Threat Response System: Parallel Brain Processes in Pain vis-à-vis Fear and Anxiety

Igor Elman, David Borsook

Pain is essential for avoidance of tissue damage and for promotion of healing. Notwithstanding the survival value, pain brings about emotional suffering reflected in fear and anxiety, which in turn augment pain thus giving rise to a self-sustaining feedforward loop. Given such reciprocal relationships, the present article uses neuroscientific conceptualizations of fear and anxiety as a theoretical framework for hitherto insufficiently understood pathophysiological mechanisms underlying chronic pain. To that end, searches of PubMed-indexed journals were performed using the following Medical Subject Headings' terms: pain and nociception plus amygdala, anxiety, cognitive, fear, sensory, and unconscious. Recursive sets of scientific and clinical evidence extracted from this literature review were summarized within the following key areas: (1) parallelism between acute pain and fear and between chronic pain and anxiety; (2) all are related to the evasion of sensory-perceived threats and are subserved by subcortical circuits mediating automatic threat-induced physiologic responses and defensive actions in conjunction with higher order corticolimbic networks (e.g., thalamocortical, thalamo-striato-cortical and amygdalo-cortical) generating conscious representations and valuation-based adaptive behaviors; (3) some instances of chronic pain and anxiety conditions are driven by the failure to diminish or block respective nociceptive information or unconscious treats from reaching conscious awareness; and (4) the neural correlates of pain-related conscious states and cognitions may become autonomous (i.e., dissociated) from the subcortical activity/function leading to the eventual chronicity. Identifying relative contributions of the diverse neuroanatomical sources, thus, offers prospects for the development of novel preventive, diagnostic, and therapeutic strategies in chronic pain patients.