Category Archives: Joint pain

30Sep/12
Why do my knees hurt? Running injuries

Why does my knee hurt when I run?

The success of the London 2012 Olympics has had a huge impact upon society including the greater participation in sporting activities. This is a truly vital legacy and we must seek to pervade this healthy mindset to all corners of the country and across all the age ranges to optimise the benefits.

Those seeking immediate gratification will have pulled out the old trainers, dusted off the bike in the shed or grabbed the shorts (or briefs) and visited the local pool – see Get Active London. This is indeed a welcome shift towards more active lifestyles at a time when we have increasing understanding of the benefits of regular exercise for both body and brain.

Turning our attention to a consequence of either taking up running for the first time or re-starting having had a break, inspired by the mighty achievements of our athletes, there can be a few aches and pains in the knees. Sometimes the onset will be quick and at other times gradual. I will look briefly at why this can happen, remembering that when you increase your level of exercising it is usually quite normal for there to be some pain afterward. If you are unsure it is advisable that you seek the opinion of your local health professional as soon as possible so that the correct treatment and management is started.

Training methods

A sudden change in the demands upon our joints, particularly the knees in running due to the impact, can trigger local sensitivity in the joint and surrounding tissues. We should think carefully about the baseline, or start point from where the programme can be progressed. Too much too soon will hurt and especially if there is not adequate time between exercising bouts for a good level of recovery in the early stages. It may not be the first time out but the second or third that the pain begins.

The shoes that are used are vital. You do not have to spend a small fortune on the latest running kit but it is sensible to have a good trainer that is suitable for your foot type and provides the right kind of support. If you have pulled out an old, smelly pair of runners from under the stairs, you may have problems. Make a visit to a good quality running shop, for example Run & Become.

Where you decide to go running will determine the loading upon the joints. Start easily and gradually build up the time and speed, thinking about where you are training. Up and down hills and uneven grouns will pose more of a challenge of course.

Old injuries

If you have had a problem with your knees before, re-starting running could re-ignite the pain. It is not totally out of the question to take up running again, but you should ensure that the motor control, movement and proprioception is adequate and then gradually build the intensity. It will be best to seek advice in this case as there maybe some essential rehabilitation training that is required before starting the running programme.

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There will be many people enthusiastically exercising as a result of the Olympics and this is to be commended. It is important to really consider how to start training, the baseline and progressions and using the right equipment.

If you have any questions please contact us here or call 07518 445493

24Sep/12
Joint hypermobility syndrome | JHS | Treatment and training for hypermobility

Joint Hypermobility Syndrome (JHS) Part 2: What can we do?

Joint hypermobility syndrome (JHS) is commonly seen in my clinics, either as a feature observed or as a problem in itself – see previous blog. Commonly people desecribe pain, poor spatial awareness (so-called clumsiness), flat-footedness, problems with walking and controlling movement. What can we do about these problems? Firstly, understanding the neuroscience of movement and pain really helps the individual to engage in the training process to craft change and improve pain and performance. Applying what we know from contemporary neuroscience allows us to create individual treatment programmes that tackle the problems at source.

 Spatial awareness and motor control

Traditionally the training to improve spatial awareness and motor control in joint hypermobility syndrome (JHS) involves proprioceptive tasks (balancing in a variety of formats). Undoubtedly this is a vital part of the programme. However, whether this shouild be the start point or a stage to be progressed to depends upon the assessment findings. Clearly there are a number of people who are hypermobile who can actually balance extremely well – dancers and gymnasts of course. However, they are often subject to many aches and pains put down to injury and repetive straining of the tissues beyind the normal range. This can be true. Just returning to a piece of research that found incongruence to cause pain and altered sensation, we know that there are other forces at play, those of the brain. How can we detect what is going on?

In recent times there has been an increase in studies looking at the adaptations that occur in the brain and how these manifest. Certainly we know about changes in two point discrimination that relate to plastic adaptations in the nervous system and in the ability to recognise left and right images of different body regions. Both of these offer assessment that moves beyond the tissues and into the underpinning mechanisms behind altered movement, sense of self and pain – all of which we have identified as features of hypermobility.

Training: I would start the individual upon tactile discrimination training, recalling that normal sensory information is sent to the brain to maintain and integrated view of the body that is vital for the control of movement. If left/right recognition is either slow or inaccurate, or both, the Recognise training will also be commenced, targeting the early mechanisms of movement (the planning phase – an actual movement can only be as good as the plan). From here we progress to specific motor control and proprioceptive exercises with an emphasis upon quality of movement and feedback.

