Nociception and Pain Perception: A Literature Review

The physical and psychological factors of nociception and pain perception in humans: A review. University of Vermont

The direct experience of pain is often defined via the conscious, as the degree to which we feel pain is based purely on psychological perception. There is, however, a physical component to pain, as pain perception relies on a stimulus and the transmission of the signal this stimulus produces. Inclusively, the transmission of signals following stimuli and the resulting sensory activity is known as nociception (FURST, 1999). Pain perception refers to the conscious processing and interpreting of these signals (BALDO, 1999). Recent advances in functional brain imaging and anatomical methods in animal studies have allowed researchers to examine the physical aspect of nociception on a neurological level, especially regarding the active components of the cerebral cortex within the nociceptive system. Here, there are two major somatosensory pathways working simultaneously.

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These pathways are broadly known as the lateral and medial pain systems (MELZACK, 1990). Both pathways work closely with the hypothalamus, which has exhibited a crucial role in pathway and cortex communication during nociception (MATHARU, 2007). These three components are active with pain that results from physical activation of tissues as well as pain that occurs without any peripheral physical input, such as psychogenic pain (BINZER et al., 2003). This suggests that the interaction between the somatosensory systems and the hypothalamus offers a connection between the physical aspect and psychological aspects of pain. Therefore, in order to understand the perception of pain, one must establish an understanding of these systems, but more so the interaction between them. Furthermore, by examining the abnormalities in pain perception – such as chronic psychogenic pain and phantom limb syndrome – we can develop a greater understanding of the nociceptive role of these sensory and hypothalamic pathways as well as their ability to alter our perception. This understanding will be crucial in developing analgesic therapies and treatments.

First, it is important to understand the nociceptive process. This physical pain process begins in the nociceptors. These are differentiated receptors found in free afferent nerve endings (FURST, 1999). In terms of synapse orders, these neurons are typically first-order neurons, distributed throughout the skin, vessels, muscles, joints and viscera (JULIUS et al., 2001). These are activated by a noxious stimulus bridging an electrical potential threshold (BURGESS et al., 1967; MILLAN, 1999). They are divided into three classes. Mechanoreceptors are sensitive to intense mechanical and motion stimuli, observed through the tension of tissues.

Thermoceptors, on the other hand, are specifically sensitive to thermal stimuli. Then, polymodal nociceptors are inclusively sensitive to mechanical, thermal and chemical stimuli, as well as inflammation sensations (TEIXEIRA et al., 1994; BESSON, 1999). All of these receptors show an increased sensitivity to continuous stimulation (CHEN,1996; LIEBESKIND, 1976). These stimuli promote a local release of chemical mediators – hystamine, serotonin, acetylcholine – that alter the membrane permeability of the nerve and allow for the propagation of an action potential (JULIUS et al., 2001).

The first-order neurons synapse along the spinal cord via afferent sensory fibers. A-beta fibers are slower conducting, myelinated fibers that respond to tactile stimuli. A-delta fibers, on the other hand, are myelinated fibers responsible for the fast conduction of painful stimuli. C fibers are unmyelinated and responsible for a slower form of transmission. C fibers are possibly the most active and prominent of the spinal fibers (FURST, 1999; GRUBB, 1998; SHELLEY et al., 1994). Pain seems to come in two steps: first, a quick and sharp pain, which is followed by a slow and dull pain. The A-delta fibers are thought to be responsible for the transmission of the “initial pain”, while the C fibers transmit the after effects of this pain (JULIUS et al., 2001). The peripheral nociceptors and their dorsal root ganglion cell bodies are located in the terminals of the first-order sensory neurons. They transmit the nociceptive information to the neurons of the dorsal horn of the spinal cord. The process itself, however, depends on calcium and sodium channels, which ensures the passing of action potentials while also assisting in the release of neurotransmitters (HILL, 2001).

