The Sensitization Model to Explain How Chronic Pain Exists Without Tissue Damage

Background 

In the event of acute, nociceptive pain, nociceptors are stimulated due to a cellular disruption or trauma. The extent and duration of nociception depends on the nature and size of the damage (Baron, 2006). This acute pain has a clear physiologic purpose; it forces patients to decrease activities and to protect the painful body part to promote tissue healing.

After repetitive activation of nociceptors, specific neurons within the spinal cord (wide dynamic range [WDR] neurons) take on a higher degree of readiness and become sensitized (Woolf & Salter, 2000). Influenced by pain-mediating substances, such as glutamate and substance P, these WDR neurons are more susceptible to input from other neurons and thus become hyperexcitable. This increased excitability is induced by alterations of the cell membrane, e.g., via N-methyl-D-aspartate (NMDA) receptor activation, as well as functional changes within the neuron itself. As a consequence of the increased excitability, stimulation of the affected body part—which would not be painful under normal circumstances—is now capable of evoking pain. This sensitization process causes decreased pain thresholds, which means that pain can be felt in response to stimuli that are not normally painful (Torebjork, Lundberg, & LaMotte, 1992; Woolf & Salter, 2002). The phenomenon of sensitization may apply to touch (allodynia) as well as to movement of trunk or limbs as in patients with chronic pain (Banic et al., 2004, Kasch et al., 2005). This process of sensitization is reversible and is called modulation (Woolf & Salter, 2000). Under normal circumstances, sensitization disappears when the anatomic defect or tissue damage has healed and nociception has ceased. However, in chronic pain patients, sensitization remains present after nociception has resolved (LaMotte et al., 1991, Koltzenburg et al., 1994, Kilo et al., 1994).

Sensitization and Chronic Pain 

After long-lasting nociceptive stimulation, primary afferents that terminate within the spinal cord begin to sprout to form new connections between neurons. In addition, inhibitory interneurons die as a consequence of excessive activation of NMDA receptors. Through these new connections and the death of inhibitory interneurons, pain signals are augmented and nonnociceptive signals from the periphery may now be misinterpreted as pain. These changes represent an irreversible structural reorganization of the neural network within the dorsal horn. This modification of connectivity may be an important explanation for the intractable nature of chronic pain (Woolf & Salter, 2000).

A pressing question is why sensitization (modulation) disappears in most patients after injury has healed, but does not in a minority of the patients. One explanation is the extent of nociception that was originally present as a result of an extensive anatomic defect or tissue damage. Severe and long-lasting nociception may cause more profound and irreversible sensitization than relatively minor injury (LaMotte, 1991). Furthermore, genetic factors may also be of importance, suggesting that some people tend to sensitize more vigorously than others (Wang et al., 2002, Zubieta et al., 2003). Finally, psychologic and behavioral aspects play an important role in the maintenance of sensitization (Gracely et al., 2004).

Neuroimaging techniques, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), have yielded better understanding of the cerebral processing of pain and pain stimuli. The limbic system, particularly the anterior cingulate cortex (ACC), is activated extensively in patients with chronic pain, reflecting a considerable contribution of affective-motivational aspects in the experience of this pain (Davis, 2000, Hsieh et al., 1995, Kurata, 2002, Peyron et al., 2000). Furthermore, increased brain activity is frequently observed in the prefrontal cortex (PFC), a brain area associated with the cognitive-evaluative and memory aspects of pain (Apkarian et al., 2005, Moisset and Bouhassira, 2007). Anxiety, depression, dissatisfaction, catastrophizing, and anger are psychologic factors leading to a greater experience of pain through an altered activation of limbic structures. The relation between psychologic factors and the occurrence and persistence of chronic pain, is in agreement with findings in psychologic studies in patients with chronic pain (Turk & Okifuji, 2002).

The way that these psychologic and behavioral factors cause or maintain sensitization in the nervous system is not completely clear. With fMRI, Ploghaus et al. (2001) showed, that anxiety-induced pain exacerbation was caused by cerebral activation, not only in the ACC, a brain area that is well known for its involvement in the emotional aspects of pain, but also in the hippocampus. These findings are consistent with the Gray-McNaughton theory of pain modulation, which postulates that the hippocampal formation sends pain-amplifying signals to limbic structures (e.g., the ACC) in case of aversive events such as pain. This process ensures that the subject's behavior is biased toward escaping the aversive event (Gray & McNaughton, 2000).

