Pain is an emotional experience that everyone would encounter in life. Unlike parameters such as body temperature and heart rate, pain is an abstract concept that cannot be objectively measured; it is greatly influenced by factors such as age, gender, preexisting medical conditions, social and cultural norms (Strong et al, 2002, p. 4). For instance two individuals that are suffering from the same course of disease might have entirely different responses to their pain, just as one would to daily situations in life. The International Association for Study of Pain (IASP) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (Loeser & Bogduk, 1994, p. 210). In another words, pain does not only consists of actual physiological changes (actual biological changes to the body tissue), but also to a certain extent psychological processing within that person. It is because of the complexity and multidimensional façade of pain that makes it so interesting. Understanding gained from recent studies allowed us to understand how all these dimensions interact within the nervous system.

Loeser proposed that pain can be meaningfully divided into four categories; they are Nociception, Perception of pain, Suffering and Pain Behaviour.

Nociception is the start of the pain process where tissue damage is first detected and information transmitted to the brain. Perception of pain is the human interpretation of the unpleasant sensation as a result of the tissue damage. Although tissue damage is involved most of the time, pain can also occur without nociception. Suffering is the association of negative response to pain or emotional events such as fear and anxiety. Verbal and non-verbal behaviours such as taking medication, refusing to return to work, and going to the doctor are considered to be pain behaviours. It is the outward manifestation that is communicated by the individual suffering from pain. These actions are observable and are commonly used by medical professionals to assess the level of pain. Fear avoidance is also a common pain behaviour whereby the individual avoids activities because of fear of re-injury and physical harm. In recent years, many pain assessment questionnaires are developed to measure the level of disability as a result of pain. In the following paragraphs you will realize that your attitude towards pain can influence the level of pain, disability and your physical recovery.

Classification of pain

Classifying pain in terms of duration is one way. Acute pain is elicited by substantial local tissue damage; it is a warning of actual or potential physiological harm. It starts on the first onset of injury lasting for about a 1 week. Subacute pain lasts between 1 week to 3 months after the onset of injury. While chronic pain is considered as pain lasting more than 3 to 6 month after injury. Those who experience chronic pain normally indicate failure of normal tissue healing or abnormal changes on the central nervous system.

Pain can also be classified as Physiological and Pathological pain. Physiological pain acts as a protective mechanism warning the body of potentially damaging stimuli, the receptors that operates in this type of pain is very sensitive in detecting non-harmful stimuli such as touch or pressure. For example, if a friend pinches your skin at the forearm, you will almost instinctively move your arm away due to the discomfort. This protective mechanism is called withdrawal reflex. On the other hand, Pathological pain does not involve the protective mechanism. It always occurs after a trauma or injuries associated with damage to the body tissue and nervous system. Those who seek medical assistance are normally those who suffer from Pathological pain. Injuries causing pain can range from a sprained ankle, back pain, fractures, nerve damage to spinal cord injury.

The Human Pain Pathway

Before we explore further into the pain pathway, there are some structures of the nervous system that you might need to be familiar with:

• Neuron – A specialized cell where messages in the form of electric impulse are conducted. Some neurons vary in shape and also in length, relaying information from one to another.
• Axon – It is a long process that extends away from the cell body, it continues to pass along the electrical impulse.
• Myelin – An axon may or may not be surrounded by the lipid substance called myelin, which acts as an insulator for the electrical impulse. (Formed by Schwann cells) The myelin sheath facilitate the conduction of the electrical impulses of the nerve cells.
• Synapse – The space between the terminal button of the neuron carrying the message and the dendrite of the neuron preparing to receive that message.
• Dorsal horn –A pair of slender, crescent-shaped projections of nerve cell bodies within the spinal cord.
• Free nerve endings: terminations of the Aδ and C fibers (pain relaying fibers)
• Nociceptors: receptors that respond to stimuli that cause tissue damage
• Hyperalgesia: increased pain in response to a painful stimulus
• Allodynia: pain in response to a non- painful stimulus
• High threshold receptor: receptor that is stimulated only by high level of stimuli

*  Neurological signs:

The pain pathway can be divided into four major sections, the Periphery, the Nerve and the Ascending and Descending pathways. At the periphery, beneath our skin, muscles and joints have receptors that detect sensations such as pain, touch, pressure, temperature and pain. Once these stimuli are detected, an intricate nerves pathway then relays these messages to the brain, allowing the higher centers of the brain to decipher the information. The individual then carry out appropriate actions based on the information received. In the following paragraphs you will learn in detail how these sections interact with one another.