Strength

Strength is very important and often found lacking in hypermobility. On a day-to-day basis it may not be too obvious that there is a strength deficit, however on testing the reality is different. Interestingly, a study looked at the effects of a home based strengthening programme and found that as well as strength gains, proprioception improved as did pain. The nerve endings in muscles and tendons send a great deal of information to the brain about movement and tension that could explain the improved sense. The increase in capillaries within the muscles as a result of exercising will improve the blood and oxygen supply thereby nourishing the tissues.

Training: From a baseline the resistence is gradually increased using body weight and hand-held weights, targeting both individual muscles and groups of muscles that work functionally together.

Pain

Reducing the pain and sensitivity is always a goal of the treatment programme. This is both directly with therapies targeting the pain mechanism(s) and by training the brain.

We know that from modern neuroscience research that pain is a brain experience 100% of the time and that the feeling of pain is allocated a location in the body, therefore targeting the brain as well as the health of the tissues is vital. This includes developing a good understanding of your pain and the influences upon it. Lifestyle (e.g./ diet & exercise, work habits), stress, fatigue, mood and emotional state all play a significant role in the sensitivity of the nervous system. We address all of these factors to provide a comprehensive treatment programme that is designed for you to reach your goals.

Summary

To deal with the problems that can arise in association with hypermobility takes a rounded approach with a solid neuroscience backing that recognises the individual. This is in fact the same approach for any persisting or more complex pain case. We must look at the problems and concerns and subsequently deliver treatment and therapy that is tailored in order to reduce the sensitivity, increase confidence, promote healthy habits and restore desirable activity levels.

For further information or to book an appointment please contact us: 07518 445493

 

11Feb/12

Manual therapy, pain and the immune system

Pain relief

As a physiotherapist I frequently use my hands to treat the joints and tissues. It comes with the territory, everyone expects hands-on therapy and it does helps to reduce tension and pain. Most likely, the pain relief from joint mobilisation is due to descending mechanisms that include those that are powered by serotonin and noradrenaline (see here). This is very useful to know as it tells us about the effects of passively moving joints and importantly permits wise selection of techniques to target the pain mechanisms. Building on the knowledge base, two very recent studies have identified some extremely interesting results.

Firstly, Martins et al. (2011) found that ankle joint mobilisation reduced pain in a neuropathic pain model in rats along with seeing the regeneration of nerve tissue and inhibition of glial cell activation (a blog will be coming soon that discusses the immune system in pain states) in the dorsal horn of the spinal cord. Secondly, Crane et al. (2012) looked at how massage helps reduce the pain of exercise-induced muscle damage in young males. Taking muscle biopsies they found that massaged subjects demonstrated attenuation of proinflammatory cytokines, key players in sensitisation. It was also noted that massage had no effect upon metabolites such as lactate – see below.

More research into the mechanisms that underpin the effects of hands-on therapy is needed despite the advancements in our understanding. The ability to focus treatment upon this understanding can only develop our effectiveness in treating pain. I am very optimistic about the movement forwards in pain and basic science, and how this can be applied  in our thinking with individual patients. The language is changing with the words ‘treatment’ being used rather than ‘management’, the latter of which can imply that one has reached their limit of improvement. This is exciting and more importantly, realistic when one considers therapies such as the graded motor imagery. We do not have treatments that work for all pains but we do have brains and body systems that are flexible, dynamic and can change if given the opportunity, the right stimulation within the right context on the background of good understanding. It is our duty to keep this rolling onwards and thinking hard about how to best use the findings such as those highlighted in this blog.

Pain. 2011 Nov;152(11):2653-61. Epub 2011 Sep 8.

Ankle joint mobilization reduces axonotmesis-induced neuropathic pain and glial activation in the spinal cord and enhances nerve regeneration in rats.

Martins DF, Mazzardo-Martins L, Gadotti VM, Nascimento FP, Lima DA, Speckhann B, Favretto GA, Bobinski F, Cargnin-Ferreira E, Bressan E, Dutra RC, Calixto JB, Santos AR.

Source

Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, Brazil.

