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 post & 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. In this post, I am going to discuss the possible pathways that are at work in these cases.
The basis of the link between TMJD and 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).
Substance P is the neurotransmitter that is responsible for all pain signals to the brain & systemic levels are significantly influenced by bad jaw alignment. This relationship is due to the proximity of the TMJ to the trigeminal nerve, which has a very dense accumulation of “C fibres”, the afferent nerve fibres that convey input signals from the periphery to the central nervous system & a primary source of substance P.
Some studies report that the number of C fibres in the trigeminal nerve is around 100 times greater than in other nerves. Furthermore, given that C fibres are slow to recover, once the cause of trigeminal stimulation is resolved, it may still take several months for abnormal sensory function to be restored, neuropathic pain to resolve & levels of substance P to return to baseline levels.
Appelgren, A. et al. Substance P-associated increase of intra-articular temperature & pain threshold in the arthritic TMJ. J Orofac Pain, 1988; 12(2): pp 101-107
Jennings, D. Cancer, Substance P & your bite. www.TMJCalifornia.com
The next question to ask, concerns what happens to collagenous structures, such as tendons, when systemic levels of substance P are elevated.
Back in 2012, just after the Olympics & the professional track season were finished, I attended the International Scientific Tendinopathy Symposium in Vancouver, at which Jonathon Rees & Gloria Fong presented some of their work on tendinopathy. It was here that I learnt more about the influence of substance P in tendons, as Rees, Fong & others discussed the research pertinent to this pathway.
My review of their sessions can be seen in my blog post from that week, whilst the consensus paper that I co-authored was taken from that meeting;
Oliver Finlay Blog, October 9, 2012; http://www.oliverfinlay.com/blog.asp?id=OJF-BC10175
Rees et al (2014) reviewed a substantial chunk of studies related to tendinopathy & discussed the role of substance P as an inflammatory mediator.
Rees, J.D. et al. Tendons - time to revisit inflammation. Br J Sports Med, 2014; 48: pp 1553-1557
They pointed to the evidence demonstrating that several biochemical mediators have been shown to influence the progression of chronic tendinopathy & substance P was included in this group (Gotoh et al, 1998; Garrett et al, 1992).
Along with calcitonin gene related peptide (CGRP), substance P & the other biochemical mediators are significantly expressed in chronic tendinopathy, with substance P exerting a proliferative effect on tenocytes.
This should ring alarm bells for those of you that are aware of the effects of increased activity of tenocytes, hyper-cellularity & vascular proliferation in tendon tissue.
For those of you that need a quick revision, it is worth taking the time to read Cook & Purdam’s seminal paper on the continuum of tendon pathology. This should give you a brief overview of how tendon pathology develops from both a clinical & physiological perspective.
In addition to causing tenocyte proliferation, substance P has also been shown to cause tenocytes to adopt a myofibroblast-like phenotype (that means that the tendon cell demonstrates an increased smooth muscle actin expression, which leads to increased contractile activity).
So whereas in normal tendons, the load-bearing collagen fibres are orientated in a regulated, organised manner, in injured tendons, the arrangement is seen to be more disorganised & populated by the myofibroblastic cells with increased smooth muscle actin content.
Fong et al (2013) investigated the influence of substance P on the organisation of collagen & the mRNA levels for the specific type of collagen being produced by the tenocytes. They found that substance P actually increased the rate of collagen remodelling in comparison to controls.
In showing that Type I collagen lattices were remodelled at a greater rate & to a greater extent when treated with substance P, Fong et al indicated that there are biologically relevant effects of substance P in human tendons, which may influence recovery from injury or the development of overuse pathologies such as tendinosis.
This contribution to the development of overuse pathology might be explained by the fact that whilst substance P stimulated an increase in collagen production, the ratio of Type III collagen mRNA:Type I collagen mRNA increased. The thinking is that increased Type III collagen production at the expense of Type I collagen contributes to the formation of smaller collagen fibres that characterise tendonopathic tendons.
Therefore, whilst Fong et al were able to demonstrate that substance P promoted the early tissue proliferation that is essential in the repair of normal tendons in response to acute bouts of heavy loading, their results also suggested that the sustained up-regulation of substance P, seen in tendinosis, might have a negative impact on healing, leading instead to prolonged or excessive collagen remodelling activity.
This may be related to elevated expression of ACTA2 & MMP3 genes, which were observed in the presence of substance P up-regulation & are associated with tendinosis.
These intra-tendinous changes related to elevated substance P levels have been shown to be exacerbated in combination with loading.
Backman et al (2011) showed that in a rabbit model, subjecting the tendon to overload in a substance P-elevated state further increased substance P levels & led to acceleration of the hypercellularity & angiogenesis that was occurring in the pathway of degeneration.
If this were shown to be true in human tendons, this could have significant impact on an athlete’s response to heavy loading sessions if their systemic substance P levels were already elevated, for example in response to TMJD.
Think of the amount of impact-related stretch-shortening the tendons of an basketball player are subjected to, or a football player, or a sprinter & then ask yourself why some individuals do not suffer from overuse injuries, whilst others suffer repeatedly. Could an untreated TMJD be an influencing factor?
To look at the substance P effect from the opposite angle, the study by Andersson et al (2011) concluded that inhibiting substance P could be beneficial in not only reducing pain but also in reducing the ongoing tendon degradation.
Tendon tissue is not the only collagenous tissue that we must consider, however. In my next post, I will turn the spotlight on the research that has investigated the potential impact of elevated substance P levels on the healing & remodelling of both ligament & cartilaginous structures?