Periphery

At the periphery, there is an extensive network of free nerve endings in the skin, muscles, and internal organs. They are terminations of the Aδ and C fibers, also known as the pain fibers. The pain fibers specialize in relaying pain signals to the spinal cord and subsequently through other structures to the brain for the individual to perceive pain. Nociceptors are also found in the periphery. They are abundant in the skin, joints and bones. According to Schmidt (1996) one third of the nociceptors are dormant until injuries occur, they are commonly activated by cell damage and inflammation.

When tissue injury occurs (eg, burn, cut, joint sprain, disc injury etc) chemicals from these damaged cells leak into the surrounding tissues. Small blood vessels surrounding the site of injury might also be torn due to the injuries. These lead to the release of a cocktail of “pain producing” chemicals consisting of Bradykinins, Leukotrienes, Prostagladin, Cytokines, Bradykinin, Histamine, Adenosine, Serotonin, H+ and K+. These chemicals cause dilation of the blood vessels (increasing blood flow), inflammation and tissue swelling which; in turn promote the release of even more pain chemicals. The “chemical soup” generated by this vicious loop then heightens the sensitivity of nociceptors, leading to an increased response to pain. This phenomenon is known as peripheral sensitization.

Tissue-damaging stimuli also produce effects that normally spread beyond the area of lesion. For example, after a skin cut, not only will the individual experience pain but also swelling, red flush at the site of injury and the surrounding tissue.

At the Nerve level , both painful and non- painful information in the form of electrical impulses travel towards the central nervous system (CNS). The pain fibers particularly the Aδ fiber and C fiber are activated. It is the small diameter Aδ fibers and relatively fast conducting nerve that carries the body’s initial response to pain. The small C fibers on the other hand are much slower carrying the prolonged nociceptive impulses, which continue even after the injury has taken place. It has been found that signals from C fibers are one of the main culprits for chronic pain. Repetitive C fibers stimulations result in hyperexcitablity of the dorsal horn such that they respond to stimuli in an exaggerated and prolonged way, directly increases the individual’s response to pain.

Recent studies indicated that the presence of constant and uncontrolled bombardment of impulses by pain fibers (C-fibers) over a period of time could change the level of neurochemicals in the processing units located in the dorsal horn. This leads to long lasting changes in the dorsal horn neurons making them hypersensitive to nocicpetive input. The process is called central sensitization (Woolf, 1996). Woolf and Costigan (1999) also found that nerves conducting non-painful signals start to acquire properties of pain nerve fibers after prolonged stimulation by pain signals. It has been demonstrated that peripheral injuries induce sprouting of non-pain fibers into areas of the dorsal horn that transmit pain signals. Once this occurs, non-painful impulses such as light touch and manual pressure might trigger painful impulses. This phenomenon is known as allodynia.

Therefore, with these new information gathered from the study of dorsal horn neurones we can conclude that the degree of tissue damage is not necessarily proportional to the level of pain.

Ascending pathway

The spinal cord is the super highway connected to the brain. It receives, transmit and modify in coming and outgoing information from the brain. The pain fibers enter the cord through the dorsal horn where they in turn are connected with interneurones or second order neurons called the spinothalamic tract. The spinothalamic tract crosses over to the opposite side of the spinal column almost immediately after it has entered the spinal cord and travels towards the cerebral cortex (the outer part of the brain).

The spinothalamic tract continues to ascend upwards ending at the thalamus of the brain. Thalamus, also known as the relay station is responsible for disseminating messages to other parts of the brain waiting further processing. The thalamus does perceive the pain, but it is not able to localize the source, it then sends that information on to the cerebral cortex and limbic system.