Abstract

An important issue in physical rehabilitation is how to protect from or to reduce the effects of peripheral nerve injury. In the present study, we examined whether ankle joint mobilization (AJM) would reduce neuropathic pain and enhance motor functional recovery after nerve injury. In the axonotmesis model, AJM during 15 sessions every other day was conducted in rats. Mechanical and thermal hyperalgesia and motor performance deficit were measured for 5 weeks. After 5 weeks, we performed morphological analysis and quantified the immunoreactivity for CD11b/c and glial fibrillary acidic protein (GFAP), markers of glial activation, in the lumbar spinal cord. Mechanical and thermal hyperalgesia and motor performance deficit were found in the Crush+Anesthesia (Anes) group (P<0.001), which was significantly decreased after AJM (P<0.001). In the morphological analysis, the Crush+Anes group presented reduced myelin sheath thickness (P<0.05), but the AJM group presented enhanced myelin sheath thickness (P<0.05). Peripheral nerve injury increased the immunoreactivity for CD11b/c and GFAP in the spinal cord (P<0.05), and AJM markedly reduced CD11b/c and GFAP immunoreactivity (P<0.01). These results show that AJM in rats produces an antihyperalgesic effect and peripheral nerve regeneration through the inhibition of glial activation in the dorsal horn of the spinal cord. These findings suggest new approaches for physical rehabilitation to protect from or reduce the effects of nerve injury.

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Sci Transl Med. 2012 Feb 1;4(119):119ra13.

Massage therapy attenuates inflammatory signaling after exercise-induced muscle damage.

Crane JD, Ogborn DI, Cupido C, Melov S, Hubbard A, Bourgeois JM, Tarnopolsky MA.

Source

Department of Kinesiology, McMaster University, Hamilton, Ontario L8S 4L8, Canada.

Abstract

Massage therapy is commonly used during physical rehabilitation of skeletal muscle to ameliorate pain and promote recovery from injury. Although there is evidence that massage may relieve pain in injured muscle, how massage affects cellular function remains unknown. To assess the effects of massage, we administered either massage therapy or no treatment to separate quadriceps of 11 young male participants after exercise-induced muscle damage. Muscle biopsies were acquired from the quadriceps (vastus lateralis) at baseline, immediately after 10 min of massage treatment, and after a 2.5-hour period of recovery. We found that massage activated the mechanotransduction signaling pathways focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1/2 (ERK1/2), potentiated mitochondrial biogenesis signaling [nuclear peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)], and mitigated the rise in nuclear factor κB (NFκB) (p65) nuclear accumulation caused by exercise-induced muscle trauma. Moreover, despite having no effect on muscle metabolites (glycogen, lactate), massage attenuated the production of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and reduced heat shock protein 27 (HSP27) phosphorylation, thereby mitigating cellular stress resulting from myofiber injury. In summary, when administered to skeletal muscle that has been acutely damaged through exercise, massage therapy appears to be clinically beneficial by reducing inflammation and promoting mitochondrial biogenesis.

21Jan/12

Central sensitisation is more common than you may think

Clifford Woolf recently said this about central sensitisation:

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.

And Latremolier

Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification. Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations. PERSPECTIVE: In this article, we review the major triggers that initiate and maintain central sensitization in healthy individuals in response to nociceptor input and in patients with inflammatory and neuropathic pain, emphasizing the fundamental contribution and multiple mechanisms of synaptic plasticity caused by changes in the density, nature, and properties of ionotropic and metabotropic glutamate receptors.

In essence we are talking about changes within the central nervous system that underpin the widespread, unpredictable and varied nature of persisting pain.

When I am listening to a patient, observing their movements and performing a ‘multi-system’ examination, I am in part looking for the pain mechanisms at play, including central sensitisation. Several of my questions are: ‘what is going on here to create this experience for the person in front of me?’, ‘why are the nervous and other systems responding in such a way?’ and ‘what is influencing the behaviour of those systems?’. I really need to know what it is that is prolonging this protection and is it really worthwhile for the individual.

Suspecting that there is a component of central sensitisation at play in many cases of chronic pain that I see, it is pleasing to see a group looking at this closely and finding evidence to support this thinking:

J Bone Joint Surg Br. 2011 Apr;93(4):498-502.

Evidence that central sensitisation is present in patients with shoulder impingement syndrome and influences the outcome after surgery.

Gwilym SE, Oag HC, Tracey I, Carr AJ.

