Table 4.

Summary of findings (GRADE).

Spinal manipulation compared to Control/Sham in influencing neuropeptides and inflammatory biomarkers
Patient or population: Healthy or symptomatic participants Settings: Primary care, outpatient, communityIntervention: Spinal ManipulationComparison: Control/sham
Quality assessment							№ of patients		Effect
№ of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Spinal Manipulation	Control	Relative(95% CI)	Absolute(95% CI)	Quality
Substance-P, immediate changes (assessed with blood)
3	randomised trials	not serious	not serious	not serious	very serious¹	none	56	69	-	SMD 0.71 lower(1.22 lower to 0.22 lower)	⊕⊕°°LOW
Substance-P, short-term changes (assessed with blood)
2	randomised trials	not serious	serious²	not serious	serious³	none	44	60	-	SMD 1.16 fewer(2.53 lower to 0.21 higher)	⊕°°°VERYLOW
Neurotensin (assessed with: Blood)
2	randomised trials	not serious	not serious	not serious	very serious⁴	none	33	35	-	SMD 0.52 lower(1.01 lower to 0.03 lower)	⊕°°°VERYLOW
Oxytocin (assessed with: Blood)
2	randomised trials	not serious	not serious	not serious	very serious⁴	none	33	35	-	SMD 0.47 lower(1 lower to 0.06 higher)	⊕°°°VERYLOW
Orexin-A (assessed with: Blood)
2	randomised trials	not serious	not serious	not serious	very serious⁴	none	33	35	-	SMD 0.47 lower(1 lower to 0.06 higher)	⊕°°°VERYLOW
Inflammatory Biomarkers (TNF, IL-2; assessed with: Blood)
4	randomised trials	not serious	serious 5	not serious	not serious	none	107	85	-	See comment	⊕⊕°°LOW

Note: CI: Confidence interval; SMD: Standardised mean difference

¹Graphical data retrieved using software and SD imputed.

²Heterogeneity = 86%

³Sample size < 100. Findings based on single study.

⁴Sample size < 100

⁵Known Heterogeneity, studies not pooled