Towards a better definition of nociplastic pain conditions: a psychological grounded study on fibromyalgia, chronic headache and vulvodynia.

Chronic pain (CP) is defined as pain that has lasted for more than three months. Its prevalence ranges from 11% to 40% (Dahlhamer, 2018 ), and CP has been observed to have an impact on quality of life, relationships, self-esteem, and psychopathology (Dueñas et al., 2016 ; Fitzcharles et al., 2021 ; Katz et al., 2015 ). The International Association for the Study of Pain (IASP; Raja et al., 2020 ) has proposed the differentiation of three subtypes of CP based on their causal mechanisms: nociceptive (i.e. associated with an actual or threatened tissue injury), neuropathic (i.e. caused by an injury or disease affecting the peripheral or central nervous system), and nociplastic. Nociplastic Pain (NP) (Raja et al., 2020 ) encompasses all conditions resulting from altered nociception without clear evidence of actual or threatened tissue damage. In this sense, NP encompasses several clinical conditions with common neurophysiologic mechanisms, such as fibromyalgia (FM), chronic headache (CH), and vulvodynia (VU) (Bergeron et al., 2020 ; Fitzcharles et al., 2021 ), often accompanied by other central nervous system (CNS)-related symptoms such as fatigue and cognitive problems, hypersensitivity to environmental stimuli, and psychological symptoms including anxiety and depression (Fitzcharles et al., 2021 ). Specifically, FM is a chronic syndrome characterized by widespread musculoskeletal pain associated with fatigue, nonrestorative sleep, and cognitive deficits (Wolfe et al., 2016 ). Its prevalence ranges from 0.2% to 6.6%, with a significant increase among women, ranging from 2.4% to 6.8% (Marques et al., 2017 ). CH affects about 15% of the world's population, and it is typically characterized by recurrent and disabling attacks of severe headache, nausea, vomiting, hypersensitivity to light and sound, and other physical, mental, and psychological variables and symptoms, lasting from 4 to 72 h (Ferrari et al., 2022 ). VU is a condition characterized by persistent vulvar pain, described as sharp and burning, occurring in the absence of relevant visible factors or a specific, clinically identifiable neurological disorder (Bornstein et al., 2016 ). Population-based estimates indicate that the lifetime prevalence of VU ranges from 8 to 10% (Harlow et al., 2014 ). The association between CH, FM, and VU, as well as their link with psychological factors such as early traumatic events, anxiety, depression, alexithymia, and dissociation, is well-established (Bergeron et al., 2020 ; Fitzcharles et al., 2021 ). However, these CP disorders have typically been studied as distinct conditions. One possible mechanism underlying all these syndromes is central sensitization (CS). CS is defined as an ‘increased responsiveness of CNS nociceptive neurons to normal or subthreshold afferent inputs’ (Wolfe et al., 2011 ). It encompasses multiple CNS dysfunctions, contributing to both the transition from acute to chronic pain and the amplification of pain in existing chronic pain conditions (Arendt-Nielsen et al., 2018 ). CS provides a common mechanism that explains the complex conditions typical of CP and the symptomatology it presents. This symptomatology is often expressed in multiple comorbid syndromes (Nijs et al., 2021 ). To study the role of central sensitization (CS), it is necessary to examine perpetuating psychological factors, such as catastrophizing, perception of illness, fear, anxiety, depression, maladaptive defense mechanisms, childhood experiences (especially if traumatic), and emotional processes, such as emotional awareness and emotional regulation (Nijs et al., 2023 ). Therefore, in the present study, we are going to examine some of these psychological factors, particularly traumatic experiences, defense mechanisms, and alexithymia, in women with NP syndromes. So far, FM, CH, and VU have been studying in isolation. The intent of this paper is to compare these disorders by also considering mixed forms, that is, women with these syndromes in comorbidity. Psychological trauma is defined as a subjective experience in which an individual is exposed to events or situations that exceed their ability to cope with them, causing a response of intense fear and/or helplessness (Bromberg, 2014 ). Such events may include physical and emotional abuse, neglect, accidents, and natural disasters. These, especially if experienced during childhood, can increase vulnerability to developing CP conditions (Manuel et al., 2023 ). The impact of trauma on the individual can be profound, manifesting in alterations to pain perception and stress response, which can, in turn, predispose the individual to persistent somatic manifestations. Several studies have, in fact, reported positive associations between traumatic experiences and the development of CP conditions (Borsini et al., 2014 ; Chandan et al., 2020 ; Fishbain et al., 2017 ; Nicol et al., 2016 ; Otis et al., 2003 ). In the event of