By Brittany Smolarski
Perplexing to physicians is the finding that patients with the same type and degree of injury may complain of vastly different levels of pain exacerbation, including pain severity, debilitation, life effects, and relative control. Evidence suggests that this phenomenon is due to psychosocial factors that are compounded by patient’s unrelenting symptoms, an insufficient availability of impactful treatments, and the extensive effects of such pain on physical function (Moriarty, McGuire, & Finn, 2011). These factors affect cognition of pain, thereby impacting pain exacerbation and initiating neurobiochemical changes throughout the Central Nervous System (CNS) that further compound and reinforce pain conditions.
Because pain is experienced not only as a threat to the healthy bodily state, but also to one’s current and future well-being, it is not surprising that chronic pain and emotional state are directly linked. The most common emotions associated with chronic pain are depression, anger, fear, and anxiety (Pincus, 2006). Patient appraisal of perceived disability, along with judgment of control over pain, mediates the pain-depression relationship. Patients who exhibit an internal locus of control and believe they are able to effectively manage their pain demonstrate less pain exacerbation and disability than those who feel more helpless (Price, 2000; Turk et al., 2007; Pincus, 2006). Anger caused by unrelenting symptoms, treatment inadequacy, and cost of treatment can also contribute to dysphoric patient mood. Additionally, anticipation of pain creates fear-based anxiety and pain catastrophizing that results in hypervigilance, exaggerated sensitivity to pain symptoms, and avoidance behaviors. Although initially protective, these behaviors become maladaptive when they cause decreased physical activity, increased fear and hypersensitivity, and ultimately increased pain exacerbation (Turk et al., 2007).
We can call the impact of cognition on physical pain state “mind over matter,” as it is reflected not only in a patient’s behavior and self-report, but also in their objective physiological measures (Pincus, 2006). Although the sensory and psychosocial aspects of pain are separable, it is now evident that the neural pathways that contribute to both of these systems are linked. Pathways from nociceptive Lamina-1 and NK-1 spinal neurons can activate limbic systems (emotional areas) of the brain. Limbic system activation can then trigger descending control pathways through serotonin (5-HT) signaling from the rostroventral medulla, ultimately altering coding and downstream perception of harmless versus harmful stimuli (Suzuki, Rygh, & Dickenson, 2004). Thus, there is a direct link between patient emotional state and level of pain. Through this link, significant emotional disturbance can initiate widespread neurobiochemical changes that enhance pain exacerbation (Dickenson, 2007).
In uninjured nerves, a peripheral stimulus (PS) (i.e. stubbing a toe) is required to activate peripheral nociceptors (PN’s). After nerve injury, such as that experienced by patients with chronic pain, action potentials spontaneously arise in the absence of a PS, stimulating damaged neurons and their surrounding uninjured neighbors. This is caused by the upregulation of sodium channels and downregulation of potassium channels along the membrane of both damaged and neighboring neurons, resulting in a decreased activation energy, and thereby easier stimulation, along the nerve. The injured nerve also demonstrates increased electrical input to the spinal cord due to upregulation of calcium channel regulatory subunits. This causes increased neurotransmitter (NT) release into the spinal cord to activate sensory nerve transmission to the brain. These significant alterations to the electrical properties of the nervous system cause central sensitization, which is the amplified neural signaling within the CNS that results in hypersensitivity and hyperalgesia (Dickenson, 2007; Colvin & Power, 2005).
Chronic pain perception is also linked to specific changes in brain chemistry. Evidence shows that awareness of chronic pain occurs in the prefrontal cortex, which then engages a network of brain regions to communicate this information. Brain chemistry changes associated with chronic pain begin in the prefrontal cortex and spread throughout these networks, demonstrating a relationship between neurochemistry and pain perception. The balance between excitatory and inhibitory NTs is altered following nerve injury. Breakdown of N-acetyl aspartate in the prefrontal cortex generates aspartate, an excitatory amino acid NT. This increased excitatory NT presence induces recruitment of N-methyl-D-aspartate (NMDA) receptors, leading to increased neuronal activation that can cause altered gene expression, protein synthesis, and long term potentiation that exaggerates neuronal responses. Lastly, levels of inhibitory NT γ-aminobutyric acid (GABA) are decreased bilaterally in the dorsal horn, such that even small pain signals are no longer inhibited (Colvin & Power, 2005; Grachev, Fredrickson, & Apkarian, 2000).
Interestingly, chronic pain can seemingly spread and begin to affect uninjured areas of the body. This is largely due to reorganization of the primary somatosensory cortex caused by hyperactive pain signaling. Each bodily region corresponds to a specific region along the sensory cortex. Research has shown that injury to particular nerves may result in expansion of the sensory area receiving that aberrant nerve signaling into adjacent cortical areas (Elbert et al., 1994). In a study of patients with chronic lower back pain, patients demonstrated that cortical representation of the back had shifted medially, indicating an expansion of the back sensory area into neighboring leg and foot areas. This finding was later corroborated by Flor et al.’s (1997) report that showed a strong correlation between the shift of cortical representation with magnitude and location of perceived “phantom” pain.
Prolonged exposure to stress caused by chronic pain also has disastrous systemic effects on the body (Turk et al., 2007). Stress-induced hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis results in increased cortisol (stress-hormone) levels, ultimately causing glucocorticoid resistance that augments inflammation and increases the presence of pro-inflammatory cytokines to induce neurodegeneration. In addition, aberrant diurnal cortisol level fluctuations severely disrupt normal sleep cycling, impairing the production of important proteins involved in neuroplasticity. The stress and HPA activation caused by chronic pain also compromises gut circulation, digestion, and the microbiome, leading to excessive inflammation and Enteric Nervous System activation (Bongiorno, 2012). Gut malabsorption, inflammation, and stress-induced alterations in microbiota composition have correspondingly been shown to exacerbate anxious and depressive behaviors, likely because of the microbiome’s role in regulation of 5-HT synthesis and signaling (Foster & Neufeld, 2013; O’Mahony et al., 2015).
The significant nervous system alterations caused by pain reveal the relationship between emotional state and cognitive-interpretive processes (Turk et al., 2007; Turk & Monarch, 1996). Cognitions of chronic pain and its associated emotions are clearly core determinants of whether a patient enters a positive or negative pain cycle, as they govern how the patient adapts psychosocially and responds neurobiochemically to their chronic pain. The mind over matter connection has been corroborated by research showing that patients who feel self-efficacious in managing their pain experience significantly less pain exacerbation (Price, 2000; Turk et al., 2007; Pincus, 2006). Thus, both the psychosocial and neurobiochemical aspects of chronic pain unquestionably portend the complexities of pain management. Accordingly, chronic pain patients must employ a holistic approach to treatment that addresses both mind and matter so as to most effectively abate pain exacerbation.
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