Expectation of pain and relief: a dynamical model of the neural basis for pain-trauma co-morbidity

Author: Irina A Strigo1, A D Bud Craig2, Alan N Simmons3
Affiliation: <sup>1</sup> Emotion and Pain Laboratory, San Francisco Veterans Affairs Health Care Center, 4150 Clement Street, San Francisco, CA 94121, USA; Department of Psychiatry, University of California San Francisco, 401 Parnassus Ave, San Francisco, CA 94143, USA. <sup>2</sup> Emotion and Pain Laboratory, San Francisco Veterans Affairs Health Care Center, 4150 Clement Street, San Francisco, CA 94121, USA; Department of Psychiatry, University of California San Francisco, 401 Parnassus Ave, San Francisco, CA 94143, USA; Center of Excellence in Stress and Mental Health, San Diego Veterans Affairs Health Care Center, 3350 La Jolla Village Dr, San Diego, CA 92161, USA; Stress and Neuroimaging Laboratory, San Diego Veterans Affairs Health Care Center, 3350 La Jolla Village Drive, MC 151-B, San Diego, CA 92161, USA; Department of Psychiatry, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA. <sup>3</sup> Center of Excellence in Stress and Mental Health, San Diego Veterans Affairs Health Care Center, 3350 La Jolla Village Dr, San Diego, CA 92161, USA; Stress and Neuroimaging Laboratory, San Diego Veterans Affairs Health Care Center, 3350 La Jolla Village Drive, MC 151-B, San Diego, CA 92161, USA; Department of Psychiatry, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Conference/Journal: Neurosci Biobehav Rev
Date published: 2024 Jun 5
Other: Pages: 105750 , Special Notes: doi: 10.1016/j.neubiorev.2024.105750. , Word Count: 214


Posttraumatic Stress Disorder (PTSD) is highly co-morbid with chronic pain conditions. When present, PTSD significantly worsens chronic pain outcomes. Likewise, pain contributes to a more severe PTSD as evidenced by greater disability, more frequent use of harmful opioid analgesics and increased pain severity. The biomechanism behind this comorbidity is incompletely understood, however recent work strongly supports the widely-accepted role of expectation, in the entanglement of chronic pain and trauma symptoms. This work has shown that those with trauma have a maladaptive brain response while expecting stress and pain, whereas those with chronic pain may have a notable impairment in brain response while expecting pain relief. This dynamical expectation model of the interaction between neural systems underlying expectation of pain onset (traumatic stress) and pain offset (chronic pain) is biologically viable and may provide a biomechanistic insight into pain-trauma comorbidity. These predictive mechanisms work through interoceptive pathways in the brain critically the insula cortex. Here we highlight how the neural expectation-related mechanisms augment the existing models of pain and trauma to better understand the dynamics of pain and trauma comorbidity. These ideas will point to targeted complementary clinical approaches, based on mechanistically separable neural biophenotypes for the entanglement of chronic pain and trauma symptoms.

Keywords: anticipation; anxiety; imaging; insula; pain; striatum.

PMID: 38849067 DOI: 10.1016/j.neubiorev.2024.105750