Vitamin D and Chronic Pain
What is it?
■ Fat soluble vitamin (remember ADEK)
■ prohormone: not active, has to be converted to 1,25 – D (AKA calcitriol) to be used in
the body
■ 2 major forms: D2 and D3: D3 is produced in skin exposed to sunlight, D2 is produced
by fungus and plants in response to UV radiation – both forms used for human nutritional
supplementation
What does it do?
■ Regulates calcium and phosphorus levels
-reabsorption of calcium in kidneys
-promotes absorption from intestines
-bone growth and remodeling by osteoclasts and osteoblasts
- inhibits PTH secretion
■ Immunomodulation
-VDRs found in most immune cell types (monocytes, macrophages, NK cells, T
cells, and B cells) and activation of this receptor by hormonally active vitamin D has antiproliferative, anti –differentiative properties promoting an increase in activity of natural
killer cells and macrophage phagocytosis
-increases production of antimicrobial peptide (cathelicidin) when macrophages
come into contact with bacteria and viruses
-suppress T cell activation, effects cytokine secretions
-affects maturation, differentiation and migration of dendritic cells
■ Anti-tumor activity
- via role as nuclear transcription factor that regulates cell growth,
differentiation and apoptosis
What are normal levels?
Measured as 25-hydroxy vitamin D
0-15 ng/mL – severely deficient
15-32 ng/mL – mildly deficient
32-100 ng/mL – optimal
>100 ng/mL – toxicity possible
What problems are associated with Vitamin D deficiency?
-bone softening/bone pain
-osteomalacia and/or osteoporosis in adults
-rickets in children
-hypertension
-TB
-cancer
-dental disease
-MS (onset in those predispositioned)
-chronic pain
-Parkinson’s disease
-cognitive impairment
What causes deficiency?
-inadequate intake via natural sources: egg, fish, mushrooms, beef liver
-inadequate sunlight exposure
-disorders that limit absorption
-impaired conversion to hormonally active form
Does hypovitaminosis D have any implications for chronic pain patients?
Fairly new topic of interest in pain
■ Review article in J AM Board of Fam Med 2009, showing improvement of
chronic back pain in pts with “failed back” dx after vitamin D repletion
-idea that vitamin D is required for differentiation, proliferation, and
maturation of cartilage cells and for the production of proteoglycan synthesis in articular
chondrocytes
-noted that muscle pain and myopathy resolved faster than bone pain (4
weeks vs 1 year)
■ Article from Aukland Regional Pain Service, 2009, discussing the role of glial
cells and their influence on neural function in postherpetic neuralgia. Schwann cells are
thought to be part of the mechanism of pain in PHN and vitamin D reduces glial
inflammation
■ Prospective observational study in Archives of Internal Medicine, 2008, looking
at 51 pts with T2DM and neuropathic pain, vitamin D levels were drawn and if less than
24 ng/mL, they were repleted. Reevaluation in 3 months showed pain scores
significantly reduced (-48.5% and -39.4% in two different pain score scales.)
■ Topical review article in Pain, 2008. Discussed role of vitamin D and chronic
pain. Found that the presently available evidence did not allow them to conclude that
vitamin D is relevant to chronic pain. Required better evidence, specifically large, double
blind RCTs.
What to measure (what to order at Vandy)?
-blood calcidiol level (25-hydroxy-vitamin D)
-red top tube
-“send off lab”
How to replete?
-1000 IU/day will increase levels by 20-25 nmol/L
-2000 IU/day will increase levels by 40-50 nmol/L
Take home message for us:
- Even though there may not be enough appropriate evidence to say that vitamin D
repletion causes statistically significant improvement in chronic pain, clinically, there are
patients that have had improvement in their pain levels and it could be a recommendation
that we give to referring doctors