After the first-order neurons synapse at the dorsal horn, the second-order neuronal axons form tracts. These tracts transmit the nociceptive impulses to structures of the brainstem and the midbrain, including the thalamus, reticular formation, amygdaloid complex and hypothalamus (ALMEIDA et al., 2004). Sensory information is transmitted via the anterolateral tract of the spinal cord, but the main pain pathways are found in the spinothalamic, reticulospinal and spinomesencephalic tracts (CAILLIET, 1999; MILLAN, 1999). The reticulospinal tract, a slower processing tract, runs medially through the brainstem. It projects to the thalamus, cortex and structures of the limbic system. The spinothalamic tract, a fast processing tract, continues laterally along the brain stem. It transmits projections to the ventrobasal thalamus and onwards to the sensory cortex (RUSSO et al., 1998). Another important pathway is the spinomesencephalic tract, which is found primarily in the midbrain. It is this tract that shows the most connectedness with the limbic system, particularly the hypothalamus (BALDO, 1999).

A number of neurotransmitters and receptors are being discovered between the areas of pain transmission and cognitive brain structures, such as the thalamus and hypothalamus. This indicates that there is a stronger degree of connectedness between these areas than first anticipated. For example, electrophysiological studies suggest glutamate and other excitatory amino acids act on glutamate-specialized ionotropic receptors and metabotropic receptors during the transmission of pain information from the spinothalamic tract to the thalamus, and from the spinomesencephalic tract to the hypothalamus (AZKUE et al., 1997; ERICSSON et al., 1995; JENSEN et al., 1992; SALT et al., 1996). The thalamus plays a fundamental role in the integration of the pain signal. Third–order neurons pass signals from the thalamus to the somatosensory cortex, where the stimulus is converted to a perception of pain (FÜRST, 1999). The hypothalamus, on the other hand, is strongly connected with the primal limbic system. This could possibly allow for an integration of a fear response to pain, as well as an emotional response (BALDO, 1999). According to Baldo (1999), while the hypothalamus does play a role in strict communication between the lower and higher order cognitive structure, this connection may also aid in the somatosensory perception of pain by supplying a form of a chemically driven emotional response. An important example of this emotional aspect of pain is seen in both enhancing the pain sensation and providing an analgesic effect
(MELZACK et al., 1999). The degree to which one perceives pain is not always directly proportionate to the intensity of the pain stimulus (MILLAN, 1999). This, therefore, highlights the connection between pain perception and self-experience. Having this connection is important defensively, as there is evidence that fear inhibits pain in humans (MILLAN, 1999). Bolles and Fanselow (1980) proposed a model for explaining the fear/pain relationship called the perceptual-defensive-recuperative (PFR) model. This model exemplifies how pain can lead to certain fear behaviors and vice versa. With painful stimulus, one either displays recuperative behavior, responsible for the recovery of the individual, or defensive behavior, which promotes environmental perception and defense (BOLLES et al., 1980). This being said, pain can either be inhibitory or excitatory to other systems, depending on the needed outcome (MILLAN, 1999).

The PDR model can be divided into three phases: perceptive, defensive and recuperative (BOLLES et al., 1980). The perceptive phase is merely the initial detection of stimulus, as seen in the initial stages of nociception. This, however, is a learned stimulus and serves as a signal for eliciting defensive behaviors based on previous experiences with pain. Thus, the conversion of nociception into pain involves factors such as cognitive aspects and emotional context. This is why there is an observed variance in how different individuals experience and categorize pain (MELZACK, 1999; BOLLES et al., 1980). The defensive phase is also individualized and involves the reaction to the stimulus occurring. Because of learned fear and pain, a sometimes immediate analgesic effect takes places. This is associated with the increased release of glutamate and the activation of the medulla. Therefore, fear and previous experience can draw out a learned response in the pain system, this response being a physical amendment to the descending pathways in the form of an analgesic effect.

This model suggests that top-down processing plays a major role in analgesia. Therefore, the descending pathways that run from the midbrain through the medulla to the dorsal horn of the spinal cord have an inhibitory effect upon distal structures or even an excitatory effect on the release of neurotransmitters. This supports the notion that there can also be a form of
top-down processing where higher control areas affect stimulus transmission in itself (MELZACK et al., 1965). This type of interaction, however, can sometimes be disadvantageous.

As mentioned previously, it is crucial for researchers to consider abnormalities in a system when exploring its physiology. These abnormalities often offer insight towards the overall connectedness of a system. Regarding pain perception, examining system abnormalities that take root in both the physical and psychological perspectives will theoretically yield a greater understanding of how the physical aspects of pain are psychologically received and how psychological aspect manifest physically.

