Association between cortisol levels and pain threshold in systemic sclerosis and major depression

Abstract

Pain perception and threshold show complex interactions with the inflammatory, psychiatric and neuroendocrine stimuli. This study aims to test whether lower serum cortisol levels are associated with lower pain thresholds and higher degree of depression in systemic sclerosis (SSc) and major depression with atypical features (MD-AF) patients compared to controls. 180 female subjects (SSc = 60, MD-AF = 60, healthy controls = 60) participated in this observational, cross-sectional, parallel group study. Pressure pain threshold (PPT) was assessed in three anatomical sites: nail bed (NB), metacarpophalangeal joint (MCP) and quadriceps muscle (QDR). Depressive symptoms were evaluated using the Beck Depression Inventory (BDI) scale and morning serum cortisol levels were collected. In SSc patients, quality of life was measured through the Health Assessment Questionnaire (HAQ-DI) and the scleroderma-specific visual analogue scales (scleroderma-VAS). Lower PPT scores (NB 4.42 ± 1.6; MCP 4.66 ± 1.4; QDR 4.79 ± 1.5) were observed in SSc patients compared to both MD-AF (NB 7.33 ± 2.2; MCP 6.01 ± 1.9; QDR 6.31 ± 1.6; p < 0.005) and controls (NB 9.57 ± 2; MCP 7.9 ± 2.1 and QDR 8.43 ± 2.1; p < 0.0001), while MD-AF patients had lower PPT scores compared to controls (p < 0.0001). SSc patients had also lower serum cortisol levels compared to MD-AF patients (8.78 vs 13.6 μg/dl; p < 0.05). A direct correlation was observed between serum cortisol and PPT scores both in SSc (r for NB 0.29; for MCP 0.25; for QDR 0.27) and in MD-AF (r for NB 0.34; for MCP 0.25; for QDR 0.47; p < 0.05), while depressive symptoms negatively correlated with serum cortisol (r for NB 0.34; for MCP 0.17; for QDR 0.15) and in MD-AF (r for NB 0.19; for MCP 0.31; for QDR 0.30; p < 0.05). Among SSc patients, those with serum cortisol levels below the normal range (n = 16) had higher BDI scores (15, 6-21 vs 9, 2-15; p < 0.005), lower PPTs (NB 4 ± 1.4 vs 4.9 ± 0.9; MCP 4.1 ± 0.8 vs 4.8 ± 0.9; QDR 4.1 ± 1.2 vs 5 ± 0.9; p < 0.005) and higher HAQ-DI (1.25, 0.25-2 vs 0.75, 0-1.25; p < 0.05) and scleroderma-VAS scores (VAS overall severity 7, 5.5-9.5 vs 4.5, 2.5-6; p < 0.05). The effect of cortisol serum levels upon pain mechanism, in chronic inflammatory conditions warrants longitudinal studies to detect treatable variations in pain thresholds, depressive symptoms and to improve quality of life.

The aetiology of social deficits within mental health disorders: The role of the immune system and endogenous opioids

“…There is a lower pain threshold (PT) in depressed patients ( Adler and Gattaz, 1993 ; Marazziti et al., 1998 ) compared to their non-depressed counterparts. Though, PT differences in depressed patients are modality-specific: PT is increased for electric and heat-based pain, but reduced in ischemic pain ( Bagnato et al., 2018 ; Bär et al., 2005 ; Thompson et al., 2016 ). The difference in threshold between pain modalities could be because different pain modalities are related to different types of opioid receptors ( Scherrer et al., 2009 ).…”

Toward Composite Pain Biomarkers of Neuropathic Pain—Focus on Peripheral Neuropathic Pain

“…Cortisol is a proposed stress-related pain biomarker ( 125 ). DHEA and DHEAS are neurosteroids that modulate inhibitory GABA receptors and excitatory NMDA receptors, producing complex neuronal effects ( 126 ).…”

The aetiology of social deficits within mental health disorders: The role of the immune system and endogenous opioids

“…There is a lower pain threshold (PT) in depressed patients (Adler and Gattaz, 1993;Marazziti et al, 1998) compared to their non-depressed counterparts. Though, PT differences in depressed patients are modality-specific: PT is increased for electric and heat-based pain, but reduced in ischemic pain (Bagnato et al, 2018;B€ ar et al, 2005;Thompson et al, 2016). The difference in threshold between pain modalities could be because different pain modalities are related to different types of opioid receptors (Scherrer et al, 2009).…”