Oversensitive Sensory Neurons Can Cause Joint Deformities – But It Can Be Treated

Joint Pain Spine

Arthrogryposis, also known as joint contractures, is a condition that results in multiple joint deformities. It is characterized by the inability to move a joint, resulting in a fixed, bent position. This can affect any joint in the body but is most commonly seen in the arms, legs, and spine.

According to a recent study, an overabundance of mechanosensation in the neurons responsible for our sense of limb position in space can disrupt musculoskeletal development and cause joint deformities such as arthrogryposis.

The research also demonstrates that it is possible to treat certain musculoskeletal conditions non-invasively by reducing this heightened sensory neuronal activity during a crucial age through the use of Botox or a specialized diet.

Distal arthrogryposis (DA) is a disorder characterized by congenital joint deformities, or contractures, that often restrict movement in the hands and feet and is estimated to afflict roughly one in 3,000 individuals worldwide. Alleviating the symptoms often requires invasive surgeries.

Although mutations in genes associated with muscle and joint function have been linked to DA, gain-of-function mutations in PIEZO2 – a principal mechanosensor in sensory neurons that underlies touch sensation, proprioception, and other mechanosensory processes – have been found in patients with DA subtype 5 (DA5).

However, the mechanism by which PIEZO2 mutations cause DA is unknown. Using a mouse model, Shang Ma and colleagues found that over-expression of the mutant Piezo2 gain-of-function allele in proprioceptive neurons that enervate muscles and tendons during a critical postnatal period during development can cause joint contracture. These defects were not caused when the dysfunctional allele was expressed in skeletal muscles, cartilage, or tendons.

According to Ma et al., Botox injection and a dietary fatty acid commonly found in fish reduced joint and tendon defects.

“The study by Ma et al. provides exciting new insights into the mechanisms that cause DA,” writes Urich Müller in a related Perspective. “Finding that expression of the gain-of-function allele of Piezo2 in young adult mice does not cause DA symptoms is reassuring. It narrows down a time window for potential therapeutic intervention that could lead to lifelong improvement for the affected patients.”

Reference: “Excessive mechanotransduction in sensory neurons causes joint contractures” by Shang Ma, Adrienne E. Dubin, Luis O. Romero, Meaghan Loud, Alexandra Salazar, Sarah Chu, Nikola Klier, Sameer Masri, Yunxiao Zhang, Yu Wang, Alex T. Chesler, Katherine A. Wilkinson, Valeria Vásquez, Kara L. Marshall and Ardem Patapoutian, 12 January 2023, Science.
DOI: 10.1126/science.add3598

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