Researchers explore the biology of painful experiences not primarily felt in the body (‘non-physical pain’), sometimes referred to as mental, social or emotional pain. A critical challenge lies in how to operationalise this subjective experience for biological research, a crucial process for translating findings into clinical practice.

To map studies investigating biological features of non-physical pain, focusing on their conceptual features (i.e. terms and definitions of non-physical pain) and methodological characteristics (e.g. experimental paradigms and measures).

This methodological systematic review searched reports of primary research on the biological features of non-physical pain across Embase, MEDLINE and Web of Science. Using a meta-research approach, we synthetised results on terms, definitions, populations, experimental paradigms, confounders, measures of non-physical pain and investigation methods (e.g. functional magnetic resonance imaging).

We identified 92 human studies, involving 7778 participants. Overall, 59.1% of the studies did not report any definition of non-physical pain, and 82% of studies did not use a specific measure. Regarding the possibility of translating results to clinical settings, most of the human studies involved only healthy participants (71.7%) and the seven different experimental paradigms used to induce non-physical pain had unknown external validity. Confounders were not considered by 32.4% of the experimental studies. Animal studies were rare, with only four rodent studies.

Biomedical studies of non-physical pain use heterogeneous concepts with unclear overlaps and methods with unknown external validity. As has been done for physical pain, priority actions include establishing an agreed definition and measurement of non-physical pain and developing experimental paradigms with good external validity.

Disturbances in social interaction are a defining feature of patients with borderline personality disorder (BPD). In this study, facial emotional expressions, which are crucial for adaptive interactions in social contexts, were assessed in patients with BPD in response to social exclusion.

We examined facial emotional reactions of 35 patients with BPD and 33 healthy controls when playing Cyberball, a virtual ball-tossing game that reliably induces social exclusion. Besides self-reported emotional responses, facial emotional expressions were analyzed by applying the Emotional Facial Action Coding System (EMFACS).

Patients with BPD showed a biased perception of participation. They more readily reported feeling excluded compared to controls even when they were included. In BPD, social exclusion led to an increase in self-reported other-focused negative emotions. Overall, EMFACS analyses revealed that BPD patients reacted with fewer positive expressions and with significantly more mixed emotional expressions (two emotional facial expressions at the same time) compared to the healthy control group when excluded.

Besides a negative bias for perceived social participation, ambiguous facial emotional expressions may play an important role in the disturbed relatedness in patients with BPD.