Honolulu, Hawai'i, USA
Tuesday 9th October 2012
After enjoying a few days on Maui, I arrived in Honolulu on the island of Oahu on Saturday morning, to meet up with my friend & athletic trainer at the University of Hawai'i, Jayson Goo.  Jay is one of the core group of Kinesio Tape trainers, having taught & lectured on the topic for around 11 years, which is how our paths initially crossed in Edinburgh back in 2007.

Since I arrived in my hotel on Waikiki Beach, Jay has gotten me involved working with the University's women's soccer team.  On Sunday they played a conference game against a team from California, which ended with a 0-1 defeat after nearly the whole of the allowed double over time period had passed before the winning goal was scored.  On Monday morning, the girls were back in training at 6am & after lectures, they were back in the training room for treatment.  It's a tough job playing NCAA soccer!!!

Tonight I fly to San Diego to speak on the DJO Global annual foot & ankle invitational.  I really enjoyed the course last year & am honoured to have been asked back to provide a sports physiotherapy perspective on injury management.  I will post my presentation on the blog once it is finished, however, in the meantime, here are more of my notes from the lectures delivered in Vancouver at the International Scientific Tendinopathy Symposium.

International Scientific Tendinopathy Symposium, Vancouver, 2012


Session 1


THE CHALLENGE OF TENDON PAIN (tennis elbow) - Bill Vicenzino


1. Widespread hyperalgaesia - pressure pain threshold assessed

2. Ipsilateral thermohyperalgaesia & bilateral cold hyperalgaesia in the most severe presentations

3. Nociceptive flexion reflex threshold (Rhudy & France, 2007) response indicates spinal cord hyper excitability in chronic lateral epichondylalgia, implying dorsal horn changes (Lim et al, 2012)

4. Bisset L et al (2006) - MWM & exercise reverse the NFR threshold changes in chronic patients

5. Conditioned pain modulation - test stimulus (pressure pain stimulus) is increased by conditioning heat stimulus in normal subjects - but no change in tennis elbow patients

This means that CPM might be augmented with manual therapy (Skyba et al, 2003 & Paungmali et al, 2003)



Bisset, L. et al (2006).  Mobilisation with movement & exercise, corticosteroid injection, or wait & see for tennis elbow: randomised trial.  BMJ; doi: 10.1136/bmj.38961.584653.AE

Lim, E.C.W. et al (2012).  Evidence of spinal cord hyperexcitability as measured with nociceptive flexion reflex (NFR) threshold in chronic lateral epicondylalgiawith or without a positive neurodynamic test.  J of Pain; 13(7): pp676-684

Paungmali, A. et al (2003) Hypoalgesic & sympathoexcitatory effects of mobilization with movement for lateral epichondylalgia. Phys Ther; 83: pp374-383

Rhudy, J.L. & France, C.R. (2007).  Defining the nociceptive flexion reflex (NFR) threshold in human participants: A comparison of different scoring criteria.  Pain; 128(3): pp244-253

Skyba, D.A. et al (2003).  Joint manipulation reduces hyperalgesia by activation of monoamine receptors but not opioid or GABA receptors in the spinal cord.  Pain; 106(1-2): pp.159-168




Tendinopathy with tendonosis:

What induces tendonosis & pain? Biochemical in origin...micro dialysis studies have shown elevated levels of glutamate (Alfredsson, 1999, 2000, 2005)

Receptors of Substance P & catecholamines are all present on blood vessel (arteries & small vessels) cells (Danielson et al, 2006) & tenocytes (Andersson et al, 2008)


“…biopsies from the proximal part of normal and pain-free patellar tendons (11 men, mean age 33 years) were examined. The specimens were evaluated by using antibodies against the general nerve marker protein gene-product 9.5 (PGP 9.5) and the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and immunohistochemistry. It was observed that the arteries, and to some extent the small vessels, in the loose paratendinous connective tissue were supplied with PGP 9.5- as well as SP- and CGRP-innervations. There was a marked PGP 9.5-like immunoreaction (LI), and to some extent also SP- and CGRP-LI, in the large nerve fascicles in this tissue. In the tendon tissue proper, PGP 9.5-LI was detected in nerve fibers located in the vicinity of some of the blood vessels and in thin nerve fascicles. There was a low degree of SP- and CGRP-innervation in the tendon tissue proper. The observations give a morphologic correlate for the occurrence of nerve-mediated effects in the patellar tendon. Particularly it seems as if there is a marked nerve-mediated regulation of the blood vessels supplying the tendon, at the level where they course in the loose paratendinous connective tissue.”  (Danielson et al, 2006)

Cause & effect - Rabbit model: production of substance P is increased after strain & this elevation precedes the tendonosis tissue changes & is seen also on the contralateral side

In the vitro model - rate of proliferation is increased in response to exogenesis (Andersson, 2011)

Clinical implications - Blocking of receptors proven to be degenerative or nerve irritating?