encountering trauma, an individual may engage defense mechanisms as a spontaneous psychological response to shield the ego from distressing emotions and contemplations. Defense mechanisms are automatic psychological processes that operate outside of awareness and protect the individual from painful or unacceptable emotions or thoughts (Vaillant, 1994 ). A distinction has been made between mature and immature defense mechanisms; the latter may contribute to the manifestation or exacerbation of chronic pain, as the individual may not be aware of the underlying emotions that influence pain perception (Di Giuseppe & Perry, 2021 ; van Middendorp et al., 2016 ). These mechanisms encompass a range of strategies, including dissociation, where an individual may disengage their thoughts and emotions to alleviate distress, and alexithymia, which can emerge as a defensive response to trauma, thereby limiting emotional awareness (Lanius et al., 2010 ). Alexithymia describes an individual's difficulty in recognizing, identifying, and describing their emotions and those of others. This deficit can interfere with emotional self-regulation, leading to limited emotional communication and reduced empathic ability (Sifneos, 1973 ). In addition, individuals with alexithymia have difficulty distinguishing emotional signals from physical ones, thus leading to the somatization of emotions, which manifests as persistent physical pain. It has been observed that alexithymia has an association with pain severity and impairment (Galli et al., 2017 ; Habibi Asgarabad et al., 2023 ; Lumley et al., 2002 ). The general aim of the present study is to better understand the psychological functioning of women presenting different conditions under CP (CH, FM, VU, and MIX) to identify and discuss similarities and differences. Specifically, we aim to: explore possible significant differences in the domain of traumatic experiences among the evaluated groups, with a particular focus on experiences related to emotional neglect, emotional abuse, body threat, sexual approach, and sexual abuse; explore any significant differences among the evaluated groups in overall defensive functioning, distinguishing levels of defense into mature, neurotic, and immature; explore any significant differences in the domain of alexithymia, such as difficulty in identifying and describing feelings and an outward-oriented thinking style, among the assessed groups. explore possible significant differences in the domain of traumatic experiences among the evaluated groups, with a particular focus on experiences related to emotional neglect, emotional abuse, body threat, sexual approach, and sexual abuse; explore any significant differences among the evaluated groups in overall defensive functioning, distinguishing levels of defense into mature, neurotic, and immature; explore any significant differences in the domain of alexithymia, such as difficulty in identifying and describing feelings and an outward-oriented thinking style, among the assessed groups. We hypothesized that each pure group would show a similar pattern of impairment for each variable, with unique characteristics, and that the mixed group would differ significantly from the single conditions. Furthermore, a comparison was made between the CP groups and a control group of healthy women to comprehend the impact and effect of CP on psychological variables, including those examined in this study, and the effect of pain. The hypothesis is that individuals with CP encounter not only a physical experience but also a psychological experience; these psychological differences may be associated with how individuals react to stress, how they process emotions, and how they cope with pain. By comparing these groups, it is possible to distinguish between the effects of chronic pain and preexisting psychological variables.

The study data were collected as part of a larger research project aimed at evaluating the impact of psychological factors on the course of CP in patients. These factors included traumatic events, psychological distress, personality traits, psychological pain, sensitivity to environmental stimuli, and impact on the sexual sphere. A total of 1237 Italian women participated in this study. They were recruited through a snowball technique involving CH, FM, and VU patient associations, who shared the web survey through their institutional websites and social media platforms such as Facebook, Instagram, and LinkedIn. The survey was administered online via Google Forms, and data collection occurred between April 2023 and January 2024. Participants were required to provide informed consent before taking part in the survey. They were asked to disclose details about their CP diagnosis, including the year it was determined and the healthcare professional or medical facility responsible for the diagnosis. The survey ensured anonymity, and participants did not receive any compensation for their involvement. To be eligible, participants had to identify as cisgender women, be at least 18 years old, be