Source

Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford OX3 7LD, UK. [email protected]

Abstract

Impingement syndrome in the shoulder has generally been considered to be a clinical condition of mechanical origin. However, anomalies exist between the pathology in the subacromial space and the degree of pain experienced. These may be explained by variations in the processing of nociceptive inputs between different patients. We investigated the evidence for augmented pain transmission (central sensitisation) in patients with impingement, and the relationship between pre-operative central sensitisation and the outcomes following arthroscopic subacromial decompression. We recruited 17 patients with unilateral impingement of the shoulder and 17 age- and gender-matched controls, all of whom underwent quantitative sensory testing to detect thresholds for mechanical stimuli, distinctions between sharp and blunt punctate stimuli, and heat pain. Additionally Oxford shoulder scores to assess pain and function, and PainDETECT questionnaires to identify ‘neuropathic’ and referred symptoms were completed. Patients completed these questionnaires pre-operatively and three months post-operatively. A significant proportion of patients awaiting subacromial decompression had referred pain radiating down the arm and had significant hyperalgesia to punctate stimulus of the skin compared with controls (unpaired t-test, p < 0.0001). These are felt to represent peripheral manifestations of augmented central pain processing (central sensitisation). The presence of either hyperalgesia or referred pain pre-operatively resulted in a significantly worse outcome from decompression three months after surgery (unpaired t-test, p = 0.04 and p = 0.005, respectively). These observations confirm the presence of central sensitisation in a proportion of patients with shoulder pain associated with impingement. Also, if patients had relatively high levels of central sensitisation pre-operatively, as indicated by higher levels of punctate hyperalgesia and/or referred pain, the outcome three months after subacromial decompression was significantly worse.

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Treat the brain, treat the pain

Arthritis Rheum. 2009 Sep 15;61(9):1226-34.

Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients.

Gwilym SE, Keltner JR, Warnaby CE, Carr AJ, Chizh B, Chessell I, Tracey I.

Source

University of Oxford, Oxford, UK. [email protected]

Abstract

OBJECTIVE:

The groin pain experienced by patients with hip osteoarthritis (OA) is often accompanied by areas of referred pain and changes in skin sensitivity. We aimed to identify the supraspinal influences that underlie these clinical manifestations that we consider indicative of possible central sensitization.

METHODS:

Twenty patients with hip OA awaiting joint replacement and displaying signs of referred pain were recruited into the study, together with age-matched controls. All subjects completed pain psychology questionnaires and underwent quantitative sensory testing (QST) in their area of referred pain. Twelve of 20 patients and their age- and sex-matched controls underwent functional magnetic resonance imaging (MRI) while the areas of referred pain were stimulated using cold stimuli (12 degrees C) and punctate stimuli (256 mN). The remaining 8 of 20 patients underwent punctate stimulation only.

RESULTS:

Patients were found to have significantly lower threshold perception to punctate stimuli and were hyperalgesic to the noxious punctate stimulus in their areas of referred pain. Functional brain imaging illustrated significantly greater activation in the brainstem of OA patients in response to punctate stimulation of their referred pain areas compared with healthy controls, and the magnitude of this activation positively correlated with the extent of neuropathic-like elements to the patient’s pain, as indicated by the PainDETECT score.

DISCUSSION:

Using psychophysical (QST) and brain imaging methods (functional MRI), we have identified increased activity with the periaqueductal grey matter associated with stimulation of the skin in referred pain areas of patients with hip OA. This offers a central target for analgesia aimed at improving the treatment of this largely peripheral disease.

18Jan/12

Contemporary understanding of factors in joint pain

Recent research has identified biological reasons for joint pain in arthritis:

  • Interleukin-6, a pro-inflammatory cytokine released both locally at the joint and in the spinal cord, consequently plays a role in the widespread nature of the pain via its role in central sensitisation.
  • Sprouting of sensory and sympathetic fibres at the joint may well have a role in sensitisation
  • Angiogenesis, the growth of new blood vessels, at the joint, perhaps having a role in inflammation

Some of this may sound familiar. IL-6 is known to play a role in the spinal cord following nerve injury, sprouting of the sympathetic fibres at the DRG and in tendinopathy, and angiogenesis also seen in tendinopathy. All are clearly responses by the body and are involved in pain–remembering that pain is a brain experience 100% of the time of course.

Spinal interleukin-6 is an amplifier of arthritic pain (Vazquez et al. 2011)

Objective.

Significant joint pain is usually widespread beyond the afflicted joint which results from the sensitization of nociceptive neurons in the central nervous system (central sensitization). In the present study we explored (a) whether the proinflammatory cytokine interleukin-6 (IL-6) in the joint induces central sensitization, (b) whether joint inflammation causes IL-6 release in the spinal cord, and (c) whether spinal IL-6 contributes to central sensitization.

