When Stress Hurts: Central Nervous System

In establishing the connection between the onset of psychogenic pain and stress, it is important to notice that pain and stress share the same central nervous system (CNS) pathways and structures. In this second post in the series on the close association between psychological stress and psychogenic pain, we’ll take a look at these shared structures.

CNS Structures Mobilized by Pain and Stress

PendulumThe body’s response to pain engages a large number of CNS structures that are often the same as the ones activated by the stress reaction. The afferent pathways that carry pain signals connect to the thalamic nuclei and from there to the somatosensory, insular and anterior cingulate (ACC) portions of the brain cortex. A recent functional MRI (fMRI) study (Keltner et al., 2006) on the effects of pain expectation on pain transmission provides the best evidence for the activation of the rostral ACC (rACC), periaqueductal gray (PAG), and medial prefrontal cortex. This and other imaging studies provide evidence of a bidirectional pain pathway receiving input from the limbic system and the amygdala, converging on the PAG, traveling through the pontomedullar nuclei, and controlling spinal pain transmission neurons (Fields, 2000; Fields & Martin, 2001). As the authors of this study point out, “expectation for a higher intensity noxious stimulus increases subjectively experienced pain intensity in part through the action of a descending pathway that facilitates nociceptive transmission at and/or caudal to the region of the contralateral nucleus cuneiformis (nCF)” (p. 4442). The nCF, in humans and other primates, has a composition similar to the PAG and its neurons project directly into the rostroventral medulla, the hypothalamus and the amygdala, all structures directly involved in modulation of the stress reaction.

PMR_muscle-crampsLikewise, the body’s stress response engages a large number of the same CNS structures, specifically certain subregions of the hypothalamus such as the paraventricular nucleus (PVN), the amygdala, and the periaqueductal grey; and certain cortical brain structures, such as the medial prefrontal cortex and subregions of the anterior cingulate and insular cortices (Maier, 2003). These structures provide output to the pituitary and pontomedullar nuclei, which in their turn stimulate the body’s neuroendocrine secretions, as well as to the hypothalamic-pituitary-adrenal (HPA) axis, the endogenous pain modulation system, and the ascending aminergic pathways. The feedback controlling the stress response is provided by the serotonergic (raphe) and noradrenergic (locus ceruleus) structures and by the levels of glucocorticoids in the blood stream, which provide inhibitory impulses to the medial prefrontal cortex and to the hippocampus. Corticotrophin releasing hormone (CRH) is the fundamental chemical substances mediating the stress response, which is secreted by PVN, amygdala, and locus ceruleus neurons. Acute or chronic stress can temporarily or permanently modify the level of responsiveness and output of the CNS to stress (Bennett et al., 1998).

Sharing Pathways, Sharing Outcomes

With this significant convergence of pathways, neurochemical activity and CNS structure activation, it should come as no surprise that acute stress can provoke physical pain, often in the head, the muscles, and the abdominal region. Equally unsurprising is that pain, especially when sharp and unexpected, is in itself a cause of stress that mobilizes the body into immediate action (think of the hand that immediately goes to cover the cut or the burn). Continuous pain, of any origin, is inherently stressful. Continuous stress can be, and often is, manifested by otherwise unexplained (thus psychogenic) physical pain.

Previously in this series: When Stress Hurts: Psychogenic Pain


  • The Neurochemistry of Psychogenic Pain and Stress
  • Psychological Stressors and the Sudden Appearance of Psychogenic Pain
  • Fibromyalgia, Severe Headaches and Other Stress-Related Misery
  • Medical and Non-Medical Treatments for Stress and Psychogenic Pain