proficient in Italian, and have received a diagnosis of CH, FM, and/or VU from a specialist physician (neurologist or rheumatologist) for at least six months. Regarding the sample of HC women, they, too, were recruited via snowball sampling on social media platforms, including Facebook, Instagram, and LinkedIn. Once again, the survey was administered online through Google Forms, and data collection occurred between April 2023 and January 2024. The survey ensured anonymity, and participants did not receive any compensation for their involvement. To be eligible, participants had to identify as cisgender women, be at least 18 years old, be proficient in Italian, and not have received a diagnosis of CP. Dal total of 1237, after excluding 93 responses (7.52%) that did not meet the inclusion criteria or were duplicate records, the final group consisted of 1144 participants who completed the mandatory survey. The test that addressed alexithymia was part of the protocol's optional (voluntary) portion, which was completed by 1006 out of 1144 participants. A detailed description of the self-report protocol is provided in the Measures section. Table 1 summarizes the sociodemographic characteristics of the 1006 women who completed the voluntary part and were included in this study. In fact, all analyses were done on the sample consisting of these 1006 women. Table 1. Sociodemographic data and description of the participants ( n  = 1006).   Total Group ( n  = 1006) Chronic Headache (CH) ( n  = 195) Fibromyalgia (FM) ( n  = 186) Vulvodynia (VU) ( n  = 193) Mixed Condition (Mix) ( n  = 315) Healthy Controls (HC) ( n  = 117) Significance   M  ± SD M  ± SD M  ± SD M  ± SD M  ± SD M  ± SD F (4, 1001) Age 40.71 ± 13.31 39.92 ± 12.39 46.58 ± 12.15 32.36 ± 10.99 44.40 ± 12.52 36.50 ± 13.8 43.519 df   =   4 p  < .001   n (%) n (%) n (%) n (%) n (%) n (%) Chi-squared Sexual Orientation             26.908 df = 12 p  = .008  Heterosexual 923 (91.75) 174 (89.23) 179 (96.24) 171 (88.60) 295 (93.65) 104 (88.89)  Bisexual, Pansexual or Polisexual 59 (5.86) 13 (6.67) 3 (1.61) 13 (6.74) 18 (5.71) 12 (10.26)  Lesbian 14 (1.39) 4 (2.05) 4 (2.15) 5 (2.59) 0 1 (0.85)  Asexual spectrum 10 (0.99) 4 (2.05) 0 4 (2.07) 2 (0.63) 0 Civil status             102.258 df = 16 p  < .001  Single 382 (37.97) 77 (39.49) 44 (23.66) 104 (53.89) 95 (30.16) 62 (52.99)  Married/Civil Union 378 (37.57) 78 (40.00) 96 (51.61) 34 (17.62) 142 (45.08) 28 (23.93)  Separated/Divorced 81 (8.05) 12 (6.15) 18 (9.68) 7 (3.63) 36 (11.43) 8 (6.84)  Widowed 8 (0.80) 0 2 (1.08) 1 (0.52) 4 (1.27) 1 (0.85)  Cohabitant 157 (15.61) 28 (14.36) 26 (13.98) 47 (24.35) 38 (12.06) 18 (15.38) Current relational status             – p   =  .134  Single 210 (20.87) 32 (16.41) 40 (21.51) 34 (17.62) 73 (23.17) 31 (26.50)  Monogamous couple 782 (77.73) 157 (80.51) 143 (76.88) 158 (81.87) 239 (75.87) 85 (72.65)  Polyamorous/non-monogamous 14 (1.39) 6 (3.08) 3 (1.61) 1 (0.52) 3 (0.95) 1 (0.85) Education degree             72.374 df = 16 p   <  .001  Primary school 1 (0.10) 0 0 1 (0.52) 0 0  Middle school 72 (7.16) 8 (4.10) 23 (12.37) 3 (1.55) 32 (10.16) 6 (5.13)  High school 420 (14.75) 78 (40.00) 90 (48.39) 69 (35.75) 153 (48.57) 30 (25.64)  Degree 387 (38.47) 83 (42.56) 61 (32.80) 92 (47.67) 97 (30.79) 54 (46.15)  Post-degree 126 (12.52) 26 (13.33) 12 (6.45) 28 (14.51) 33 (10.48) 27 (23.08) Work Status             88.604 df = 12 p  = <.001  Unemployed 193 (19.18) 47 (24.10) 40 (21.51) 20 (10.36) 76 (24.13) 10 (8.55)  Student 136 (13.52) 25 (12.82) 7 (3.76) 50 (25.91) 4 (7.62) 30 (25.64)  Employed 629 (62.52) 117 (60.00) 124 (66.67) 120 (62.18) 197 (6.54) 71 (60.68)  Retired 48 (4.77) 6 (3.08) 15 (8.06) 3 (1.55) 18 (5.71) 6 (5.13) Socio-economic status             – p  = .070  Low 112 (11.13) 18 (9.23) 26 (13.98) 17 (8.81) 43 (13.65) 8 (6.84)  Middle-Low 269 (26.74) 45 (23.08) 55 (29.57) 47 (24.35) 95 (30.16) 27 (23.08)  Middle 542 (53.88) 108 (55.38) 93 (50.00) 112 (58.03) 160 (50.79) 69 (58.97)  Middle-High 78 (7.75) 22 (11.28) 12 (6.45) 15 (7.77) 16 (5.08) 13 (11.11)  High 5 (0.50) 2 (1.03) 0 2 (1.04) 1 (0.32) 0 Note: N  = 991 (98.51) are Caucasian white. Sociodemographic data and description of the participants ( n  = 1006). Note: N  = 991 (98.51) are Caucasian white. The participants in the study had a mean age of 40.71 years (range: 18–75 years). Most of them identified as heterosexual and reported to be in a monogamous relationship. The majority had moderate to moderately high levels of education, corresponding to a high school diploma or university degree. Nearly 63% of participants were employed at the time of the survey. Most participants (98.51%) identified as white Caucasian and lived in small towns or cities with a medium to medium-low socioeconomic status. All participants received a diagnosis of CP between 1982 and 2022, primarily from specialized physicians such as neurologists, rheumatologists, and gynecologists. The study categorized participants into five groups based on self-reported diagnosis: chronic headache (CH), fibromyalgia (FM), vulvodynia (VU), mixed