Pathophysiology of musculoskeletal pain: a narrative review

Pathophysiology 1

Goal of the Study?

In this paper, [Pathophysiology of musculoskeletal pain: a narrative review], the authors provide a review of the various pathophysiology mechanisms of musculoskeletal pain and how they interact to promote the transition from acute to chronic pain. 


Why are they doing this review?

Chronic musculoskeletal pain is defined as pain felt in the musculoskeletal tissues that last for more than 3 months and is characterized by functional disability and emotional distress. It is a secondary type of pain caused by different conditions such as infection or auto-inflammatory processes that lead to systemic inflammation or structural changes to joints, muscles or tissues. 

Chronic musculoskeletal pain is prevalent in the general population, with approximately 37% of the US population impacted and an economic burden of $635 billion per year. Outside of the US, the prevalence ranges from 18.6% in Switzerland to over 45% in Italy and France.


What did they find?

In the review, the authors illustrate how many factors and processes interact to produce musculoskeletal pain. Research illustrates that bones, joints and muscles, including the ligaments, capsules and menisci, are innervated by a network of sensory nerve fibres including, Aδ and C fibres. These fibres’ stimulation can drive musculoskeletal pain through mechanical distortion, local acidosis, and increased bone medullary pressure. This then drives the promotion of inflammatory mediators such as nerve growth factor (NGF), pro-inflammatory cytokines interleukin (IL) 1ß, IL-6, tumour necrosis factor- α chemokines. Moreover, the interaction between immune and nervous systems and glial stimulation further promotes these inflammatory mediators that magnify and sensitize pain signals and lead to cortical remodelling.

Bone pain can also be caused by the increase in sensory nerve fibres where there are injuries. During bone healing, nerves sprout around the injury site and then pull back when it is healed. However, when bones don’t heal (as in osteoarthritis), the injured area remains hyper-innervated, and heightened pain sensitivity occurs. 

Finally, research has indicated that sex, age, psychosocial factors, beliefs and thoughts influence gene expression and the experience of musculoskeletal pain. For example, women experience higher pain sensitivity than men and have a different biologic response to tissue damage with higher cytokine production than men, which means a stronger inflammatory response and higher pain levels. 


Why do these findings matter?

Understanding the pathophysiology of musculoskeletal pain, which includes biological and demographic and psychological factors, is critical to developing pain management treatments and strategies for patients.

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