Limbic system

Recent knowledge suggest that emotion and behaviour are processed in the limbic system and the hypothalamus (Fox, 1996). In painful and distress situations, the pain signals can trigger a series of hormonal reaction initiated by the Hypothalumus leading to the release of stress hormone. Cortisol released in the adrenal gland found near the kidney region has been found to prepare the person for flight-or-fight behaviour. It has been found that prolonged pain can cause stress-induced response, which might contribute greatly to pain state. Prolonged pain state not only affects the cognitive aspect of the individual but also physiologically, it has been reported that heightened cortisol level in the circulatory system potentially reduce bone density and impede soft tissue recovery, further reducing the capacity for the body tissues to heal.

Cerebral cortex (Homunculus)

On a certain area in the cerebral cortex is a map of the human body, called the Homunculus or “little man”. Neurons in this location can identify the area of the body being stimulated by the information they receive from the somatic receptors in the skin (eg information such as touch, vibration, even pain). For example when your index right finger touched the screen of the computer monitor, electrical impulses are sent to a particular part of the sensory part of the cerebral cortex that represents the tip of the right index finger.

A particular body region is represented on the cortex with an area that is proportional to the density of touch receptors in the body part, not by its actual size. Since your right index finger is very dense with touch receptors, it takes up a lot of cortex compared to your arm. Therefore, the neurons form a geometrically distorted projection of the body surface (figure shown in Fig. 3). Similarly when an individual hurts the finger, he/she can easily localize the area of pain because of this map. Butler and Colleague (2000) suggested that central sensitivity to pain is closely linked to memory. Those who manifest maladaptive behaviour to pain has major component of their pain source being imprinted or represented within the homunculus. For instance, those suffering from chronic diseases such as chronic fibromyalgia and whiplash might acquire some sort of pain memory encoded within the Homunculus.

Descending pathway

Sometimes it is very important for the body to remove itself or one of its limbs from dangerous situations; therefore it must have a protective mechanism for drawing back. After the pain message has been processed in the brain, signals are sent back down the spinal cord to the appropriate area, and into a muscle, where it acts; this pathway is known as corticospinal tract, named because the impulse originates in the cortex and travels down the spine.

Descending pain inhibitory pathway can also be found in the spinal cord. Inhibitory effects are achieved through the descending pathways, which reach from the conscious brain down to the gates in the subconscious brain and the spinal cord. The reason for this is that the gates are places where the flow of pain messages can be controlled or influenced (Wells & Nown 1998). The brain can order the release of chemicals that have pain-relieving effects, which can reduce or inhibit painful sensation.

The descending pathway allows the brain to modulate painful sensation. The brain uses this pathway to send chemical substances and nerve impulses back down to the cells in the spinal cord to act against the pain message sent up by the pain receptors. After the “filtration” process, the remaining pain signals will ascend upwards to be perceived as pain. Hence, the primary role of the descending pathway is to send chemical messages from the brain to close the gates in the spinal cord to ascending messages (Catalano, 1987, Wells & Nown, 1998).

Descending inhibitory processes are of great interest in the research arena. Hence, it has been extensively studied by scientists. For instance, descending inhibitory processes have been investigated in anesthetized animals (Zimmerman 1984). It was found that the firing of dorsal horn neurons in response to tissue damaging heat can be inhibited by stimulation in the periaqueductal gray (PAG) and the lateral reticular formation (LRF) in the midbrain. In addition, inhibition of the spinal cord neurons can also be achieved by electrical stimulation in other regions of the brain, such as the raphe nuclei, the locus coeruleus, and various regions of the medullary reticular formation (for review, see Willis 1982; Mokha 1983; Morton et al. 1983; Gebhart et al. 1984), as well as sites in the hypothalamus, septum, orbital cortex, and sensorimotor cortex (Zimmerman 1984).

At the present it is not clear to what extent these different descending systems cooperate and interact, what their normal physiological functions are, and how they can be activated other than by electrical stimulation are not clear. They involve a very complex interaction of chemicals at the spinal cord and brain level.

