10 Barca et al.
“endogenous opioid system”—involved in reward and the regu-
lation of pain and affect—have been documented (Bresin and 
Gordon 2013), as low basal plasma levels of β-endorphins (which 
are peripherally released following tissue damage) in psychiatric 
patients (van der Venne et al. 2021, Cakin Memik et  al. 2023). 
Lower salivary levels of β-endorphins have also been registered 
immediately before NSSI, compared to post-NSSI (Störkel et al. 
2021). Thus, an imbalance in the opioid system might be a rel-
e
vant component in NSSI, where self-injures might be acted 
to initiate the release of β-endorphins to restore homeostasis
(Stanley et  al. 2010 , Bresin and Gordon 2013). Another line 
of research examined “nociceptive dysregulation,” with possible 
hypoalgesia (Kirtley et al. 2016), showing higher pain thresh-
olds and lower pain intensity in adolescents with NSSI (Nock 
et al. 2006, 2009, v
an der Venne et al. 2021). Recent works failed 
to replicate these findings but reported specific alterations in 
descending inhibitory pain control (Leone et al. 2021, Lalouni 
et al. 2022). Despite some inconsistencies, this is an area that 
is worth further investigation. It remains to investigate to what 
extent the perspective on NSSI offered here could be extended to 
cover the aforementioned body of evidence and whether active 
inference could help integrate the different perspectives we have
discussed.
We focused on adolescence as a potentially critical period for 
NSSI, given that it is associated with high levels of uncertainty 
about several central domains in human life. However, there 
are other (gender-related) developmental periods in which bod-
ily changes might be coupled with increased levels of uncertainty 
(e.g. in physiology, in the sense of self, in the social role) and vulner-
ability. Pregnancy and transition to menopause, e.g. are periods of 
endocrine and hormonal upheavals that might impact a woman’s 
affective life and well-being. These physiological changes are cou-
pled with a fundamental developmental transition that requires a 
redefinition of personal identity and narrative integration (McLean 
and Lilgendahl 2019 ), with increased uncertainty of one’s inter-
nal states and role in the social context. Taking into account 
the perimenopausal and menopausal transition, the physiologi-
cal, psychological, and affective experiences associated with it are 
very heterogeneous. Some women might experience it as a new 
beginning, whereas for others, it may be more critical (Deeks 2003). 
In some cases, e.g. the menopause transition might perturb the 
continuity of one’s sense of self, inducing discrepancies in inter-
nal self-coherence (e.g. the end of childbearing years, the aging 
process), which might increase the level of distress (Barca and De 
Marchis 2018).
The dramatic changes that a women’s physiology undergoes 
during life have been suggested to concur with the atypical 
interoception often reported (e.g. heightened interoceptive atten-
tion but poor interoceptive accuracy), which might contribute 
to their greater vulnerability to mental illness (Murphy et al. 
2019). Although this is still a speculative hypothesis that needs 
to 
be tested empirically, the effect of these transition periods on 
women’s well-being is currently overlooked and deserves more 
attention.
Finally, although we only focused on “maladaptive” strate-
gies to modify the sense of self through bodily sensations, there 
are also “adaptive” strategies that use the body to improve the 
sense of self and feelings of well-being. Among these, e.g. is 
engaging in physical activities to reduce emotional distress. Per-
forming physical activity concurs in the reduction in symptoms 
of depression and anxiety, acting on both psychological (e.g. 
diverting from unpleasant stimuli or increasing the sense of self-
efficacy) and physiological mechanisms (e.g. through the release