One such abnormality is phantom limb syndrome. While there is a lot of ongoing research involving the syndrome, phantom limb syndrome is typically defined as a continued feeling of pain and sensation along the nerve endings of a previously amputated limb (GALLUZZI, 2007). This sensation ranges from a complete perceived image of the limb in space to the imagined ability to move the missing limb. Most notably, however, is a strong sense of pain associated with the cut nerves. This pain is often described as a dull, continuous pain with periods of brief, but sharp shots (GALLUZZI, 2007). Researchers, however, have debated whether this pain stems from a nociceptive defect or a defect in the perception of the limb and pain itself. Some researchers, for example, have speculated that the remaining A-delta fibers are continuing to fire, despite the severing of the first-order neurons (JULIUS, 1954). This would be due to the location of the amputation. According to Julius (1954), if an amputation occurs below a fundamental joint, such as the shoulder socket or elbow, the fibers responsible for initial pain indication may still be active. In terms of the anterolateral tract – previously discussed to be a major component in nociception – the pain signal crosses the body’s midline at the spinal column. There is, however, a small but significant ipsilateral component to this tract. Julius (1954) suggests that this ipsilateral component may result in a form of signal return similar to a continuous firing of nerves. If this is the case, the argument can be made that phantom limb syndrome is not a disorder involving a misuse of perception, but merely a defect in the
nociceptive transmission. Other researchers, however, have made the argument that phantom limb syndrome is a varying degree of chronic psychogenic pain. Chronic psychogenic pain is a form of continuous pain that lacks a physical stimulus. This pain is often associated with those with chronic illnesses as well as those who have been traumatized (BINZER et al., 2003). That being said, it is typically thought that psychogenic pain is a disorder of only perception, dealing mostly with conscious or subconscious rather than a physiological marker. Research has shown that the more displaced a patient’s mood is, the more intense levels of this psychogenic pain is felt (BINZER et al., 2003). Moreover, when comparing the intensity of psychogenic pain to physically stimulated pain, Binzer and colleagues (2003) found that there was no difference in perceived intensity. Patients could not differentiate between the psycho-driven pain and the stimulus-driven pain. This may suggest that our perception can so flawlessly reproduce pain that, even when confronted with a stimulus, the two pain types are nearly indistinguishable. This, however, does not go to say that research has found a lack of physiological abnormalities in those diagnosed with psychogenic pain. When considering the biological factors, those with chronic psychogenic pain display significantly higher levels of endorphins in the cerebrospinal fluid than healthy, unaffected individuals (ALMAY, 1978). Almay (1978) concluded that it is CSF endorphin levels that reflect the central processes of psychogenic pain disorders. It was proposed that a hyper-state of these endorphins may elicit the pain response. Taking both of these perspectives in to account, these disorders offer fair insight into the relationship between nociception and pain perception. It is evident that a physical abnormality, such as torn fibers or increased cerebrospinal fluid endorphins, can lead to a disorder in pain perception. Conversely, it may be possible that a disorder in mood (the limbic system, a player mentioned earlier) or perception can also affect the activation of damaged nociceptors (ALMAY, 1978; JULIUS, 1954). An abnormality in one system has the ability to affect the other and vice versa, in both cases. In conclusion, when exploring the human experience of pain, it is crucial to consider both nociception and the perception of pain as a whole, continuous process. These steps are separate, but feed into one another while also acting on one another. Furthermore, when considering the perception of pain, it is
important to take into account the effects that the stimulus and concurrent transmission of signals found in nociception has on the resulting experience. It is also important to take into account the levels of top-down processing seen in pain perception and nociception. Psychological aspects, such as fear and the limbic influences transcribed by the thalamus and hypothalamus, can affect the transmission of signals throughout the system. These effects can be analgesic in nature, or detrimental, as witnessed in disorders and diseases. Disorders, such as chronic psychogenic pain and phantom limb syndrome, offer support for a top-down theory of reception and perception. By studying these diseases, we can gain a new level of knowledge as to how this processing occurs, as well as an insight into the ratio of physical to psychological contributors. Further studies of the connectedness within the pain system are very necessary if we wish to produce successful analgesic treatments.

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