condition (MIX), and healthy controls (HC, women who reported no history of chronic pain related to the three diagnoses considered for the study). The MIX group included participants with two or more diagnoses between CH, FM, and VU. Out of the total sample size of 315, 55 individuals (17.46%) were diagnosed with CH, FM, and VU, 183 individuals (58.09%) were diagnosed with FM and CH, 44 individuals (13.97%) were diagnosed with FM and VU, and 33 individuals (10.48%) were diagnosed with CH and VU. The research project utilized a protocol consisting of several self-report measures to investigate specific psychological variables. To avoid burdening participants, the protocol was divided into a mandatory part, which 1144 participants completed, and a voluntary part, which 1006 women completed. The assessment took approximately 30 min to complete for the mandatory part and an additional 10 min for the voluntary section. This study focuses on the data collected from the 1006 participants who completed the voluntary section. The questionnaires used in this study are: Sociodemographic questionnaire : participants completed a sociodemographic form to provide general information, including age, gender, sexual orientation, marital and relational status, education level, work status, socioeconomic status, ethnicity, area of residence, and relevant information about the diagnosis of FM, CH, VU, and other CP conditions. Traumatic Experiences Checklist (TEC; Nijenhuis et al., 2002 ): an instrument that investigates 29 types of potential trauma. These include the events listed in criterion A of Post Traumatic Stress Disorder (PTSD), as well as other potentially overwhelming events such as loss of significant others, life-threatening illness or aggression, the experience of war, emotional neglect, emotional abuse, physical abuse, sexual harassment, and sexual trauma. TEC can be calculated with different scores. In this study, we used only item A of the 29 presents to investigate the presence or absence of a traumatic experience. The questionnaire comprises a total score for complex trauma and five subscales that investigate emotional neglect, emotional abuse, bodily threat, sexual approach, and sexual abuse. Higher scores indicate a more significant presence and relevance of traumatic experiences. According to previous studies conducted on Italian samples (Craparo et al., 2013 ; Schimmenti, 2018 ), the measure's reliability was found to be satisfactory. Specifically, the Cronbach's alpha coefficient consistently exceeded 0.7, with notable values of 0.65 and 0.72 observed in the cited studies. In the present study, Cronbach’s alpha coefficient was 0.762. Defense Mechanism Rating Scales – Self-Report (DMRS-SR-30; Di Giuseppe et al., 2020 ): it consists of 30 items scored on a 5-point Likert scale (ranging from not at all to very often/very often). It identifies 30 individual defense mechanisms organized hierarchically into various levels based on functional similarity and adaptability. The defense levels are further categorized as mature, neurotic, and immature. Elevated scores indicate a greater utilization of the respective defense mechanism. The instrument has good reliability (Di Giuseppe et al., 2020 ) with a Cronbach's alpha = 0.890; similarly, in the present study, Cronbach's alpha was found to be = 0.895. Toronto Alexithymia Scale-20 (TAS-20; Bagby et al., 1994 ): the most used instrument for assessing alexithymia. It is a 20-item questionnaire scored on a 5-point Likert scale (ranging from strongly disagree to strongly agree). Total scores range from 20 to 100, with a score of 61 or higher indicating alexithymia. The TAS-20 consists of three factors: difficulty identifying feelings, difficulty describing feelings to others, and an externally oriented thinking style. In the present work, the Cronbach's coefficient was 0.776; in the Italian validation (Bressi et al., 1996 ), the instrument showed good reliability with a Cronbach's coefficient of 0.82. First, sociodemographic descriptive data were discussed, highlighting the characteristics of women reporting CP divided into five groups (CH, FM, VU, MIX, and HC). Age was defined as a covariate for each analysis of variance (ANOVA) and regression model included in the study due to the differences between the groups and their potential impact on psychological variables and CP manifestation. To analyse differences in psychological variables among groups of women reporting CP, ANCOVA, and MANCOVA (multivariate analysis of covariance) were performed. Bonferroni Post Hoc analyses were performed to specify differences between groups. All data were analysed using Jamovi version 2.4.11. To ensure sufficient statistical power (0.80), a predetermined minimum of 269 participants was calculated a priori for the ANCOVA with GPower 3.1. These analyses involved five groups and one covariate, requiring a minimum effect size of 0.25. The effective sample size for the ANCOVA analyses ultimately reached 1006 participants (resulting in a post-hoc observed statistical power of 1).