Methods.

In anesthetized rats electrophysiological recordings were made from spinal cord neurons with sensory input from the knee joint. Neuronal responses to mechanical stimulation of the knee and the leg were monitored. IL-6 and its soluble receptor sIL-6R were applied to the knee joint or the spinal cord. Spinal release of IL-6 was measured by ELISA. Sgp130 which neutralizes IL-6/sIL-6R was spinally applied during development of joint inflammation or during established inflammation.

Results.

A single injection of IL-6/sIL-6R into the knee joint as well as spinal application of IL-6/sIL-6R significantly increased the responses of spinal neurons to mechanical stimulation of the knee and ankle joint, i.e. induced central sensitization. Spinally applied sgp130 attenuated this IL-6 effect. Development of knee inflammation caused spinal release of IL-6. Spinal application of spg130 attenuated the development of inflammation-evoked central sensitization but did not reverse it.

Conclusions.

Not only IL-6 in the joint is involved in the generation of joint pain but also IL-6 which is released in the spinal cord. Spinal IL-6 contributes to central sensitization and thus promotes the widespread hyperalgesia in the course of joint disease.

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Neuroplasticity of sensory and sympathetic nerve fibers in the painful arthritic joint (Ghilardi et al. 2011)

Objective.

Many forms of arthritis are accompanied by significant chronic joint pain. Here we studied whether there is significant sprouting of sensory and sympathetic nerve fibers in the painful arthritic knee joint and whether nerve growth factor (NGF) drives this pathological reorganization.

Methods.

A painful arthritic knee joint was produced by injection of complete Freund’s adjuvant (CFA) into the knee joint of young adult mice. CFA-injected mice were then treated systemically with vehicle or anti-NGF antibody. Pain behaviors were assessed and at 28 days following the initial CFA injection, the knee joints were processed for immunohistochemistry using antibodies raised against calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kDa (NF200; sensory nerve fibers), growth associated protein-43 (GAP43; sprouted nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), CD31 (endothelial cells) or CD68 (monocytes/macrophages).

Results.

In CFA-injected mice, but not vehicle-injected mice, there was a significant increase in the density of CD68+ macrophages, CD31+ blood vessels, CGRP+, NF200+, GAP43+, and TH+ nerve fibers in the synovium as well as joint pain-related behaviors. Administration of anti-NGF reduced these pain-related behaviors and the ectopic sprouting of nerve fibers, but had no significant effect on the increase in density of CD31+ blood vessels or CD68+ macrophages.

Conclusions.

Ectopic sprouting of sensory and sympathetic nerve fibers occurs in the painful arthritic joint and may be involved in the generation and maintenance of arthritic pain.

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Contributions of angiogenesis to inflammation, joint damage, and pain in a rat model of osteoarthritis (Ashraf et al. 2011)

Objective

To determine the contributions of angiogenesis to inflammation, joint damage, and pain behavior in a rat meniscal transection model of osteoarthritis (OA).

Methods

OA was induced in male Lewis rats (n = 8 per group) by meniscal transection. Animals were orally dosed with dexamethasone (0.1 mg/kg/day), indomethacin (2 mg/kg/day), or the specific angiogenesis inhibitor PPI-2458 (5 mg/kg every other day). Controls consisted of naive and vehicle-treated rats. Synovial inflammation was measured as the macrophage fractional area (expressed as the percentage), thickness of the synovial lining, and joint swelling. Synovial angiogenesis was measured using the endothelial cell proliferation index and vascular density. Channels positive for vessels at the osteochondral junction were assessed (osteochondral angiogenesis). Medial tibial plateaus were assessed for chondropathy, osteophytosis, and channels crossing the osteochondral junction. Pain behavior was measured as weight-bearing asymmetry.

Results

Dexamethasone and indomethacin each reduced pain behavior, synovial inflammation, and synovial angiogenesis 35 days after meniscal transection. Dexamethasone reduced, but indomethacin had no significant effect on, the total joint damage score. PPI-2458 treatment reduced synovial and osteochondral angiogenesis, synovial inflammation, joint damage, and pain behavior.

Conclusion

Our findings indicate that synovial inflammation and joint damage are closely associated with pain behavior in the meniscal transection model of OA. Inhibition of angiogenesis may reduce pain behavior both by reducing synovitis and by preventing structural change. Targeting angiogenesis could therefore prove useful in reducing pain and structural damage in OA.