INTRODUCTION

Patients with chronic painful spine conditions are anxious, and for good reason. Uncertain about the cause and eventual outcome of their spine disease or spinal injury, they may worry about the consequences to their own and their families’ well being. Can they work and maintain their financial solvency? Will the stress of pain and disability interfere with their recreational activities and their important relationships such as families, coworkers, friends, and particularly spouses, including their ability to be sexually active and emotionally intimate? Will they become more depressed? Which of the many treatment options should they pursue and will they have access to the best treatment for their condition?

This situational anxiety often worsens pain or contributes to morbidity and poor treatment outcomes. Uncertainty in the healthcare system also contributes to patient anxiety, both directly and indirectly. Despite advances in diagnostic and therapeutic spine medicine, which creates hope and relief for many with spine pain, healthcare systems are notoriously unable to adequately manage chronic spine pain, for several reasons.

A central feature of any dysfunctional system is the uncertainty and anxiety of its constituents; just ask the investment business. As mentioned earlier, persons with spinal pain with or without its complications is uncertain about their own and their family’s future. The physician treating pain is uncertain as to how to proceed with treatment once initial treatment has failed and how to maintain a financially viable practice in the face of nonreimbursement of time-consuming office visits and phone calls from patients with chronic pain. The policy-makers and operatives of the governmental agencies and third parties funding the healthcare system, beset with competing interests and responsible for the economic viability of their portion of the healthcare system, are uncertain about the most effective strategies and policies. Their reflex is to discourage innovation in hopes of reducing expenditures. This chapter will review principles of managing the problem of fear and anxiety in patients with spinal pain in the context of this insecure and anxiety-provoking healthcare environment.

ORIGIN AND DEFINITION OF THE MODERN CONCEPT OF ANXIETY

The concept of anxiety as an emotional experience distinct from fear is a relatively modern notion with its origins in the works of Sigmund Freud. It is interesting historical trivia that the German word for fear, ‘angst’ was inappropriately translated in some of Freud’s work to the subtly different word, ‘anxiety.’¹ Although Freud made no distinction between fear and anxiety in his writings, this linguistic accident helped create a distinction between the concepts of fear and anxiety.¹ This distinction, especially in relation to chronic anxiety disorders, has held up to scientific scrutiny. Fear, broadly defined, is a complex emotional and physical response to an actual threat (i.e. response to a physical attack.) Anxiety, by contrast, is a complex emotional and physical response to a perceived threat (i.e. believing an attack is imminent). Both fear and its analog, anxiety, are responses to stress that, when functioning properly, are adaptive and necessary for survival. It is when the physical and emotional sequelae of fear and anxiety are excessive in relation to their context, or when they lead to a state of chronic incapacity and loss of function, that they become a cause for clinical concern. As outlined above, chronic pain creates many situations that may provoke fear or anxiety.

Acute fear in a perceived dangerous situation has the effect of modulating pain sensation to enable successful fight-or-flight reactions. In the patient with chronic pain, the role that fear and chronic anxiety has in the maintenance and exacerbation of their symptoms cannot be underestimated. The common physical symptoms of anxiety, such as muscular tension, hyperarousal, insomnia, palpitations, and poorly localized pain, often confound a patient’s primary medical or surgical pain complaint. Anxiety, through activation of the noradrenergic system in the locus coeruleus, has both peripheral and central effects on pain perception in persons with nociceptive, neuropathic and visceral pain conditions, as listed in Table 15.1. Add to this the psychological symptoms associated with anxiety (worry, apprehension, irritability, poor concentration, overinterpretation of symptoms) along with the effects of anxiety on illness behavior, including presentation of pain complaints and compliance with treatment regimens, and the complexity of treating a patient with chronic pain with acute or chronic anxiety becomes obvious.

Table 15.1 Effects of Anxiety on Pain Conditions and Disorders

Condition	Physiologic Effect of Anxiety	Consequences for Pain
Nociceptive pain	Sympathetic nervous system activation	Higher pain levels
	(1) lowering threshold for nociceptor activation

Increased sensitivity to pain stimuli Muscle spasm Neuropathic pain Sympathetic nervous system activation Acute activation of pain in response to stressful circumstances Increase in spontaneous neuronal firing with worsening pain Increase in spontaneous neuronal firing with worsening pain Visceral pain Sympathetic nervous system activation Stimulation of visceral plexuses with secondary pain effects such as activation of bowel in irritable bowel and bladder irritation in interstitial cystitis Central pain Activation of noradrenergic projections to brain centers of pain suffering and mood dyscontrol Reduced descending modulatory control of ascending pain signal.   Conditioned activation of pain suffering Interference with task-oriented concentration Reduced distraction-based modulation of pain

Before moving to a discussion of the treatments for acute and chronic anxiety, it is necessary to briefly describe in more detail the neuroanatomical and biological correlates of fear, anxiety, and pain so we may better understand how they are interrelated.

THE BIOLOGICAL BASIS OF FEAR AND ANXIETY

The biological and anatomical substrates of fear as a trigger for a fight-or-flight response are ancient. Countless behavioral experiments have established that nearly every species, from snails to humans, can develop a conditioned fear response to noxious stimulus.