Descriptive statistics of the socio-demographic variables assessed in this study between the groups are presented in Table 1 . Groups differed significantly in age ( F  = 43.519; df = 4; p  < .01). Bonferroni post hoc tests showed that the FM and MIXs were significantly older than CH and HC. Furthermore, the groups exhibit significant differences in sexual orientation, marital status, education, and employment status. It is possible that age differences played a significant role in these variations, as older participants tend to be married, have higher levels of education, and are employed or retired. This result motivates the use of age as a covariate in the following analyses. Table 2 describes the differences between women in the five groups in the domains of traumatic experiences, defense mechanisms, and alexithymia by one-way ANCOVAs, with age as a covariate. Table 2. Differences between CH, FM, VU, MIX, and HC groups on TEC, DMRS, and TAS: one-way ANCOVAs.   Chronic Headache (CH) ( n  = 195) M  ± DS Fibromyalgia (FM) ( n  = 186) M  ± DS Vulvodynia (VU) ( n  = 193) M  ± DS Mixed Condition (Mix) ( n  = 315) M  ± DS Healthy Controls (HC) ( n  = 117) M  ± DS Post Hoc F p Partial Eta 2 Traumatic Experience Checklist (Trauma Total) 17.71 ± 1.08 20.50 ± 1.13 18.25 ± 1.13 23.01 ± 0.86 17.39 ± 1.40 MIX > CH, VU, HC 12.710  VU, HC 16.170  VU 10.229  CH 5.953 < .001 0.028  Physical Abuse 1.59 ± 0.24 1.91 ± 0.25 1.81 ± 0.25 2.37 ± 0.19 1.97 ± 0.31 –* 5.149  CH, VU, HC FM > VU, HC 17.128 < .001 0 . 088  Sexual Approach 1.55 ± 0.21 2.00 ± 0.22 2.02 ± 0.22 2.26 ± 0.17 2.04 ± 0.27 –* 4.791 < .001 0.022  Sexual Abuse 0.98 ± 0.18 1.29 ± 0.19 1.19 ± 0.19 1.63 ± 0.15 1.13 ± 0.24 –* 3.298 .003 0.014 Defense Mechanisms Rating Scales (Overall Defensive Functioning; ODF) 5.03 ± 0.03 5.01 ± 0.03 5.03 ± 0.03 4.98 ± 0.03 5.13 ± 0.04 MIX < HC 7.140 < .001 0.035  Mature 40.63 ± 0.82 39.34 ± 0.86 41.87 ± 0.86 39.41 ± 0.65 43.88 ± 1.07 FM, MIX < HC 9.483  VU, HC FM > CH > VU 10.991 < .001 0.056  Immature 35.69 ± 0.69 35.04 ± 0.73 36.51 ± 0.73 36.05 ± 0.55 34.40 ± 0.90 –* 5.588  HC 10.819  HC FM, MIX > CH 17.459 < .001 0 . 090  Difficulty Describing Feelings (DDE) 12.82 ± 0.35 13.09 ± 0.37 12.43 ± 0.37 12.75 ± 0.28 12.55 ± 0.45 –* 7.696  HC 3.044 .006 0.012 *General model is significant with post hoc not significant. Differences between CH, FM, VU, MIX, and HC groups on TEC, DMRS, and TAS: one-way ANCOVAs. *General model is significant with post hoc not significant. In line with the first aim of the study, the differences between women in the five groups in the domains of the total scale of traumatic experiences, MIX scored significantly higher than HC, VU, and CH ( F  = 7.650; df = 4; p  < .001; see Figure 1 ). This trend, indicating a higher presence of traumatic experiences in MIX than other groups, was specifically observed in emotional neglect ( F  = 5.630; df = 4; p  < .001; see Figure 2 ) and emotional abuse ( F  = 3.562; df = 4; p  = .007; see Figure 3 ). Both MIX and FM reported higher scores on bodily threat compared to HC and VU, with no significant difference between MIX and FM ( F  = 9.549; df = 4; p  < .001; see Figure 4 ). Although the general models were significant for physical abuse ( F  = 2.741; df = 4; p  = .028), sexual approach ( F  = 2.307; df = 4; p  = .046), and sexual abuse ( F  = 2.735; df = 4; p  = .028), post hoc tests did not report any significant differences. This may be due to the small effect size in Bonferroni's paired comparisons, causing it to lose significance. Figure 1. Differences between CH, FM, VU, MIX, and HC groups in trauma total scale. Figure 2. Differences between CH, FM, VU, MIX, and HC groups in emotional neglect. Figure 3. Differences between CH, FM, VU, MIX, and HC groups in emotional abuse. Figure 4. Differences between CH, FM, VU, MIX, and HC groups in bodily threat. Differences between CH, FM, VU, MIX, and HC groups in trauma total scale. Differences between CH, FM, VU, MIX, and HC groups in emotional neglect. Differences between CH, FM, VU, MIX, and HC groups in emotional abuse. Differences between CH, FM, VU, MIX, and HC groups in bodily threat. Consistent with the second aim of the study, HC reported significantly higher scores than MIX in the overall domain of defensive functioning ( F  = 7.140; df = 4; p  < .001; see Figure 5 ) and significantly higher scores than MIX and FM in the mature domain ( F  = 9.483; df = 4; p  < .001; see Figure 6 ). Concerning neurotic defense, FM and MIX scored higher than VU and HC, and FM significantly higher than CH, which scored significantly higher than VU ( F  = 10.991; df = 4; p  < .001; see Figure 7 ). Although the general models were significant for immature defense, post hoc tests did not report significant differences. Figure 5. Differences between CH, FM, VU, MIX, and HC groups in overall defensive functioning. Figure 6. Differences between CH, FM, VU, MIX, and HC groups in mature defense. Figure 7. Differences between CH, FM, VU, MIX, and HC groups in neurotic defense. Differences between CH, FM, VU, MIX, and HC groups in overall defensive functioning. Differences between CH, FM, VU, MIX, and HC groups in mature defense. Differences between CH, FM, VU, MIX, and HC groups in neurotic defense. Regarding the last aim of the study, women in the five groups showed differences in the domains of alexithymia. HC scored lower than the other groups on the total scale, indicating less presence of alexithymia ( F  = 10.819; df = 4; p  < .001; see Figure 8 ). In the domain of