Discogenic pain

The intervertebral disc is made up of 2 parts, namely the outer layer called annulus fibrosus and the inner jelly-like substance called nucleus pulposus. The nucleus pulposus is a semi-fluid mass consisting of 70%-90% water. It is because of the fluid nature of the nucleus pulposous that allows it to be deformed under pressure. A good analogy is a tyre of a motorvehicle, whereby the air tubing of the internal is the nucleus pulposus. When compression force is applied from any one direction to the tyre, it will deform, stretching the outer rubber rim. In the case of the intervetebral disc, the outer annulus fibrosus is the rubber rim. The annulus is made up of 50%-60% of collagen arranged in a highly ordered pattern. The collagen fibers are arranged between 10 to 20 sheets in concentric rings surrounding the nucleus pulposus, protecting it.

Traditionally leg pain or sciatica was believed to be due to pure mechanical compression of nerve root by the herniated disc, but pivotal studies in the past decade has implicated the involvement of inflammatory response. Emerging evidence has indicated that as a result of the damaged disc, substances such as tumour necrotic factor—Alpha, interleukines, nitric-oxide and synthetase will be emitted adding on to the inflammatory response. (Wuertz and Haglung, 2013). From the nucleus, pulposus leaks into the space where the adjacent nerve roots exits, resulting in nerve injuries. Although the mechanism of injury is not fully understood, such substances have been found to induce axonal and myelin sheath injury. Some researchers have proposed that the combination of increased inflammatory response and reduction in intraneural blood flow are probable causes of discogenic pain.

Illustration of a herniated intervertebral disc. Notice the interaction between the nucleus pulposus and the nerve root after rupture of the nucleus fibrosus.

Nerve trunk pain

Acute injury to the peripheral nerve rarely produces clinical pain, as cutting or compressing the trunk of an undamaged nerve produces only a brief discharge in the severed axons (Bennett, 1993). Within a few days after the trauma to the peripheral nerve, however, burning pain and mechanical sensitivity can develop at the site of injury.

Individual that suffers from nerve injuries may complain of symptoms such numbness, muscles spasm (involuntary muscular contraction), muscle weakness and diminished deep tendon reflexes. Pain resulting from nerve injuries, also known as neuropathic pain can generally be divided into 2 types, dyaesthesia and nerve trunk pain. Dyaesthsia results from a volley of impulses arising in the damaged or recovering pain receptors or sensory fibers (Beeton, 2003, p.78). It gives an abnormal sensation, frequently burning in nature, or electrical quality felt in region when sensation is diminished. The pain can also be a shooting or stabbing in nature. Allodynia can also be present indicating hyperexcitability of the nervous tissue.

Nerve trunk pain is attributed to increased activity in sensitized nociceptors within the nerve sheaths. The pain follows the course of the nerve trunk, giving a deep aching pain similar to a “toothache” and is worsened with movements, nerve stretch or pressure. There are speculations that nerve trunk pain occurs as a result of neurogenic inflammation (nerve inflammation) without the presence of actual mechanical nerve root compression.

In the lumbar spine, the most commonly cited form of nerve injury involves nerve root compression that usually involve a protruded intervertebral disc (PID), or slow growing osteophytes from the lumbar zygapophyseal joints. They can lead to nerve root compression in the intervertebral foramen leading to leg pain and neurological signs (Wiesel et al 1994). Although pain is not a necessary feature of nerve root compression, pain without the presence of inflammation can be due to nerve root compression (Bogduk, Twomey, 1991).

Nerve roots are blood ”thirsty”. A pressure gradient exists around the nerve tissue to ensure a constant flow of nutrients and oxygen to the nerve fiber. However, this gradient is disrupted by the nerve compression. The lack of oxygen supply to the nerve leads to swelling, pain and death eventually.

References:

Beeton KS. (2003) Manual therapy Masterclasses the Vertebral Column. London: Churchill Livingstone.

Strong J., Unruh AM., Wright A., and Baxter GD. (2002) Pain A textbook for therapist. London: Churchill Livingstone.

Wuertz K. and Haglung L. (2013) Inflammatory immediators in intervertebral disk degeneration and discogenic pain. Global Spine J. 3(3). 175-184.

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