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.

Symptoms of depression are transdiagnostic heterogenous features frequently assessed in psychiatric disorders, that impact the response to first-line treatment and are associated with higher suicide risk. This study assessed whether severe mental pain could characterize a specific phenotype of severely depressed high-risk psychiatric patients. We also aimed to analyze differences in treatments administered.

2,297 adult patients (1,404 females and 893 males; mean age = 43.25 years, SD = 15.15) treated in several Italian psychiatric departments. Patients were assessed for psychiatric diagnoses, mental pain, symptoms of depression, hopelessness, and suicide risk.

More than 23% of the patients reported high depression symptomatology and high mental pain (HI DEP/HI PAIN). Compared to patients with lower symptoms of depression, HI DEP/HI PAIN is more frequent among females admitted to an inpatient department and is associated with higher hopelessness and suicide risk. In addition, HI DEP/HI PAIN (compared to both patients with lower symptoms of depression and patients with higher symptoms of depression but lower mental pain) were more frequently diagnosed in patients with personality disorders and had different treatments.

Patients reporting severe symptoms of depression and high mental pain presented a mixture of particular dangerousness (high trait hopelessness and the presence of suicide ideation with more frequency and less controllability and previous suicide behaviors). The presence of severe mental pain may act synergically in expressing a clinical phenotype that is likewise treated with a more complex therapeutic regime than that administered to those experiencing symptoms of depression without mental pain.

Mental pain has been proposed as a global person-centered outcome measure. The aim of this cross-sectional study was to test an essential requisite of such a measure, namely that mental pain incorporates independent contributions from a range of discrete but disparate outcome measures.

Two hundred migraine patients were assessed concerning migraine disability, psychosomatic syndromes, mental pain, depression, anxiety, and psychosocial dimensions. General linear models were tested to verify which measures would individually make unique contributions to overall mental pain.

The final model, accounting for 44% of variance, identified that higher mental pain was associated with more severe depressive symptoms, higher migraine disability, lower well-being, and poorer quality of life.

In this sample, mental pain was shown to behave as expected of a global outcome measure, since multiple measures of symptomatology and quality of life showed modest but significant bivariate correlations with mental pain and some of these measures individually made unique contributions to overall mental pain.

Pain has been qualified under four categories: nociception, perception of pain, suffering, and pain behaviors. Most of the literature on migraine has devoted attention to the first two. The aim of the present cohort study was to investigate patients with migraine enrolled at a tertiary care unit to study suffering and mental pain and identify potential risk factors for migraine.

An observational cross-sectional study was carried out on patients with chronic migraine (CM) and episodic migraine (EM), and healthy subjects (HS). The three groups were matched for age and sex. A comprehensive assessment of migraine disability, pain, psychiatric disorders, psychosomatic syndromes, depressive and anxious symptoms, euthymia, psychosocial variables, mental pain, and pain-proneness (PP) was performed.

Three hundred subjects were enrolled (100 CM, 100 EM, and 100 HS). Based on the multiple regression analyses, those presenting PP (social impairment: odds ratio [OR] = 3.59, 95% confidence interval [CI] = 1.14-11.29; depressive symptoms: OR = 3.82, 95% CI = 1.74-8.41) were more likely to be CM than HS. Those with higher levels of PP (social impairment: OR = 4.04, 95% CI = 1.60-10.22; depressive symptoms: OR = 2.02, 95% CI = 1.26-3.24) were more likely to be EM than HS. Those presenting higher levels of mental pain were more likely to be CM than EM (OR = 1.45, 95% CI = 1.02-2.07).

Migraine is an unpleasant sensory and emotional experience associated with psychosocial manifestations that might contribute to the level of suffering of the individuals. Mental pain resulted to be the variable that most differentiated patients with CM from EM.

In the Israel Defense Forces (IDF) as well as in most armies throughout the world, the leading cause of death during peace-time is suicide. This study examines emotional regulation of mental pain as a contributor to suicidal ideation in soldiers.

One hundred sixty-eight IDF soldiers (aged 18–21 years, 59% males) completed the following self-report questionnaires: Scale for Suicide Ideation (SSI); Orbach & Mikulincer Mental Pain Scale (OMMP); and Emotional Regulation of Mental Pain questionnaire. Participants were divided into 3 groups: soldiers who attempted suicide (AS group, n = 58), soldiers under treatment by a mental health professional and reporting no suicidal behavior (PT group, n = 58), and controls (C group, n = 50).

Suicide ideation, mental pain, and low emotional regulation were significantly higher in the suicidal group as compared to the two other groups (P < 0.001). Mental pain was significantly related to more suicide ideation in soldiers with low ability to regulate mental pain (P < .001 for the interaction).

Emotional regulation of mental pain moderates the link between mental pain and suicide ideation. Soldiers with high mental pain and low regulation of mental pain exhibited higher suicidal ideation. These findings may assist in planning prevention programs in the army and similar settings.