Externally Oriented Thinking (EOT), HC reported significantly lower scores than FM and MIX ( F  = 3.044; df = 4; p  = .006; see Figure 9 ). For Difficulty Identifying Feelings (DIF), HC again reported significantly lower scores than all other groups, and CH reported lower scores than FM and MIX ( F  = 17.459; df = 4; p  < .001; see Figure 10 ). Although the general models were significant for Difficulty Describing Feelings, post hoc tests did not report any significant differences. Figure 8. Differences between CH, FM, VU, MIX, and HC groups in alexithymia total scale. Figure 9. Differences between CH, FM, VU, MIX, and HC groups in externally oriented thinking. Figure 10. Differences between CH, FM, VU, MIX, and HC groups in difficulty identifying feelings. Differences between CH, FM, VU, MIX, and HC groups in alexithymia total scale. Differences between CH, FM, VU, MIX, and HC groups in externally oriented thinking. Differences between CH, FM, VU, MIX, and HC groups in difficulty identifying feelings.

This study intended to compare some psychological variables in women with different disorders attributed to NP. Previous studies have focused on specific conditions and their psychological characteristics, such as depression, anxiety, catastrophizing, traumatic events, pain acceptance, and sexual functioning, highlighting their role in the onset and worsening of the disorder. However, these studies have always referred to ‘pure’ syndromes (CH, FM, or VU) and not in conditions with multiple NP syndromes in comorbidity (Abu-Arafeh, 2023 ; Chisari et al., 2021 ; Galvez-Sánchez et al., 2019 ; Klonowski et al., 2022 ; Nimbi et al., 2024 ; Thieme et al., 2015 ; Torres-Cueco & Nohales-Alfonso, 2021 ). In this study, it was observed that women with NP syndromes had different profiles, but those with multiple NPs in comorbidity (MIX group) were more impaired overall. The first aim intended to explore possible significant differences in the domain of traumatic experiences in the five groups assessed. In line with our hypothesis, MIX differed overall from the CH, VU, and HC groups, reporting a greater presence of traumatic experiences. The literature proposes the presence of differential risk, suggesting that the impact of stress due to traumatic experiences experienced at different points in childhood may influence the development of different CS syndromes through different etiological pathways (Chandan et al., 2020 ). This has been observed for ‘pure’ syndromes such as FM (Gardoki-Souto et al., 2022 ; Yavne et al., 2018 ), CH (Bottiroli et al., 2018 ; Zamir et al., 2023 ), and VU (As-Sanie et al., 2014 ; Torres-Cueco & Nohales-Alfonso, 2021 ). The present study highlights those patients with more than one NP in comorbidity scored significantly higher, indicating that they experienced more traumatic events during childhood, particularly related to the emotional aspect. In fact, it can be observed that for the domain of emotional neglect, the MIX group differs significantly from the VU group, and for the domain of emotional abuse, there is a significant difference between the MIX and CH groups. Regarding bodily threat, there is a significant difference between MIX, CH, VU, and the healthy control group; moreover, FM is statistically different from the healthy group and VU. In particular, having experienced experiences such as hospitalization and/or intense pain from injuries or operations would seem to be a risk factor for the onset of disorders in which pain is the pivotal symptom, including CP (Battle et al., 2013 ; Kyranou & Puntillo, 2012 ), cancer (Nipp et al., 2018 ), and endometriosis (Liu et al., 2016 ). Interestingly, in addition to MIX, women with FM also differ from other groups in some areas of traumatic experiences. This is confirmed by the existing literature: studies comparing FM and rheumatoid arthritis observed that only patients with FM had significantly higher prevalence rates of all forms of victimization, as well as combinations of adult and childhood trauma, and that maltreatment was found to be an overall risk factor for FM (Hellou et al., 2017 ; Walker et al., 1997 ). A more recent study found that rates of sexual abuse and physical neglect were significantly higher in patients with FM, and thus, physical neglect would be a risk factor for FM (Alciati et al., 2021 ). The results obtained confirm the initial hypothesis: the MIX group differed significantly from the pure conditions and controls in domains related to traumatic experiences. This would seem to indicate that the number and type of emotional events experienced could be associated with painful symptomatologic expression: greater traumatic events related to the emotional sphere (abuse and neglect) could thus lead not only to the onset of painful syndromes but also to the development of more NP syndromes in comorbidity. This could be explained by CS, which is an increased reactivity of nociceptive neurons in the CNS, causing increased sensitivity to normal or subthreshold inputs that would then worsen central nociceptive processing (Arendt-Nielsen et al., 2018 ). Pain would then be aggravated by psychological factors (Sluka & Clauw, 2016 ), such as having experienced traumatic events during childhood. It is, therefore, conceivable that traumatic experiences represent an area that clinicians should focus on. Therefore, working with specific techniques and pathways is essential from a multidisciplinary intake perspective. Regarding the second aim of the present study, we