Vaginismus is an involuntary muscle contraction of the outer third of vaginal barrel causing
sexual penetration almost impossible. It is generally classified under sexual pain disorder (SPD).
In Diagnostic and Statistical Manual, 5th edition (DSM-5), it is classified under the new rubric of
Genito-Pelvic Pain/Sexual Penetration Disorder. This fear-avoidance condition poses an ongoing significant
challenge to the medical and health professionals due to the very demanding needs in health
care despite its unpredictable prognosis. The etiology of vaginismus is complex: through multiple biopsycho-
social processes, involving bidirectional connections between pelvic-genital (local) and higher
mental function (central regulation). It has robust neural and psychological-cognitive loop feedback
involvement. The internal neural circuit involves an inter-play of at least two-pathway systems, i.e.
both “quick threat assessment” of occipital-limbic-occipital-prefrontal-pelvic-genital; and the chronic
pain pathways through the genito-spinothalamic-parietal-pre-frontal system, respectively. In this review,
a neurobiology root of vaginismus is deliberated with the central role of an emotional-regulating
amygdala, and other neural loop, i.e. hippocampus and neo-cortex in the core psychopathology of
fear, disgust, and sexual avoidance. Many therapists view vaginismus as a neglected art-and-science
which demands a better and deeper understanding on the clinico-pathological correlation to enhance
an effective model for the bio-psycho-social treatment. As vaginismus has a strong presentation in
psychopathology, i.e. fear of penetration, phobic avoidance, disgust, and anticipatory anxiety, we
highlighted a practical psychiatric approach to the clinical management of vaginismus, based on the
current core knowledge in the perspective of neuroscience.