Alfredson, H. (2005) The chronic painful Achilles & patellar tendon: Research on basic biology & treatment.  Scand J Med Sci Sports; 15: pp252-259

Andersson, G et al (2011) Substance P accelerates hypercellularity & angiogenesis in tendon tissue & enhances paratendinitis in response to Achilles tendon overuse in a tendinopathy model.  BJSM; 45: pp1017-1022

Andersson, G. et al (2011). Tenocyte hypercellularity and vascular proliferation in a rabbit model of tendinopathy: contralateral effects suggest the involvement of central neuronal mechanisms. Br J Sports Med;45: pp399-406 

Andersson, G et al (2008) Presence of substance P & the neurokinin-1 receptor in tenocytes of the human Achilles tendon.  Regulatory Peptides; 150(1-3): pp81-87

Danielson, P. et al (2006).  Distribution of general (PGP 9.5) & sensory (substance P & CGRP) innervations in the human patellar tendon.  Knee Surg Sports Traumatol Arthrosc; 14: pp125-132



Where is the pain coming from?  

Increase in mast cell populations present in tissue associated with regional pain syndromes


Tendinopathy is one such condition where pain is not considered proportionate to tissue changes

Substance P, affects vascularity & nerves


Mast cells are known mediators of inflammatory responses to injury but also regulate cell proliferation & vasodilation in certain tissues by releasing histamine, tryptase, serotonin & cytokines via PARs

Biopsies from Achilles' tendons show that PAR1 receptor cell expression was present in vessels & nerve fibres (stimulates angiogenesis, regulates vascular permeability

PAR 2 was found in tendon cells, cultured cells, vessels & nerve fibres (stimulate fibroblast proliferation)

PAR 3 was found on tenocytes, vessels & nerve fibres 

Activation via PAR 4 in tenocytes, cultured cells, vessels both in the tendon tissue proper as well as ventral to the tendon & found on substance p nerve fibres (have pro inflammatory effects, analgesic) may lead to increased nociception in joints

Clinical Implications – PAR4 may be responsible for tenocyte proliferation & vascular regulation in addition to enhanced pain signalling in tendinopathy through substance P positive afferents



Pain system is ever changing - central sensitisation links pain & touch pathways, triggering pain at much lower thresholds

The aetiology & pain mechanisms of tendinopathy are not completely understood - Mismatch between pain & tendon pathology


Little is known as to whether or to which degree somatosensory changes within the nervous system contribute to pain in tendonopathy

Quantative sensory testing (Rolke, 2006)

Injured athletes had significantly lower mechanical pain & vibration disappearance thresholds

As this was only apparent in some athletes, suggesting success of painful treatments in desensitising the tissue (shock wave), or central acting drugs, whilst genetics might also contribute

The study by van Wilgen et al (2011) concluded that sensitisation may play a prominent role in the pain during & after sports activity in patella tendinopathy patients

Clinical Implications – sensitisation may play a prominent role in the pain experienced during & after sports activity by patellar tendinopathy patients



Rolke, R. et al (2006).  Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS):  Standardized protocol & reference values.  Pain; 123: pp231-243

Van Wilgen, C.P. et al (2011).  Do patients with chronic patellar tendinopathy have an altered somatosensory profile?  - A Quantitative Sensory Testing (QST) study.  Scand J Med Sci Sports; doi: 10.1111/j.1600-0838.2011.01375.x



Tendon mineralisation might occur bilaterally in response to unilateral injury

Mineralisation of tendons can lead to pain, resulting in underuse & a weaker tendon

Low load through underuse can cause an increase in hysteresis & decrease in tendon stiffness

The impact of this mineralisation on these tendon properties is unknown


High load (failure) biomechanical tests were performed in mice

Results showed mineralisation in both the ipsilateral & contralateral tendons

Creep in the non injured leg was significantly greater than creep in the injured leg - unilateral injury was shown to effect biomechanical changes in the uninjured leg & increased creep

Tendons failed close to the insertion


1) Neurological (Decaris et al 1999, Arthritis Rheum)

