History of Pain: The Nature of Pain

History of Pain: The Nature of PainPractical Pain Management – November 21, 2013  

This is a long, informative article explaining how pain happens.

Our thinking regarding the nature of pain has shifted over the past four centuries from the linear dualistic concepts of Descartes to the Gate Control Theory of Pain, a more global model that includes affective components of pain

The evolution of scientific research has helped us appreciate that the pain experience is more complex and highly multifaceted from the subjective to the specific.

This article will discuss the nature of pain with some general assumptions based on our current understanding and then move to more specific considerations.  

Subjective Nature of Pain

The pain experience can change on a moment’s notice, depending on the external demands imposed on our nervous system. So why is it so difficult to accept the subjective nature of pain?

One explanation is that the nature of science has been based on the empirical search for cause-and-effect relationships and the scientific community is uncomfortable with subjective data.

Second, the individual nature of the pain experience is highly variable

Third, pain is a perceptual experience, which involves multiple integrated systems that act in a coordinated fashion

Further, it is important to consider that perception has thresholds, which can be explained by modifications in the periphery after injury or inflammation.

Loeser’s Model of Pain

The main difference between the two models is that the Melzack and Casey model is circular in nature and all of the components are interdependent. The Loeser model, by contrast, is linear in nature. Accumulating research suggests that our nervous system is highly integrated, interdependent, and reciprocal in nature.

Definition of Pain

The definition that predominates research is promulgated by the International Association for the Study of Pain (IASP): “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”7 IASP also added that pain is a subjective experience. It is associated with our perception of the event and influenced by our past experiences.

Acute vs Chronic

The expected timeframe is a hotly debated topic, but, generally, it is felt that pain persisting longer than 3 to 6 months (outside the expected timeframe of recovery) is considered chronic.

How Pain Works

From nociceptive stimulation to perception, it is now known that a whole series of endogenous mechanisms influence our experience of pain. These excitatory and inhibitory mechanisms may increase or reduce the nociceptive signal that translates into more or less intense pain

So how does this process begin? To answer this question we need to introduce the term transduction: the process by which the energy of a stimulus is transformed into an electrical response.

How does the energy of a stimulus transfer into an electrical response? According to current thinking, the nociceptor has more than one transduction mechanism that result from direct excitation or through receptor cells

Continuous painful stimulation results in sensitizing the CNS, which contributes to the pain experience. There are three categories of pain fibers as described in Table 1.

Categories of Pain Fibers

Pathways of Pain Reception And Transmission

Over the course of my pain practice, many of my patients have experienced radiating pain.

This type of pain is quite different from pain generated from the periphery, which implier a different function

The condition has different transmission speeds and the precise location does not assume the same importance. Further, radiating pain often develops gradually.

We must remember that the body will protect itself when injured by forming a natural splint, which compounds the pain experience by adding another source of pain.

radiating pain follows certain zones called dermatones.

The path radiating pain follows throughout the different zones will pass through different segments in the spinal cord.


There are two important concepts that need to be introduced in order to fully appreciate the pain experience at the neurophysiological level.

First is temporal summation, which results from different speeds between the faster and slower fibers (A-delta and C fibers)

high frequency repetitive nociceptive afferent stimulation will produce a temporal summation of the nociceptive afferent impulses originating from the slower C fibers

This accumulation of nociceptive activity within the spinal cord is called wind up, which contributes to spinal sensitization.”

The next important concept to consider is spinal sensitization,

Spinal sensitization is defined as “an increase in excitability and spontaneous discharge of the dorsal horn neurons of the spinal cord, an expansion of receptor fields, and an increase in responses evoked by the stimulation of small caliber fibers (hyperalgesia) and large caliber fibers (allodynia).”

Periphery to CNS

As the pain signal progresses to the dorsal horns (region of the spinal cord where afferent fibers enter the spinal cord) from the periphery, the fibers are separated into two groups: The large fibers, A-beta, enter on the dorsal medial side; and the smaller fibers, A-delta and C fibers, enter on the ventrolateral position

Dorsal Horns

The workings of the dorsal horn becomes very interesting because different fibers are coming together from different systems that connect with each other.

we need to discuss what happens to the pain signal once it enters the CNS.

Basically, there are three types of neurons that play a specific role.

First, there are projection neurons; neurons with long axons that link it to remote parts of the nervous system, muscles, or glands.

Second, there are excitatory interneurons; these are neurons that send the signal from one cell to another and connect signals that are transmitted from the CNS to PNS (peripheral nervous system or efferent neurons).

Third, there are inhibitory neurons that prevent activation of the receiving cell.

As the pain signal exits the dorsal horn, the pain pathway becomes more unpredictable based on surgical outcome data.   

One pathway that is important to our discussion is the spinoreticulothalamic tract. This pathway is composed of axons that travel from the spinal cord to the brainstem reticular formation before establishing their connection with the thalamus. This tract is divided into the lateral and medial tracts and both are responsible for pain transmission and project to the thalamus

Spinoreticular Tract

four cerebral centers that play a role in the pain experience. They are the primary and secondary somatosensory cortex, which processes sensory information (touch, temperature and pain) and is connected to the sensory-discriminative components of pain.

The third is the anterior cingulate cortex, which is located under the temporal lobe. This part of the cortex is part of the old brain or limbic system. Evidence suggests that the anterior cingulate cortex plays an important role in the motivational-affective part of the pain experience.

Finally there is the insular cortex, which is located deep within the temporal and frontal lobes. Recent evidence now suggests that this center plays an important role in the affective component of pain.


The Gate Control Theory of Pain influenced our thinking away from linear pain transmission to a model that asserted that the pain signal is modulated once it enters the CNS. Modulation can act either in an excitatory manner, where the pain signal is increased, or in an inhibitory fashion, where the pain signal is decreased or absent. It is important to consider that when inhibition is interrupted, it can result in chronic pain.

A number of neurotransmitters are associated with the inhibition system, including serotonin (5-hydroxytryptamine or 5-HT), which is a monamine neurotransmitter that plays a role in temperature regulation, sensory perception, and sleep. Next is norepinephrine, a neurotransmitter that belongs to the catecholamines. It is produced both in the brain and in the PNS, sympathetic division of the autonomic nervous system, and produces a variety of behavioral effects including pain inhibition. There is gamma-aminobytyric acid (GABA), an amino acid transmitter operating in the brain whose main function is to inhibit neuronal firing.  

Higher Centers of CNS

A number of regions in the higher cortex are involved in pain perception, which relate to the sensory-discriminative component of the Gate Control Theory of Pain. The interaction between higher centers and the limbic structures play a role in the motivational-affective component of the theory. Both of these influences contribute to pain modulation


Our knowledge of the pain experience has moved forward from a simple linear, dualistic model to a more global, intricate model that includes the importance of affective or emotional influences. Advances in neurophysiology and neuroanatomy have improved our knowledge with regard to the role modulation plays in the pain experience.  

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