Altered BDNF Methylation in Patients with Chronic Musculoskeletal Pain and High Biopsychosocial Complexity

Figures & data

Table 1 Clinical Characteristics of the Participants

Characteristics	Patients (N=58)	Controls (N=18)
Age (years)	41 (13)	40 (11)
Sex F (percent)	12 (21%)	7 (39%)
BMI	27 (5)	24 (3)**
Time since injury (median in days)	436 (39–5331)	–
DN4 ≥4	11 (18%)	–
Pain location		–
– Upper limb	18 (31%)
– Lower limb	27 (47%)
– Back	11 (19%)
– Polytrauma	2 (3%)
INTERMED Score (0–60)	20.6 (6.2)	–
BPI (0–10)	4.6 (2.0)	–
HADS anxiety (0–21)	8.6 (4.5)	–
HADS depression (0–21)	6.7 (4.0)	–
TSK (17–68)	42.8 (8.2)	–
PCS (0–52)	19.4 (11.4)	–
CIRS (0–56)	4.1 (2.5)	–

Notes: The values are expressed as mean (standard deviation), median (range) or number (%); **p<0.01.

Abbreviations: BMI, body mass index; DN4, Douleur Neuropathique en 4 Questions; BPI, Brief Pain Inventory; HADS, Hospital Anxiety and Depression Scale; TSK, Tampa Scale of Kinesiophobia; PCS, Pain Catastrophizing Scale; CIRS, Cumulative Illness Rating Scale.

Table 2 Correlations Between the Average CpG Methylation Values and the Independent Variables

	Spearman Correlation Coefficient	95% Confidence Interval
INTERMED score	−0.40**	−0.65 to −0.10
Time since injury	−0.12	−0.39 to 0.16
BPI	−0.11	−0.40 to 0.17
TSK	0.11	−0.13 to 0.35
HADS anxiety	−0.06	−0.33 to 0.21
HADS depression	−0.04	−0.30 to 0.22
PCS	−0.02	−0.29 to 0.21

Notes: **p<0.01, n=58.

Abbreviations: BPI, Brief Pain Inventory; TSK, Tampa Scale of Kinesiophobia; HADS, Hospital Anxiety and Depression Scale; PCS, Pain Catastrophizing Scale.

Figure 1 Average CpG methylation values of controls and CMSP patients. ***p<0.005, n = 18 controls and 58 patients.

Table 3 Average CpG Methylation Values of the BDNF Multivariate Analysis Model

Outcome	Variable	Regression Coefficient (95% CI)	p-value
BDNF CpG	INTERMED score	−0.004 (−0.008 to −0.001)	0.02*
	Age	0.000 (−0.001 to 0.003)	0.43
	Sex	0.041 (−0.001 to 0.097)	0.14
	CIRS	−0.008 (−0.018 to 0.002)	0.13

Notes: *p<0.05, n=58.

Abbreviations: BDNF, brain-derived neurotrophic factor; CIRS, Cumulative Illness Rating Scale; CI, confidence interval.