to be careful. However, it should be noted that chronic C fiber pain can also be quite debilitating, particularly because of its diffuse nature. But in general, mild to moderate levels of C fiber pain can be worked through without further damage to the body, without risk of serious injury.

A fibers

A fiber pain is strikingly different. A type nociceptors primarily respond to chemicals that are normally found inside cells - what this means is that they do not respond until cells are damaged, or once tissue damage occurs. They are extremely fast in their transmission speeds, some sending their signals at up to 100 meters/second. Most importantly, the character of A fiber pain is quite different, yielding often severe, very focused, sharp, intense pain. A fiber pain is not primarily designed as an early warning system, as C fiber pain tends to be. A fiber pain is often much more intense, and is designed to encourage the organism not to use the damaged body part, to allow for adequate healing.A fiber pain usually registers as much more unpleasant than C fiber pain, and is extremely difficult to work through.

What these differences mean

Being aware of these two types of pain can be very useful, particularly if you have pain and you are trying to increase your levels of activity. Dull, aching pain means you can proceed with caution. Sharp, lancing pain means you need to stop what you are doing, and try to find another kind of activity if possible. These differences can be used functionally, when trying to increase levels of activity when one is experiencing chronic pain. If the pain is sharp and focused, stop what you are doing, adn reassess the situation. If the pain is dull and aching, proceed with caution but do proceed.

Adaptation

One of the most important things to keep in mind about nociceptors and nociceptive pathways is that if they fire, you will perceive pain, even if nothing is wrong. This is eloquently seen in patients who have neuropathic pain, where they have pain not because they are encountering potentially tissue damaging stimuli, but because these pain receptors are often damaged, and are responding inappropriately.

Also, the pain systems are capable of a degree of learning, as they proceed up to the brain to register in conscious awareness. These potential modifications can have significant impacts on those who are experiencing chronic pain.

Pain Pathways

While some pain information is carried in the somatosensory/touch system, most pain signals travel through a dedicated pathway through the brain and spinal cord. Again, this emphasizes what an important system pain is in a functioning organism.

Nociceptors enter the spinal cord through the dorsal horn of the spinal cord, which is the same place where touch information enters the spinal cord. However, pain information crosses over to the opposite side of the spinal cord immediately, whereas touch information remains on the same side as it travels to the lower parts of the brain. An injury to the spinal cord can result in lose of pain on the opposite side of the body, and loss of touch on the same side as the injury.

Then pain information travels primarily through a tract called the spinothalamic tract. This travels to the lower parts of the brain, where it enters the thalamus, which is the primary relay system for most types of sensory information. The only sensory information that does not go through the thalamus is the sense of smell.

From the thalamus, pain is transmitted to the cerebral cortex, which allows for conscious perception of pain. Including primary and secondary somatosensory cortices, and parts of the anterior cingulate cortex, which is also involved with emotional reactions to pain, in addition to cognitive/motivational reactions.

In general, neurobiology research supports the notion that for pain to become perceived, it has to reach the cortical level. This becomes particularly important when you consider the descending control systems, the systems that go from the brain stem to the spinal cord, which can reduce or eliminate pain signals from reaching cortical levels. These structures are located in brainstem, and are regulated with the nsurotransmitter serotonin - this is one of the reasons why some antidepressants can actually reduce pain, in addition to assisting with mood disturbances.

As problems with nociceptors can cause pain in the absence of tissue damaging stimuli, strokes and other issues can lead to activity in other aspects of the higher pain systems. This can lead to the perception of pain in the absence of tissue damaging stimuli. In general, these issues are referred to as “central pain” issues.. Similarly, loss of pain inputs altogether can also result in abnormal pain, including after loss of a limb. This is called phantom limb pain The physiological phenomenon is called deafferentation pain, and can also result from spinal cord or brain lesions that eliminate pain inputs from the body.

Pain System Modifications After Exposure to Pain

Sensitization and Habituation

Pain is unique as a sensory system, in that it can be resistant to habituation. Habituation is what happens to you when you are exposed to a stimulus for a long period of time, and you basically get used to it, so you are no longer aware of it. Losing awareness of the watch on your wrist is an example of habituation - you will not feel the watch on your arm until you look at it. Because of the purpose of the pain system, it makes sense that habituation would not develop as it develops in other sensory systems. A person can habituate to pain, but this is much more difficult than with other sensory systems.

