Vitamin D Deficiency May Contribute to the Reduction of Sympathetic and Sensory Innervation in Arthritis

Vitamin D Deficiency May Contribute to the Reduction of Sympathetic and Sensory Innervation in Arthritis

A new study published in Neuroscience demonstrates that vitamin D deficiency in experimental animals is related to sensory and sympathetic denervation and reduced neurotrophin levels in the synovium.

Several studies have associated vitamin D levels with rheumatoid arthritis (RA) development in humans. Thus, low vitamin D levels are documented in patients with active RA. Also vitamin D levels inversely correlate with the activity, pain scores and disabilities profiles in RA, whereas vitamin D supplementation delays the onset and progression of arthritis models in rodents (MT Cantorna et al., 1998).

However, little is known as to the mechanism of how vitamin D influences RA development. Of note, vitamin D can bind to receptors located in sensory and sympathetic neurons, possibly affecting joint homeostasis and innervation. Also, partial degeneration of sympathetic and sensory synovial axons is observed in RA patients and in the early phases of many rodent inflammatory arthritis models. In addition, previous research indicates that this innervation also is important to the regulation of immune cells.

In the Neuroscience study SE Tague and PG Smith, from the University of Kansas Medical Center, Kansas City, KS, USA, analyzed the density of synovial nerve fibers in ovariectomized rats on a vitamin D-deprived diet. The authors showed that 4 weeks of vitamin D deprivation decreased sensory and sympathetic innervation in rat synovium.

Of note, vitamin D deficiency also reduced the levels of neurturin, a potent neurotrophic factor, in synovial mast cells. This suggests a role in nerve nurturing, as mast cells are well known to be in an intimate contact with synovial nerves fibers (M Hukkanen et al., 1991).

The study of Tague & Smith suggests that vitamin D deficiency may increase arthritis onset and development via reduction in synovial innervation and neurotrophin levels. It may also indicate that a simple vitamin D monitoring program and supplementation in inflammatory diseases such as rheumatoid arthritis could be useful as a complement to the actual anti-inflammatory therapies.

Source: Neuroscience, 2014, 279: 77-93. doi: /10.1016/j.neuroscience.2014.08.035
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Source: Cover Image: Sympathetic nerve fibers (depicted in red) are shown to wrap around the pain-sensing neurons (green) in the joint synovium of arthritic animals. Credit: Geraldine Longo, McGill University.

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