Blackmores Institute

While Vitamin D is known for its fundamental role in calcium homeostasis and bone metabolism, a 2020 review highlights the important role it may also play in modulating and relieving pain(2).­<table> <tr><td> Key study information - Vitamin D deficiency is correlated with general and specific pain ­ - Supplementation may reduce pain with increasing vitamin D blood levels - The mechanism of action is not fully understood ­ - Vitamin D mediates gene expression involved in pain signalling ­ - May influence pain indirectly or directly through modulation of: o Gut microbiota o Immune and inflammatory mediators and neurochemicals o Epidermal and nerve factors and receptors o Cannabinoid and opioid receptors </td></tr> </table>Vitamin D and pain research Vitamin D deficiency studies show a strong correlation between vitamin D levels and musculoskeletal pain, such as lower back pain, with a significant association in painful diabetic peripheral neuropathy. Several clinical trials have also reported links between low vitamin D levels and general pain or pain following an injury. Other research reported progressive worsening of pain as vitamin D levels declined. Conversely, supplementation to increase vitamin D levels reduced pain. Although there are known associations between vitamin D and pain management, the authors of this review explain that while it is not fully understood how vitamin D modulates pain, the review outlined potential mechanisms.The potential mechanisms in pain regulationThe mechanism of action for Vitamin D extends beyond a nutritional function. Vitamin D is actually a hormone. After being converted in the body into its biologically active form, it interacts with multiple vitamin D receptors (or VDRs) to mediate gene expression. Many of these genes encode for proteins involved in pain signaling pathways, with VDRs found across the tissues involved in pain sensing, processing, perception and modulation. Pain signaling pathways are complex. Among other actions, vitamin D may directly or indirectly modulate: • Gut microbiota – they produce short-chain fatty acids and neurotransmitters involved in pain signaling, with dysbiosis causing inflammation that can lead to visceral pain • Cytokines, neurochemicals and other inflammatory mediators released during inflammation and injury • Expression of epidermal and nerve factors and receptors with key roles in pain signaling • Cannabinoid and opioid receptorsFurther research will increase the understanding of the actions and benefits of vitamin D, especially its potential to be an important treatment option for the management of chronic pain. Source:(1) Vos T, et al.: Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries,1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1211-59. <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32154-2/fulltext">DOI: 10.1016/S0140-6736(17)32154-2</a>(2). Habib AM, et al.: Vitamin D and its potential interplay with pain signaling pathways. Front Immunol. 2020;11:820. <a href="https://www.frontiersin.org/articles/10.3389/fimmu.2020.00820/full">DOI: 10.3389/fimmu.2020.00820</a>

Chronic pain is now the leading cause of disease burden globally(1). Around 20% of those suffering pain, derive no benefit from analgesics with most current treatment protocols managing, not curing, pain.

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