wanted to observe whether there were significant differences between the four groups and the control group regarding overall defensive functioning. Defense mechanisms, a group of automatic and unconscious psychological strategies that mediate reactions to internal or external stressors or emotional conflicts, can be organized hierarchically into levels: the least adaptive ones are the immature defenses, which distort interpersonal reality and are most prominent in personality disorders (Vaillant, 1994 ); neurotic defenses are intrapsychic mechanisms that relate to psychological suffering when used rigidly and inflexibly; finally, the mature defenses, which are more adaptive, are coping strategies and can be used flexibly and sometimes consciously (Vaillant, 1971 ). The results of this study show that, as might have been expected, the healthy group differs statistically from MIX and FM about the use of mature defensive strategies: in fact, HC reports higher scores indicating greater use of this type of defense. Concerning the domain of neurotic defenses, the FM and MIX groups obtained the highest scores, indicative of the higher utilization of neurotic defenses. These two groups differ significantly from VU and HC; in addition, FM differs significantly from CH, which in turn differs from VU. Thus, it may be said that FM is the group that employs neurotic-type defenses the most, right after MIX; these findings add to a still nascent literature on the subject. Few studies are observing the defensive strategies employed in CPs (Di Giuseppe & Conversano, 2022 ; Korkmaz et al., 2020 ; Özsoy & Taşcı, 2021 ): the data in the present study, on the one hand, confirm the most recent findings on FM (Romeo et al., 2022 ) that show significant use of specific non-mature defense mechanisms; and on the other hand contrast with the results of other studies (Landmark et al., 2008 ) that find no differences in defense mechanisms between FM and HC groups. The findings seem to be in line with what has been observed in the literature: the use of mature defenses appears to be associated with control groups, whereas the use of immature defenses is associated with difficult situations and, thus, pathological (Blanco et al., 2023 ; Cramer, 2008 ; Soldz & Vaillant, 1998 ). In fact, those facing a difficult medical condition are more likely to implement more primitive strategies to cope with the resulting negative emotional states. This has also been observed in studies of pain (not NP): increased use of immature defenses has been observed in patients with rheumatoid arthritis (Ramkhelawon et al., 2016 ) and cancer (Di Giuseppe & Perry, 2021 ; Saab et al., 2021 ) the latter in particular employed image distortion defenses. The use of adaptive defenses protects the individual from experiencing stressful conditions of being affected by cancer (Conversano et al., 2020 ; Talepasand & Mahfar, 2018 ), while the use of neurotic and immature defenses is associated with sleep disturbance, worse clinical conditions, and lower survival rates in people with cancer (Hyphantis et al., 2011 , 2016 ). The results of the present study show that the MIX and FM groups differ significantly from the other groups in that they make greater use of neurotic defenses, including intellectualization, isolation of affect, disintegration, displacement, dissociation, reaction formation, and repression; many of these denote an attempt to avoid dealing with the problematic situation. In this regard, an interesting model of pain perception has recently been proposed: avoidance behaviour would be a typical behaviour pattern of people with chronic pain, caused by the immaturity of their defenses and alexithymia, and would cause an increase in the intensity of pain perception (Pahlevan et al., 2019 ). Associated with these considerations, the third aim was to investigate whether there were differences among the five groups considered regarding alexithymia. In general, the control group scored significantly lower than the other groups on the total domain and DIF scale, indicating better emotional identification ability. Moreover, even in the DIF domain, CH scored significantly lower than FM and MIX. Regarding the EOT scale, FM and MIX obtained significantly higher scores than the HC group. Overall, no group scored 61 or higher on the TAS-20, indicating the presence of alexithymic traits. Alexithymia is a highly investigated construct in CPs: recent reviews show that these patients have a higher prevalence of alexithymia, particularly in the DIF domain (Aaron et al., 2019 ; Di Tella & Castelli, 2016 ) and that FM patients have substantially higher alexithymia than other CP syndromes (Habibi Asgarabad et al., 2023 ). As noted above, the combination of immature defenses and high levels of alexithymia, particularly in the DIF and EOT domains, may indicate a defense against painful emotional content, and this is observed in both the FM and MIX groups, which differ significantly from the other groups. From a clinical point of view, women with high levels of alexithymia and high use of neurotic defenses may be at risk of developing CP or worsening an already present pain condition because they are unaware of their emotional experiences. This could lead to increased psychological distress and predispose them to an unhealthy lifestyle. Thus, the interplay between psychological and organic aspects should be explored, considering the mutual influence of different aspects of psychological functioning on the course of