Chapter 16
The multidimensional nature of pain
Introduction
This chapter describes the fundamental nature of pain and the multitude of mechanisms that are associated with patients’ perception of pain.
Definition of pain
Pain is defined as “an unpleasant and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (40). It is a complex experience of a multidimensional nature, and is always subjective and associated with emotional and cognitive factors. Today it is widely accepted that pain is much more than the mere activity in the nociceptor and nociceptive pathways of the nervous system elicited by a noxious stimulus. Pain is invariably a psychological state and can be reported in the absence of tissue damage or any likely pathophysiological causes.
The neuromatrix theory
According to Melzack (55), pain is a multidimensional experience produced by characteristic “neurosignature” patterns of nerve impulses generated by a widely distributed neural network in the brain. This neurosignature for pain experience is determined by the synaptic architecture of the neuromatrix, which is shaped by both genetic and sensory influences and modulated by sensory inputs and cognitive events, such as psychological stress. Disruption of the neuromatrix homeostasis by a stressor, either physical or psychological, activates programs of neural, hormonal and behavioral activity aimed at restoring homeostasis. Occasionally, when failure in the homeostasis regulation occurs, the neuromatrix produces the dysfunctional conditions that may cause chronic pain conditions, which are often resistant to treatment procedures developed for acute pain conditions. The particular activated programs are selected from a genetically determined repertoire of programs that have been modified by events, such as earlier exposure to stress, and are influenced by the extent and severity of the perceived stress.
The significance of the neuromatrix theory is that it guides us away from the concept of pain as just a simple sensation produced by injury, inflammation or other tissue pathology, and promotes the concept as a multidimensional experience shaped by multiple influences, e.g. stress, anxiety, expectation, focus of attention, gender and culture (Core concept 16.1).
Acute versus chronic pain
Although this overall view of pain as a multidimensional experience is attractive and prudent, it should be emphasized that there is an immense difference between acute and chronic types of pain. Acute pain is necessary for the organism to survive. It serves as a warning or alert sign for appropriate action to be taken and healing and restoration of function to occur. Chronic pain does not serve a biological purpose and is often closely associated with an impaired quality of life, distress and a negative impact on personal, social and work relationships. Pain associated with acute tissue damage, disease or intervention can be viewed as a symptom, whereas chronic pain, in addition to the psychological aspects, may resemble neurodegenerative conditions and can be classified as a disease in its own right. The arbitrary time point of 6 months is a realistic way to distinguish between acute and chronic pain. However, it is more reasonable to talk about chronic or persistent pain, if the pain lasts longer than expected after a normal healing period.
Neurobiological factors affecting the pain experience
Overview of pain mechanisms
In the field of pain, there is ongoing discussion as to what extent is it possible to classify pain according to the current knowledge of the mechanisms involved (71). The proposed mechanism-based classification has four main categories (Core concept 16.2).
Transient or nociceptive pain may be the easiest type of pain to understand, although recent advances in molecular biology have shown the complex nature of even “simple” processing of pain. The nociceptor is the basic receptor on primary afferent nerve fibers innervating the orofacial tissues. On the peripheral terminals, a multitude of transducing receptors and ion channels have been identified, e.g. acid-sensing ion channels (ASIC), a family of transient receptor potentials receptors (TRPV1-8), P2X3 receptors. These receptors are unique in that they detect and respond to specific high-intensity stimuli (heat, cold, mechanical, chemical stimuli), potentially associated with tissue damage and therefore serve as a warning system. It has been suggested that there is a nociceptor specialization (64) in that sophisticated “sensors” in the peripheral tissue, including tooth pulp and periodontium, can be activated unintentionally during numerous dental procedures (procedural types of pain). Besides the psychological aspects (described below), there is a strong neurobiological rationale to prevent pain experience during dental procedures, including endodontics, by the appropriate use of local anesthetics.
- Transient (nociceptive) pain
- Tissue injury (inflammatory) pain
- Nervous system injury (neuropathic) pain
- Functional pain
Overt tissue damage, e.g. by trauma and surgical procedures, is commonly associated with pain. In most cases pain in this context can be viewed as part of the classical cardinal signs of inflammation: dolor (pain), tumor (swelling), rubor (redness), calor (heat sensation) and loss of function. However, significant progress has been made in terms of understanding the neurobiological changes in the nociceptive system in these conditions. One important aspect is that the nociceptor can initiate spontaneous activity without a peripheral stimulus leading to spontaneous pain (64). Another is “sensitization”, where the threshold for activation of the nociceptor is reduced and the responses are longer and stronger (39). Additionally, previously silent nociceptors can be awakened and further contribute to pain (see also Chapter 3). There is also evidence that functional shifts occur in the number and activity of receptors and ion channels on the nociceptor, e.g. receptors for nerve growth factor (NGF), bradykinin (BK) and prostaglandins (PGE) are activated, increasing membrane excitability. Second-order neurons in the trigeminal sensory nucleus complex react to the increased trafficking of action potentials from the nociceptor and sensitization of the neurons in the central nervous system occurs (64). A multitude of biological responses takes place involving phosphorylation of NMDA receptors and activation of neurokinin and neurotrophic receptors (71). The understanding of the intracellular pathways is fairly advanced as they include alterations in gene expression of neurotransmitters and neuromodulators. Although the phenomenon of peripheral and central sensitization can develop within minutes, usually these processes are completely reversible in conditions with inflammatory types of pain.