By contrast, chronic anxiety, because of its anticipatory nature, requires a greater degree of biological processing capacity. Humans, with a near infinite capacity to perceive and anticipate threat, are exquisitely equipped to experience anxiety.

Figure 15.1 is a conceptual rendition of the basic neuroanatomical components of fear. The connections between these structures are much more complex than the pathways depicted in this illustration, but they provide a general idea of how these anatomical structures communicate and synthesize environmental, emotional, and learned stimuli. The spatial relationship of the brain regions depicted in this illustration is generally analogous to their location in the human brain.

Figure 15.1 highlights the crucial role the amygdala plays in the fear response. It is essentially the central processor of fear. The amygdala receives and transmits information from the external world (via the thalamus, ventral tegmental area, and reticular formation). It merges this information with our memory, senses, executive functions, endocrine and musculoskeletal systems (via the hippocampus, sensory/motor cortex, association cortex, hypothalamus and brainstem) to elicit a complex emotional and behavioral response.

In humans, the amygdala is thought to be essential for the recognition of threatening environmental cues and modulation of the emotional response to them. Neuroimaging experiments of normal human brains show that the amygdala is important in our ability to recognize and respond to threatening stimuli in the form of disturbing faces, gestures, and scenes that evoke fear.^2,3 This basic finding corresponds to the deficits observed in persons with surgical destruction of the amygdala and children with autism. In both cases, there is an enormous deficit in the individual’s ability to accurately identify and respond to fear-evoking stimuli.^4,5

Other experiments have suggested the amygdala also plays an important role in the development of chronic anxiety and pain. One study has found that activation of the basolateral nucleus of the amygdala causes the emotional experience of anxiety without a corresponding increase in heart rate (which is controlled by the hypothalamus via a separate pathway).⁶ There is growing evidence that the amygdala plays a crucial role in the up- or downregulation of the emotional response to pain and that this ‘nociceptive amygdala’ can be influenced by a wide range of environmental and internal stimuli to modulate the subjective experience of pain.⁷

The hippocampus, a structure with robust connections to the amygdala, is a center for memory formation, storage, and retrieval. It provides information from detailed memories that are processed by the amygdala and given a particular emotional value. The emotional value the amygdala places on a particular memory is then fed back to the hippocampus, where it integrates this information and either strengthens or weakens the memory. This is why it is believed that events associated with high emotional content (a car accident, being wounded in battle, one’s first kiss) tend to be remembered in greater detail than those with little emotional significance (the drive to work every morning). In persons with bilateral destruction of the hippocampus secondary to herpes encephalitis, there is a preservation of memory related to processes (such as tying shoes, using a fork), but a deficit in memory related to particular events, persons, and experiences along with mood problems.^8,9

In persons with post-traumatic stress disorder (PTSD), changes are seen in the amygdala, hippocampus, and other areas of the limbic system (the neural circuits of complex emotional experience). Neuroimaging studies have found consistent reductions in either total hippocampal volume or blood flow in men and women with PTSD.^10–13 The primary function of the hypothalamus is to regulate the body’s homeostatic and endocrine systems. In relation to the fear response, the hypothalamus sends projections to the medulla which controls autonomic (fight-or-flight) functions such as heart rate, muscle tone, digestion, sweating, etc.¹⁴ With input from the amygdala, the hypothalamus contributes the hormonal and autonomic component of the fear response.

The ventral tegmental area (VTA) and reticular formation (RF) are brainstem structures with projections throughout the brain. These structures are rich in dopaminergic (VTA), noradrenergic (locus coeruleus), and serotinergic (raphe nuclei) neurons. The role of neurotransmitters will be discussed in greater detail later in this chapter.

Research on other structures within this fear circuit has expanded our understanding of how the cortical structures influence the amygdala. Human brain imaging studies have found that the fusiform gyrus, prefrontal, and anterior cingulate gyrus are preferentially activated in response to fearful stimuli.^3,15 The orbitofrontal cortex (OFC), which is involved in the evaluation of risk and reward and social norms, may also have a direct role in regulation of anxiety via its connection to the amygdala (Fig. 15.2).¹⁶ The cortex, then, plays an essential role in the categorization, appraisal, and attenuation of our reactions to fearful stimuli. The higher cortical connections to the more primitive fight, flight, and reward circuitry is what allows humans to have a degree of conscious recognition and control over these processes. These connections and their conditioning form the biological basis for the effects of behavioral training used widely in the treatment of pain, such as relaxation and biofeedback.

More recent functional brain chemistry research has provided neuroanatomical evidence for the overlap between the processing and perception of pain and anxiety. In an experiment comparing patients with chronic low back pain (CLBP) to normal controls, significant differences were found in two regions of the association cortex (orbitofrontal [OFC] and dorsolateral prefrontal cortex [DLPFC]), cingulate gyrus (part of the limbic system), and thalamus.¹⁷ The study showed that persons with CLBP have differences in regional brain chemistry in the OFC and DLPFC when comparing their perception of pain. Additionally, persons with CLBP and anxiety had changes in brain chemistry suggesting increased interaction between all four brain regions, whereas anxious controls only had changes observed in the OFC. Anxiety and pain, therefore, share common neurochemical pathways and can interact in a way that leads to the reorganization of normal perceptual pathways in the brain.

DIAGNOSIS OF ANXIETY DISORDERS