CP disease, including traumatic exposure, defensive functioning, and alexithymia (Di Giuseppe & Conversano, 2022 ; Yoo & Ryff, 2019 ). Psychological factors have been demonstrated to interact with and contribute to the onset or exacerbation of chronic pain. It is imperative that a therapeutic approach that acknowledges these interconnections is employed in order to ensure the effective treatment of patients suffering from chronic pain and alexithymia. Considering these patients’ experiences and emotional responses is an essential component of their care. This information is relevant to the treatment outcome as it can improve case formulation and aid in tailoring specific interventions to achieve changes in psychological and pain symptoms. The findings of this study indicated the necessity to extend our focus beyond the psychological factors investigated in this study, as only through meticulous preliminary screening can we comprehensively assess the individual patient's requirements. The delivery of psychological treatments should be tailored to the individual, incorporating trauma-focused therapies and interventions designed to enhance emotional awareness and processing. Furthermore, treatment should be comprehensive, combining a psychological approach and physical rehabilitation, as such an intervention could lead to positive outcomes for patients with CP. As previously mentioned, patients suffering from NP must be cared for by a coordinated multidisciplinary team. In order to provide holistic care that addresses the psychological and physiological aspects of NP syndromes, the patient must be cared for by a team of healthcare professionals, including psychologists and pain specialists. The role of the psychologist is pivotal in the management of NP syndromes. The psychologist must comprehend the patient's emotional needs and establish patient-centered communication to develop a therapeutic alliance and ensure the efficacy of treatments. Furthermore, the emotional responses of the therapist may, in fact, alleviate symptoms of psychological distress, potentially leading to an improved disease course and quality of life (Yonatan-Leus et al., 2021 ). The present study also has some limitations: questionnaire administration was conducted online, using snowball sampling for survey dissemination. Although the cohort of women was reached through patients’ associations, the etiopathogenesis of CP was not verified through direct diagnostic tests but only self-reported by the participants; the protocol only included self-report questionnaires. Future studies should supplement these measures with direct physical assessments and in-person interviews; the choice of a web-based survey may have limited the participation of women less familiar with technology. questionnaire administration was conducted online, using snowball sampling for survey dissemination. Although the cohort of women was reached through patients’ associations, the etiopathogenesis of CP was not verified through direct diagnostic tests but only self-reported by the participants; the protocol only included self-report questionnaires. Future studies should supplement these measures with direct physical assessments and in-person interviews; the choice of a web-based survey may have limited the participation of women less familiar with technology. Furthermore, it is crucial to delineate the potential directions in which future research may develop. As the present study is a cross-sectional research design, future longitudinal studies should be considered to conduct research that can explore the causal relationships between traumatic experiences, alexithymia, defense mechanisms, and the development of NP syndromes. Furthermore, with a bio-psycho-social approach in mind, the neural pathways linking alexithymia to emotional processing deficits in NP patients should be examined to inform the development of targeted treatment. Finally, other psychological variables should be investigated since, as highlighted above, studies to date have referred to ‘pure’ CP syndromes and not in conditions with multiple NP syndromes in comorbidity. In particular, psychological variables that we suggest should be studied include catastrophizing, beliefs about pain, personality traits, and emotional regulation.

This study provides information on psychological factors related to CP conditions in women, including CH, FM, VU, and MIX. Results indicate that traumatic experiences, particularly emotional neglect and physical threats, may contribute to the development and worsening of multiple CP conditions, especially in individuals with comorbidities. Furthermore, variations in defensive functioning underline the importance of adaptive defense strategies in managing CP. The FM and MIX groups show a greater tendency towards neurotic defenses. In addition, the existence of alexithymia, especially in FM and MIX participants, underlines the impact of emotional processing difficulties on the manifestation of CP. It is, therefore, possible to conclude that since MIX has worse symptomatology, psychological aspects are particularly relevant in this type of patient. Moreover, as each person deals with pain differently and therefore, from the point of view of personalized medicine, it is important to delve into the psychological profile of each patient during the assessment phase. In this way, it is possible to understand the impact of psychological factors and, thus, the importance of psychological treatment and psychotherapy.