Nervous system injury pain (neuropathic pain) can occur if the peripheral nerve fibers are damaged (71), for example, due to surgery (third molar surgery, orthognathic surgery on the maxilla and mandible, insertion of implants, etc.) or to disease, such as postherpetic neuralgia or diabetic neuropathy and even pulpitis. Neuropathic pain may also develop following injury to the central somatosensory system, e.g. by stroke, multiple sclerosis and spinal cord injuries. The consequences of these lesions are spontaneous pain and hypersensitivity to painful stimuli (64). Thus, the primary afferent nerve fiber can initiate spontaneous discharges due to ectopic neural activity near the peripheral nerve lesion. Phenotypic changes and alterations in the expression and distribution of ion channels can occur, which contribute to an increase in membrane excitability (71). Thus, it is easy to understand that sensitized nerve fibers play an important role in neuropathic pain.
Unfortunately, the neurobiological mechanisms underlying neuropathic pain are irreversible and resistant to current pharmacological therapy. The central nervous system also plays a significant role in these conditions. For example, one response at the second-order neuron is the loss of normal inhibitory mechanisms mediated by the neurotransmitter GABA and glycine (71). There is evidence that 1 week after nerve injury, signs of apoptosis appear in the dorsal horn neurons. Therefore, there is strong interest in developing therapies that will prevent activation of such changes to avoid disturbances in the delicate balance between inhibitory and excitatory pathways (Core concept 16.3).
The concept of functional pain is an evolving one. There appears to be nothing wrong in the peripheral tissues, but it is believed that for some unknown reasons there is an abnormal amplification and processing of peripheral stimuli in the central parts of the somatosensory system (71). Fibromyalgia, irritable bowel syndrome and possibly tension-type headaches are examples of this disorder. In contrast to the inflammatory and neuropathic types of pain in which there is local hyper-sensitivity to painful stimuli, in the functional types of pain this hypersensitivity is widespread and generalized. Comprehensive pain analysis and careful elucidation of the psychosocial aspects should be used to assess the somatosensory function in the painful and non-painful parts of the body (15). Simple tests of somatosensory function can easily be performed in the dental office and more elaborate tests (quantitative sensory tests – QST) are normally available at university clinics (64).
Distinguishing neuropathic pain from other pain conditions
From a management perspective it will be important to differentiate between the different types of pain. Neuropathic pain is a distinct condition and requires a careful clinical examination combined with confirmatory tests. To establish a definite diagnosis the following are required:
- occurrence of pain with a distinct neuroanatomically plausible distribution;
- a history suggestive of a prior relevant lesion or disease affecting the peripheral or central somatosensory system;
- demonstration of the distinct neuroanatomical distribution by at least one confirmatory test (e.g. QST); and
- demonstration of the relevant lesion or disease by at least one confirmatory test (e.g. magnetic resonance imaging or recording of electrophysiological abnormalities).
Nevertheless, there will still be gray areas where the clinical manifestations of a nociceptive type of tooth pain may overlap with a neuropathic or functional type of pain. A diagnostic filter starting with exclusion of transient, nociceptive pain and neuropathic pain will lead to relatively few patients ending up in the functional pain category (5).
Pain genetics
In the field of pain, one of the most intriguing discoveries is the association between certain types of genes and pain expression. It is common knowledge from the dental office that some patients are more susceptible to stimulation of the orofacial region, i.e. patients reporting very high levels of pain even in the absence of a strong nociceptive input via the primary afferent nerve fibers. And vice versa, there are patients who are much more “pain resistant”. Notwithstanding the significance of the psychosocial aspects of pain, several genetic markers of “pain-sensitive” and “pain-resistant” patients have recently been identified. One of these markers is based on the polymorphism of the cathecol-O-methyl-transferase (COMT) gene. COMT is an enzyme that metabolizes catecholamines and is critically involved in pain perception, cognitive function and affective mood with a strong impact on the efficacy of the endogenous pain modulatory systems (75). Polymorphism of the adrenergic-receptor-beta-2 gene has been linked with differences in pain sensitivity. It is likely that there are many more gene candidates that may contribute to individual differences in the expression of pain and to analgesia. The significance of this new emerging knowledge is that there is a key to open some of the “black boxes” in understanding why pain is experienced differently.
Relevance for tooth-related pain
Dentists are usually good at understanding acute pain related to teeth. For most patients, stimulation of the tooth pulp, either by accident (trauma), drilling (procedural), caries (disease) or endodontic treatment, will be associated with a painful experience. There are numerous techniques that can be used (the psychological aspects will be covered below) to prevent or relieve transient and inflammatory pain. However, neuropathic and functional types of pain related to the teeth are less well understood and the underlying mechanisms are different (described above). Additionally, the nociceptive pathways are influenced by sex and sex hormones and are genetically controlled. Therefore, it is important for the dentist to establish the type of tooth-related pain suffered by the patient and to remember that neurobiological factors also cause the clinical presentation of pain.
