| (i) Vitamin D as a neuroactive steroid modulates neuronal excitability and brain neurotransmitters and activates a variety |
| of signal transduction systems |
| (ii) Vitamin D influences prostaglandin action by inhibiting COX-2 expression and by stimulating 15-prostaglandin |
| dehydrogenase (15-PGDH) expression that degrades prostaglandins that would have lowered the firing |
| threshold of sensory neurones |
| (iii) Vitamin D inhibits synthesis of nitric oxide synthase (iNOS), the enzyme that produces nitric oxide (NO, |
| a neurotransmitter involved in nociceptive process that contributes to development of central sensitization) |
| in macrophages that activate microglia and astrocytes |
| (iv) VDR, 1α-hydroxylase, and vitamin D binding protein in the hypothalamus are suggested as mechanism by which |
| Vitamin D deficiency is implicated in pathophysiology of various primary headache disorders |
| (v) Vitamin D upregulates synthesis of neurotrophins affecting development, maintenance, and survival of neurones |
| (vi) Vitamin D affects a number of inflammatory pathways associated with chronic pain by upregulating transforming |
| growth factor beta 1 (TGF-β1) in astrocytes and microglia that suppresses activity of various cytokines |
| (vii) Vitamin D suppresses tumour necrosis factor alpha (TNF-α) and macrophage colony-stimulating factor (M-CSF) in |
| astrocytes and microglia and inhibits pain pathways |
| (viii) Vitamin D inhibits T-helper cell over activity and plays an important role in preventing autoimmune diseases |
