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11 Articles in Volume 11, Issue #8
Pain Following Combat Trauma In the 21st Century: A New Look at an Old Problem
Part 2: Fibromyalgia: Practical Approaches To Diagnosis and Treatment
Advances in Regenerative Medicine: High-density Platelet-rich Plasma and Stem Cell Prolotherapy For Musculoskeletal Pain
Implant Technologies for Severe Pain: Why, When, and the Outcomes
Value of EMG in Patients With Non-Migrainous, Persistent Head Pain
Drug Interactions Among HIV Patients Receiving Concurrent Antiretroviral and Pain Therapy
Etiology of Chronic Pain and Mental Illness: The Biopsychosocial Component
Insights Into Patients’ Views About Topical Opioids: Observations From a Small Clinical Study
Teenage Boy With Multiple Pain Disorders
The Bench Delivers and It Matters
Renewing Opioid Prescriptions Over the Phone

Etiology of Chronic Pain and Mental Illness: The Biopsychosocial Component

Part 1 of a three-part series examining the comorbidity of chronic pain and mental health disorders.
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It has been well established that there are high levels of comorbidity between chronic pain conditions and mental health disorders.1,2 Moreover, psychiatric conditions, such as depression, anxiety, substance abuse, personality disorders, and post-traumatic stress disorder (PTSD), occur more frequently in patients with chronic pain than in the general population.3-11 Many clinical researchers have proposed explanations for the co-occurrence of pain conditions and mental health disorders. The strongest evidence has been found in support of biopsychosocial models, which simultaneously incorporate both biological and psychosocial components. This article will address the biological process involved in mental illness and pain. Future articles in the series will address assessment of mental illness and treatment of the comorbid patient.

Neurotransmitter Activity
One of the most widely studied mechanisms for comorbid pain and mental health disorders is the effect of neurotransmitters. Many of the same neurotransmitters are implicated in both pain and psychosocial disorders, including serotonin, norepinephrine, and dopamine.12-15 Low levels of serotonin have been associated with migraine, cluster, and analgesic abuse headaches, as well as fibromyalgia (FM).16-18 Antidepressants that inhibit serotonin reuptake have been shown to improve symptoms in temporomandibular disorders (TMD), tension-type headaches, FM, and certain neuropathic pain conditions.19-22 Klauenberg et al found that in an experimental pain task, depressed patients failed to inhibit the summation of pain signals.23 The investigators hypothesized that dysfunction of the serotonin system may be responsible for the failure to modulate sensory inputs, leading to greater vulnerability to chronic pain conditions. Numerous other clinical trials have also been conducted that revealed a correlation between decreased serotonin functioning and lowered pain thresholds.17,24,25

Neuroendocrine Function
The relationship of the neuroendocrine system, especially the hypothalamic–pituitary–adrenal (HPA) axis, to both psychosocial and pain disorders has been well established. The HPA axis is the body’s primary stress pathway, and it is activated by corticotropin-releasing factors from the hypothalamus, which stimulate the release of cortisol from the adrenal glands. Cortisol modulates the metabolism of serotonin, norepinephrine, and dopamine.26 Melzack proposed that cortisol might have a cumulative destructive effect on bone, muscle, and neural tissue.27 The dysregulation of cortisol has been associated with a number of pain conditions, such as TMD, FM, and chronic daily headaches.18,28,29 Additionally, mental health disorders, such as anxiety, depression, PTSD, and substance abuse, are associated with abnormal HPA axis functioning.15,30-32 Several clinical studies have concluded that evidence of cortisol dysfunction is particularly strong in patients with comorbid pain conditions and major depressive disorders (MDD).33-35

fMRI Brain Imaging
Functional magnetic resonance imaging (fMRI) technology can provide a real-time view of brain area activity. Few studies have examined the combination of chronic pain and mental health disorders; however, several brain areas have been identified as important in the processing of both pain and mood state. Reduced cerebral blood flow to the thalamus, a region of the brain responsible for relaying signals to the cortex, has been found in both chronic pain and depression.15,36 Similarly, the dorsal anterior cingulate cortex, anterior insula, and amygdala are involved in both depression and the emotional appraisal of painful sensations.35 Giesecke et al found that the presence of MDD and chronic pain was associated with activation of the amygdala and anterior insula (brain areas that process the emotional and motivational aspects of pain) in response to experimental pain.14 Numerous researchers have proposed that both chronic pain and MDD involve abnormal anticipatory processing and hypervigilance.14,37,38

Peripheral Pain-Processing Mechanisms
Differences in peripheral pain processing have been documented in patients with comorbid pain and mental health disorders.23,39,40 Klauenberg et al found that patients with both chronic pain and MDD failed to inhibit pain under conditions of repetitive stimulation, with repetitive noxious stimuli leading to a decompensation of the patients’ pain suppression mechanisms.23

Several psychosocial mechanisms to account for the comorbidity of pain and mental health disorders have been proposed. Learning and conditioning mechanisms have been implicated in both chronic pain and mental health disorders.1,14,35 Giesecke et al proposed that the association of sadness with pain was common to both chronic pain and depression, as was learned helplessness, a condition in which a person who has been unable to control a noxious stimulus eventually stops trying and responds with depressive symptomatology.14

Cognitive mechanisms also have shown an association with both pain and psychosocial conditions. Catastrophizing, which refers to responding to negative events with overwhelming helplessness and by seriously overestimating the likely negative consequences, is associated with pain, depression, and anxiety.35 Several researchers have found support for the hypothesis that catastrophizing and other negative appraisals of pain alter the effects of depression on the affective and evaluative experience of pain.40,41 Personality traits also have been linked to both pain and mental health disorders. Neuroticism, a tendency to experience negative emotional states, has been associated with psychosocial disorders, including PTSD, anxiety, and depression, as well as pain conditions such as TMD, low back pain (LBP), and migraine headache.42-46 Another personality trait linked to chronic pain and psychosocial disorders is anxiety sensitivity, which increases risk for panic and anxiety disorders and is associated with chronic musculoskeletal pain and recurrent headache.47-50

Other psychosocial factors that influence chronic pain and psychopathology include self-regulation and coping strategies. Self-regulation often is lacking in personality disorders.35,51 Sansone et al proposed that in some patients with borderline personality disorders, chronic pain is related to a failure to regulate the experience of pain and the emotional reactions associated with pain.51 Coping strategies that are passive (such as hoping) or avoidant (such as reducing activity or isolation) also are associated with comorbid chronic pain and depression.52

Last updated on: December 15, 2014