A network of descending pathways originates in the brainstem and influences the excitability of neurons in the dorsal horn in the spinal cord. The network of the descending pathways is under direct and indirect control from various regions of the cerebral cortex, such as the PFC, the ACC, the insula, and large areas of the frontal, temporal, and parietal cortices (Baron, 2006, Millan, 2002, Petrovic et al., 2002). These brain areas are also known to be involved in the processing of anxiety, attention, and cognition, strongly suggesting a relationship between psychologic factors and the degree of spinal sensitization (Peyron et al., 2000). The PFC is also involved in the modulation of pain signals through its direct influence on midbrain and brainstem structures, which may represent one of the pathways of placebo-mediated antinociception (Wager et al., 2004). Others have demonstrated that activation of the rostral ACC is also associated with placebo analgesia (Petrovic et al., 2002).

An illustration of the magnitude of this descending influence on pain, is the soldier who does not experience any pain in the heat of the battle, even though he is badly injured. In contrast, extreme pain can be felt following minor injury when the subject is anxious or has had previous negative experiences with the same sort of pain. Altogether, cognitive-emotional dimensions are capable of modulating pain signals—and subsequently pain intensity—in both positive and negative ways. Patients with chronic pain share several features, i.e., spinal sensitization and failing inhibition of the descending pathways. Explaining to the patient that the pain is not the result of anatomic defects or tissue damage that should be detected and cured, but that sensitization has taken place, appears to be a logical first step toward breaking the vicious circle of chronic pain.

Central sensitization is a likely explanation for a patient's chronic pain when certain conditions are met. First, after adequate diagnostic research, the presence of nociception should be unlikely. Second, nonpainful stimulation, such as touching (allodynia) or moving the affected parts of the body leads to the report of pain, and painful stimulation may lead to an increased perception of pain (hyperalgesia) (Merskey & Bogduk, 1994).

Explaining Chronic Pain 

How can the sensitization model be used in the clinical practice, and which competences are required from a nurse to use the model? As stated above, an anatomic defect or tissue damage as cause for the pain should have been excluded, and signs of sensitization (hyperalgesia, allodynia) of any kind must be recognized. In patients with chronic pain, any diagnosis should be based on a biopsychosocial assessment.

The biopsychosocial model was originally described by Engel (1980), who highlighted the inadequacies of a biomedical model only and advocated the endorsement of a biopsychosocial approach. This approach is mandatory to integrate physical, psychologic, behavioral, and environmental factors to understand why sensitization is maintained. In individual patients, the identification of psychologic, behavioral, and/or social problems can be related to the existence and persistence of sensitization. In this way, the sensitization model can motivate patients for a more behavioral of psychologically orientated treatment. Importantly, to use only the explanation of a sensitized nervous system may create just another somatic explanation for chronic pain and will probably not lead to better coping mechanisms in patients with chronic pain. To provide adequate education, nurses need to have knowledge of the neurophysiology of pain, must be familiar with the use of the biopsychosocial model, and, last but not least, appropriate communication skills are necessary.

The sensitization model (Appendix 1) offers an opportunity to explain pain itself as a somatic process, with underlying biopsychosocial factors contributing to the maintenance of the sensitization. Agreement on the causes and maintaining factors of the pain is essential before entering a treatment.

Discussion 

The use of the sensitization model to explain chronic pain has not been evaluated in clinical studies, but the use and the effectiveness of similar neurophysiologic explanation models have. Moseley, Nicholas, & Hodges (2004) described a randomized controlled trial in which positive results in the education group were found on pain attitudes, catastrophizing, and physical performances. In nursing science, there is a wealth of research in patient education; the sensitization model may be useful to be implemented in the education programs for patients with chronic pain.

The complex concept of sensitization can be best explained using a metaphor. A suitable metaphor for chronic pain is the burglar alarm. A metaphor to explain chronic ongoing pain, e.g., fibromyalgia or headache, can be a thermostat: “The thermostat is set too low, which leads to constant overheating of the house.” Several metaphors can be used; a metaphor must fit the patient, e.g., a metaphor related to someone's work or hobbies, but it must also fit the capability of the nurses and their experience in using such a model.

Conclusions 

Many patients with chronic pain share the same pathophysiologic mechanisms: sensitization of the nervous system. For patients, it is important to get an explanation for their chronic pain. The sensitization model provides nurses with an opportunity to explain pain as having a physical cause related to changes in the nervous system. In this explanation model, neurophysiologic changes are of equal importance as behavioral, psychologic, and social mechanisms. Acceptance of the sensitization model may increase a patient's motivation for treatment and improve the interaction between chronic pain patients and nurses.