Also, the pain system can learn - what this means is that the amount of stimulation that is required to cause a nociceptor to respond can change. Clinically, the most important aspect of this response is a phenomenon called sensitization. If you have an injury for a long enough period of time, the thresholds for specific pain receptors can be lowered. A threshold is the minimal amount of stimulation required to make a given receptor activate. If you put a finger on your arm and press harder and harder and harder, when the pressure just becomes enough to hurt, this is your pain threshold for touch. An easy example of sensitization that most people can relate to for this phenomenon is how when you get a significant bruise, the skin around the bruise will become extremely sensitive to touch, so that stimuli that would not normally hurt you become frankly painful. That bruise becomes sensitized, so even light touch can become frankly painful

These features of the physiology of the pain system complicate evaluation of pain - because you can have pain in the absolute absence of tissue damage, and you can have tissue damage without pain. If a person has an experience of pain for a long time, like many back pain patients, the pain can remain even after the injury has healed. Similarly, there are many types of pain syndromes that appear to be related to lowered pain thresholds - like fibromyalgia and chronic regional pain syndrome.

Neurogenic pain syndromes

Some types of pain may be associated with changes in the pain pathway, that result in the lowering of pain thresholds, or the amount of stimuli you need to be exposed to that will result in pain. What this means is that stimuli that would not normally be pain inducing can become frankly painful. Fibromyalgia is offered considered to be a central pain or neurogenic pain system. There is no damage, no pathology, in the pain system, but the pain receptors fire even when there is no stimulus approaching tissue damaging range.

Neuropathic Pain

Many different kinds of damage that can occur in the peripheral and central nervous system can result in significant pain. This includes pain caused by damage to the nerves that carry pain information. Syndromes like multiple sclerosis attack the fatty layer that insulates the neurons in the nervous system. While the pain pathways do not have as much of this insulation as other pathways in the body, particularly A fiber pain fibers can be highly myelinated (myelin is the name of this fat layer). As the immune system attacks this myelin fatty layer, the neurons lose their insulation, and signals can bleed across neurons, which can result in frank pain.

Patients who have vascular disease or diabetes can also have damage occur to peripheral neurons, particularly in the extremities. This damage can lead initially to unusual sensations (burning and tingling), but if these issues are not managed, this can result in severe damage to neurons, which become hypersensitive as they are dying. Again, these people can feel pain even though they are not exposed to a noxious stimulus - the damaged neurons are firing abnormally, which produces pain. Ultimately, those peripheral sensory neurons can die, resulting in numbness - however, loss of these inputs can also result in deafferentation pain if those inputs are completely lost.

Pain pathway damage

If your body loses inputs from the pain systems, which are called sensory afferents, this can result in a syndrome called deafferentation pain. The specific mechanisms of these changes are not well understood, but apparently if you lose the inputs into the parts of the brain that code for pain, those areas of the brain can become hyperactive. Research has shown that this may be due to the fact that lateral areas of the brain surrounding the area that has lost its inputs may send new branches into the area that is not receiving inputs. This can lead to activity in that area even without any pain or nociceptive inputs- an example of this can be found in the syndrome of phantom pain, when a person loses a limb, but after a period of time the person starts to experience pain subjectively in the limb that are no longer part of the body.

Centralized pain

Centralized pain is a situation in which the components of the central nervous system appear to alter their reactivity, such that the thresholds for what the body would usually consider painful changes. So stimuli that would not normally be considered painful register consciously as pain.

“Learned” pain

In some cases, if a person experiences pain for a significant period of time, that pain can become associated with specific experiences, like bending over, specific movements, environments, or events. Actually being around certain people, who may respond to your pain in a specific way, can also change how you experience your pain. If someone is overly solicitous, this can actually increase your pain. Similarly, being around people who are respectful but who do not call attention to your pain, can help reduce the amount of pain you experience. These pain experience change may be a result of changing the amount of attention you are paying to your pain, but it also may be because you associate that person or place with pain, which may make you hyper vigilant to pain sensations.

Malingering

This is basically faking, or reporting pain in the absence of any sensory or perceptual experience associated with pain, for the purposes of getting some kind of reward, which can include attention, pain medications, or financial renumeration, such as claims of disability. It is important to note that malingering for pain is actually quite rare, particularly for those presenting for emergency care for pain. But in cases of malingering, there is no damage to the nervous system, no potentailly tissue damging stimuli - these people complain of pain that they are not actually feeling, often to get attention, support, or financial reasons. Again, this kind of malingering is relatively rare, but patients need to be aware that a clinician is evaluating a person in pain, they have to consider malingering.