2) Circulatory

3) Change in loading

Clinical Implications - consider bilateral occurrence on assessment


O’Brien, E.J.O. et al (2012).  Heterotopic mineralization (ossification or calcification) in tendinopathy or following surgical tendon trauma.  Int J Exp Path; 93(5): pp319-331

Mikic, B. et al (2009).  Sex matters in the establishment of murine tendon composition & material properties during growth.  J Orthop Res; 28(5): pp 631-638



Human tendons have the capacity to produce acetylcholine but also express acetylcholine receptors...increased production & receptor expression in tendinosis

Hypercellularity & angiogenesis are key histopathological features in tendonosis tissue

The proliferative effect of acetylcholine was decreased in response to atropine

Hypercellularity might be a part of the healing or adaptive response in the early stage of tendinosis but excessive tenocyte proliferation could be detrimental to tendon structure & function in the chronic stage

The non-neuronal cholinergic system of tendon tissue is therefore a possible target for future modulation of these processes in tendinosis



Whilst the focus has been on tendon pathology in tendinopathy, the potentially widespread systemic effects on the pain, motor & sensory systems are poorly understood.

20 studies included, with concentration on lateral epicondylalgia

5 papers showed a significant decrease in sensory pressure thresholds on the contra lateral side

Heat pain thresholds were overall shown to have decreased on the contralateral side

Reaction time & two-choice reaction time were seen to have significantly decreased in the studies

Grip strength studies were mixed, with one showing increased strength suggesting compensation but others showing a decrease


Clinical Implications: The presence of widespread changes in measures of pain & sensorimotor function in human studies imply that there is abnormal CNS processing


Fernandez De Las Penas, C. et al (2009).  Bilateral widespread mechanical pain sensitivity in carpal tunnel syndrome:  Evidence of central processing in unilateral neuropathy. Brain; 132: pp1472-1479

Genaidy, A.M. et al (2007).  An epidemiological appraisal instrument – a tool for evaluation of epidemiological studies.  Ergonomics; 50(6): pp920-960

Rees, J. et al (2009).  Management of tendinopathy.  AJSM; 37(9): pp1855-1867

Smeulders, M.J.C. et al (2002).  Motor control impairment of the contralateral wrist in patients with unilateral chronic wrist pain.  Am J Phys Med & Rehab; 81(3): pp177-181

Xu, Y. & Murrell, G. (2008).  The basic science of tendinopathy.  CORR; 466(7): pp1528-1538



Evidence of an active process incorporating an inflammatory response

Schubert et al 2005 - macrophages, T & B lymphocytes are seen in chronic tendinopathy 

Tenocytes proliferate in response to cytokines & growth factors that are part of the inflammatory response

Neovessels - indicate active inflammation in a rheumatological context

Prostaglandins - prolonged expression of PG1 & PG2 cause tendon changes (Sullo et al, 2001; Zhang et al, 2010; Khan et al, 2005)...only visible at certain times

Tendon matrix is in total flux

Substance P increases in chronic tendinopathy 



- Corticosteroids but issues remain regarding symptom recurrence & integrity

- NSAIDS, have an effect on nociception but the effect on healing is conflicting (studies show both increase & decrease on stiffness)

- Anti TNF regulates interleukins 1&6, MMP1&3, VEGF, PGE2 

- Nerve growth factor linked with nerve proliferation

The evidence for degeneration alone as the cause of tendinopathy is weak.  There is compelling evidence that inflammation is a key component of chronic tendinopathy.  Newer anti-inflammatory modalities provide alternative potential opportunities in treating chronic tendinopathies


Fredberg, U. & Stengaard-Pedersen, K. (2008).  Chronic tendinopathy tissue pathology, pain mechanisms, & etiology with a special focus on inflammation.  Scand J Med Sci Sports; 18: pp3-15

Khan, M.H. et al (2005).  Repeated exposure of tendon to prostaglandin-E2 leads to localized tendon degeneration.  Clin J Sport Med; 15(1): pp27-33

Sullo, A. et al (2001).  The effects of prolonged peritendinous administration of PGE1 to the rat Achilles tendon: a possible animal model of chronic Achilles tendinopathy. J Ortho Sci; 6(4): pp349-357

Wang, J.H.C. (2006). Mechanobiology of tendon.  J Biomech; 39: pp1563-1582

Zhang, J. & Wang, J.H.C. (2009). Production of PGE2 increases in tendons subjected to repetitive mechanical loading & induces differentiation of tendon stem cells into non-tenocytes. J Orthop Res; 28: pp198-203

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