Sex Differences Linking Pain-Related Fear and Interoceptive Hypervigilance: Attentional Biases to Conditioned Threat and Safety Signals in a Visceral Pain Model

Abstract

Although the broad role of fear and hypervigilance in conditions of the gut-brain axis like irritable bowel syndrome is supported by converging evidence, the underlying mechanisms remain incompletely understood. Even in healthy individuals, it remains unclear how pain-related fear may contribute to pain-related attentional biases for acute visceral pain. Building on our classical fear conditioning work in a clinically relevant model of visceral pain, we herein elucidated pain-related attentional biases shaped by associative learning in healthy women and men, aiming to elucidate possible sex differences and the role of psychological traits. To this end, we compared the impact of differentially conditioned pain-predictive cues on attentional biases in healthy women and men. Sixty-four volunteers accomplished a visual dot-probe task and subsequently underwent pain-related fear conditioning where one visual cue (CS + ) was contingently paired with a painful rectal distention (US) while another cue remained unpaired (CS − ). During the following test phase, the dot-probe task was repeated to investigate changes in attentional biases in response to differentially valenced cues. While pain-related learning was comparable between groups, men revealed more pronounced attentional engagement with the CS + and CS − whereas women demonstrated stronger difficulties to disengage from the CS + when presented with a neutral cue. However, when both CS + and CS − were presented together, women revealed stronger difficulties to disengage from the CS − . Regression analyses revealed an interaction of sex, with negative affect predicting stronger avoidance of the CS + and stronger difficulties to disengage attention from the CS − in men. These results provide first evidence that pain-related fear conditioning may induce attentional biases differentially in healthy women and men. Hence, sex differences may play a role in attentional mechanisms underlying hypervigilance, and may be modulated by psychological vulnerability factors relevant to chronic visceral pain.

A psychometric evaluation of the Italian short version of the Fear of Pain Questionnaire-III: Psychometric properties, measurement invariance across gender, convergent, and discriminant validity

“… Courbalay et al (2016) hypothesize a significant mediating role of neuroticism on the level of female fear of severe and medical pain. The increased sensitivity to medical pain in females is also reported by more recent studies such as Heft et al (2007) , Katanec et al (2018) , McLenon and Rogers (2019) , and Labrenz et al (2020) . In addition, female seem to have a significantly higher perceived pain intensity than men, which could also explain these findings ( Diotaiuti et al, 2022b ).…”

Fear Extinction-Based Inter-Individual and Sex Differences in Pain-Related Vocalizations and Anxiety-like Behaviors but Not Nocifensive Reflexes

“…However, sex differences in pain-related amygdala neuroplasticity are largely unknown, though one clinical study reported sex differences in resting-state amygdala subnuclei connectivity patterns as a potential explanation for the increased prevalence of conditions of negative affect in women [95]. Even less has been explored about inter-individual and sex differences in fear learning and FE with regard to pain and pain modulation, though a clinical study reported sex differences in pain-related fear conditioning [96]. Ultrasonic vocalizations were previously associated increased neuronal activity in brain regions regulating fear and anxiety, including the amygdala [97], and have been demonstrated to be an effective indicator of emotional status in pain models [20,21,27].…”

Sesgos atencionales y estrategias de distracción: implicaciones para la comprensión y tratamiento del dolor

“…Desde una perspectiva cognitiva, se han estudiado la atención y la hipervigilancia como dos factores importantes para determinar su relación con el dolor (Dimova et al, 2013;Labrenz et al, 2020;Van Damme et al, 2010;Vervoort et al, 2011Vervoort et al, , 2013. Se ha sugerido que la experiencia dolorosa implica una demanda considerable de recursos atencionales (Vervoort et al, 2013).…”