1. 2019;22;E191-E203Gender Differences in the Association of Brain Gray Matter and Pain-Related Psychosocial Characteristics
   Observational Study
   Anneleen Malfliet, PhD, Robby De Pauw, MSc, Jeroen Kregel, PhD, Iris Coppieters, PhD, Mira Meeus, PhD, Nathalie Roussel, PhD, Lieven Danneels, PhD, Barbara Cagnie, PhD, and Jo Nijs, PhD.

BACKGROUND: Although the association of gray matter morphology alterations and pain-related psychosocial characteristics with pain intensity and chronification in people with chronic spinal pain is evident, research on their mutual interaction is scarce and does not account for possible gender differences. Gender-based differences are, however, of utmost importance to consider when examining pain neurobiology.

OBJECTIVES: To look for gender differences in the association between magnetic resonance imaging- (MRI) derived brain gray matter morphology and self-reported psychosocial characteristics.

STUDY DESIGN: An explorative, observational study.

SETTING: University Hospitals Ghent and Brussels, Belgium.

METHODS: Brain gray matter morphology (using MRI) and self-reported psychosocial characteristics were examined in women and men with nonspecific chronic spinal pain. Statistical analyses were performed in SPSS and R to identify differences between men and women regarding brain gray matter, self-reported psychosocial characteristics, as well as gender differences in the association between those outcome measures.

RESULTS: A total of 94 people with chronic spinal pain were studied, including 32 men (15 suffering from neck pain, 17 suffering from low back pain; demographics [mean ± SD] age: 45.00 ± 12.02 years; pain duration: 128.37 ± 110.45 months), and 62 women (36 suffering from neck pain, 26 suffering from low back pain; demographics [mean ± SD] age: 38.78 ± 12.69 years; pain duration: 114.27 ± 92.45 months). Woman showed larger (positive) associations of several central brain areas (paracentral, precentral, postcentral, etc.) with perceived consequences (P < 0.001), emotional representations (P < 0.001), chronicity (P < 0.001), and pain catastrophizing (P< 0.001). Men showed larger (both positive and negative) associations of the precuneus cortex, the precentral gyrus, and the insula with perceived personal control (P < 0.001) and kinesiophobia (P < 0.001).

LIMITATIONS: Other factors, such as menstrual cycle and medication can have a certain influence, and were only partly taken into consideration in the present investigation to obtain sufficient power. Another limitation is the observational study design, which hampers the possibility to look for causal or temporal interactions.

CONCLUSIONS: Gray matter morphology relates differently to psychosocial characteristics in women and men. These explorative findings provide ideas for further research to investigate if targeting perceived negative consequences of the illness, perceived emotional representations, perceived chronicity, and pain catastrophizing in women, and perceived personal control of the illness and kinesiophobia in men, could contribute to the normalization of brain alterations in people with nonspecific chronic spinal pain.

KEY WORDS: Gray matter, brain morphology, central nervous system, illness perceptions, central sensitization