Psychological factors affecting the pain experience
Affective factors
Impact of stress, fear and anxiety
It is widely believed that anxiety is associated with increased pain report (14). A tense and anxious patient is more inclined to report pain during treatment than a relaxed one, since anxiety creates expectancy for future pain. An anxious patient who arrives for treatment with former pain memory is likely to expect pain during treatment. This causes the patient to selectively filter any information given prior to treatment and to focus on stimuli which can resemble, or be associated with, pain. For example, the slightest pressure on the tooth can be interpreted as pain and initiate a pain reaction. Arousal caused by anxiety may also lead to increased sympathetic activity and muscle tension, which may cause additional pain.
Dental anxiety is a prevalent obstacle which affects human behavior in the dental setting (24). Among all dental situations, oral surgical procedures and endodontic therapies cause the highest levels of stress and anxiety (9, 26). According to Arntz et al. (4), anxiety experienced during dental treatment plays a role in maintaining the problem of inaccurate expectations of fear of treatment. For example, pain experienced by patients in oral surgery is best predicted by their anxiety at each time point (28).
There is a high probability that patients who arrive for endodontic treatment are anxious and expect to experience some degree of pain during treatment. This can cause patients to report pain during treatment even when there is no rationale (e.g. drilling in a tooth with non-vital pulp). Occasionally, proper local anesthesia is extremely difficult to achieve and the patient continues to complain of pain in spite of several attempts. These situations are closely associated with the patient’s fear of dental treatment (41) (Key literature 16.1).
By definition, pain is always subjective. In the clinic, there is no way to distinguish between pain due to psychological reasons and pain originating from actual tissue stimulation. In both, it is regarded and reported by the patient as pain and should be accepted and referred to as such.
Impact of mood
Mood, especially depression, influences pain perception and pain tolerance. There is a close relationship between chronic pain states and depression (63). It has been hypothesized that chronic pain and depression are closely related owing to similar neurochemical mechanisms involved in both disorders. Another reason for the depressed mood is the way in which chronic pain interferes with important areas of functioning, e.g. decline in social activities and social rewards (61).
Mood can also affect pain perception in short-term acute pain situations, e.g. dental treatment. For example, acute pain perception can be affected by a film-induced mood condition (69). Subjects who watched a humorous film prior to a painful stimulus tolerated the pain challenge better than other subjects. This suggests that psychological approaches could have a significant effect on the sensory dimensions of pain and that pain tolerance in patients can be substantially increased with simple measures, including the showing of humorous films in the waiting room.
Cognitive factors
One of the most potent forms of stress is pain. The pain experience includes actual confrontation with harm, which can be physical (e.g. injury), psychological (e.g. loss of control) or interpersonal (e.g. shame). As such, it is affected by both the potency of the stimulus and the individual’s ability to cope with the stressful event (60).
Attention versus distraction
Almost any situation that attracts a sufficient degree of intense, prolonged attention (e.g. sports, battle) can provide conditions for other stimulation to go unnoticed, including wounds that would cause considerable suffering under normal circumstances. Broadly defined, distraction is directing one’s attention from the sensations or emotional reactions produced by a noxious stimulus. Generally, distraction reduces pain compared to undistracted conditions (54).
Dentists can apply distraction techniques while treating their patients, e.g. using background music and talking to the patient. Several advanced methods have been described as effective in the dental clinic, such as mounting a television monitor near the ceiling, or asking the patient to play a video game “against the house” (13). While distraction techniques that require attentional capacity are effective in reducing pain-related distress, even the simplest distraction technique is beneficial in reducing the patient’s stress and pain perception. Studies have shown that the use of video glasses during dental scaling and restorations had no or only minor effects on the perceived pain. However, a striking finding was that most patients would still like to use the video glasses and reported a positive effect of this “distraction” technique (7).
Control
Control affects stress, coping mechanisms and reaction to pain (50). People in pain usually search for information to give meaning to the experience. Therefore, anxiety and pain levels associated with dental procedures can be reduced by providing the patient with updated information on the forthcoming procedures and the description of the likely sensations. For example, patients provided with detailed information on how N2O analgesia works showed higher pain tolerance thresholds to tooth pulp stimulation than patients without this information (22). Since the fear of uncontrolled, sudden, acute pain is a primary concern for most patients (48), continuous information regarding ongoing procedures is an important way to provide patients with some sense of control or involvement (Core concept 16.4).
Pain beliefs and expectations
Reaction to a stimulus, whether acute or chronic, is always affected by its meaning to the individual. For example, the patient can interpret an episode of an unexpected, unexplained pain during treatment as a sign of the dentist’s insufficient professional skills. This, in turn, can develop mistrust in the dentist and cause the patient to interpret any further minor stimulus as a threat and evoke a pain reaction. Conversely, when mutual trust exists, the patient’s belief in the necessity of the treatment makes these incidences bearable and less traumatic.
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