Granada, Nicaragua
Monday 22nd December 2014

In this series of articles, I am investigating the impact that temporomandibular joint dysfunction (TMJD) can have on the physical & physiological wellbeing of an athlete as well as how we can manage TMJD.

What I started to discuss in the previous two posts & will continue to investigate in this post, is whether or not TMJD could impact the physiological ability of joints, tendons, ligaments & other collagenous structures to respond to load & recover from injury.

In the first instance, I established that a link between TMJD & the composition of connective tissue exists, with this relationship having a subsequent impact on injury rates in sportsmen & women.  During the second article, I concentrated on how elevated systemic substance P levels that occur in response to TMJD could potentially influence the response of tendon tissue to acute loading, injury & remodelling. In this post, I am going to discuss the possible pathways that are at work in cases of ligament & joint damage.

To recap, the basis of the link between TMJD & connective tissue condition relates to the disturbance in substance P levels that can occur when the trigeminal nerve is pathologically stimulated or the temporomandibular joint becomes inflamed (Appelgren et al, 1998; Henry & Walford, 2001; Jennings, 2013).

Salo et al (2007) studied the numerous regulatory neuropeptides that are produced & secreted by neurons, reporting that substance P & calcitonin gene related peptide (CGRP) are two of the most widely distributed & best characterised of all.

Salo, P. et al.  Neuropeptides regulate expression of matrix molecule, growth factor & inflammatory mediator mRNA in explants of normal & healing medial collateral ligament.  Regulatory Peptides, 2007; 142: pp 1-6

The authors were investigating the role that substance P has as a vasodilator, which increases capillary permeability, causes mast cell degranulation & is a potent leukocyte chemotactic agent.  

The study used normal medial collateral ligament (MCL) tissue, which had been subjected to injury.  The results demonstrated that substance P induced significant increases in mRNA levels for several inflammatory mediators in the two-week post-injury specimens.

These results support the theory that both substance P is a powerful influencing factor of the metabolic activity of cells in healing ligaments, especially in the early stages following injury.

In addition, both substance P & CGRP induced decreases in mRNA levels for healing-associated growth factors & matrix molecules, including collagen Types I & III, as well as basic fibroblastic growth factor (bFGF) & vascular endothelial growth factor (VEGF) in the ligament specimens.

Given that both substance P & CGRP were shown to induce significantly lower mRNA levels for these molecules associated with healing in the MCL scar, it could be hypothesised that continued elevation of systemic substance P levels might continue to influence tissue adaptation later in the remodelling stages of ligaments in much the same way that has been seen in tendon tissue. 

The findings of the study by Salo et al, relating to the influence substance P had on injured & remodelling ligament, draws to attention the earlier work that Hecker-Kia et al (1997) had conducted, looking at cartilaginous tissue.

Hecker-Kia et al.  Substance P induces the secretion of gelatinase A from human synovial fibroblasts.  Eur J Clin Chem Clin Biochem, 1997; 35(9): pp 655-660

Hecker-Kia et al investigated the effect that substance P had on the proliferative processes involved in cartilage tissue degeneration in humans & reported that significant rises in gelatinise A, collagenous & MMP3 activity were recorded in response to substance P stimulation.  

Elevated levels of these proteinases were shown to be involved in the proliferative processes leading to cartilage destruction.  For example, gelatinise A is a matrix metalloproteinase, which is able to easily invade cells, potentially enabling it to destroy components of the cell matrix.  

These results reinforced those of Lotz et al (1987) who demonstrated a 5-8 times increase in collagenolytic activity, specific to Type III collagen in the synovitic tissue in rheumatoid patients.

Lotz, M. et al.  Substance P activation of rheumatoid synoviocytes:  neural pathway in pathogenesis of arthritis.  Science, 1987; 235: pp 893-895

Meanwhile, a more recent study by Ramos et al (2007) looking at the effect of inflammatory-induced elevation of substance P levels on the collagen structure in human lung tissue, also reported an up-regulation of another metalloproteinase.  

Whilst increased substance P resulted in an up-regulation of matrix metalloproteinase-1, the authors observed a down-regulation of collagen production.  This implied that substance P had a powerful influence on extracellular matrix metabolism, decreasing collagen biosynthesis & increasing collagen degradation.

Once again, if we consider the physical demands that many football, basketball, soccer & track athletes are subjected too on a regular basis, shouldn’t we be asking why some individuals suffer inflammatory-related joint degeneration & seem to be more at risk of catastrophic ligament damage, whilst others seem to survive relatively unscathed?

As a result, conducting more research into potential links between TMJD, elevated systemic substance P levels & the potential subsequent impact on ligament or joints, would seem a worthwhile use of resources.

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