Altered Pain Perception and Fear-Learning Deficits in Subjects With Posttraumatic Stress Disorder

Abstract

There is growing evidence that fear learning abnormalities are involved in the development of posttraumatic stress disorder (PTSD) and chronic pain. More than 50% of PTSD patients suffer from chronic pain. This study aimed to examine the role of fear-learning deficits in the link between pain perception and PTSD. We included 19 subjects with PTSD and 21 age- and sex-matched healthy control subjects in a fear-conditioning experiment. The conditioned stimulus (CS) consisted of visual signs flashed upon a screen in front of each subject. The unconditioned stimulus was either a low or high temperature impulse delivered through a thermal contact thermode on the subjects’ hand. A designation of ‘CS−’ was assigned to CS always followed by nonpainful low-temperature stimuli; a designation of ‘CS+’ was given to CS that were randomly followed by either a low or a more painful high temperature. Skin conductance was used as a physiological marker of fear. In healthy control subjects, CS+ induced more fear than CS−, and a low-temperature stimulus induced less subjective pain after CS− than after CS+. PTSD subjects failed to demonstrate such adaptive conditioning. Fear ratings after CS presentation were significantly higher in the PTSD group than in the control group. There were significant interaction effects between group and the type of CS on fear and pain ratings. Fear-learning deficits are a potentially promising, specific psychopathological factor in altered pain perception associated with PTSD. Deficits in safety learning may increase fear and, consequently, pain sensations. These findings may contribute to elucidating the pathogenesis behind the highly prevalent comorbidity that exists between PTSD and pain disorders, and to developing new treatments.

Inactivation of the Ventrolateral Orbitofrontal Cortex Impairs Flexible Use of Safety Signals

“…Heightened fear is a hallmark symptom of PTSD (Yehuda et al, 2015) and failure to utilize learned safety cues has been suggested as a biomarker of PTSD (Grillon and Morgan, 1999; Jenewein et al, 2016; Jovanovic et al, 2009; Jovanovic et al, 2012). What is striking about this phenomenon is that while individuals with PTSD understand the meaning of the safety cue, fear enhanced startle and other biomarkers of anxiety appear insensitive to regulation by the safety cue (Jovanovic et al, 2009).…”

Sex differences in fear discrimination do not manifest as differences in conditioned inhibition

“…Further, when a safety cue is well learned, it can reduce fear in the presence of a danger cue, a learning phenomenon known as conditioned inhibition of fear (Kazama et al 2013). Overgeneralization of fearrelated cues and aberrant conditioned inhibition of fear are seen in individuals with post-traumatic stress disorder (PTSD) (Jovanovic et al 2012;Costanzo et al 2016;Jenewein et al 2016). Females are more likely to be diagnosed with PTSD than males (Kilpatrick et al 2013;Kessler et al 1995) and safety learning and discrimination are sensitive to hormonal birth control and trauma history in females compared with males (Gamwell et al 2015;Lornsdorf et al 2015).…”

Prevalence and correlates of somatization in anxious individuals in a Chinese online crisis intervention during COVID-19 epidemic

“…Stress is believed to be a physiological trigger for the descending pain regulation system, and pain can trigger an emotional response to stress ( Timmers et al 2019 ). Pain sensitivity may increase under chronic stress ( Jenewein et al, 2016 ). Both chronic stress and chronic pain are associated with certain brain networks, including the corticolimbic system and thalamus, and are both associated with increased anxiety (Vachon-Presseau et al 2018; Timmers et al 2019 ).…”