Category Archives: Neuropathic pain

27Jan/14

Where do we tackle pain?

When someone tells you that they have a painful knee, it makes sense to have a look at the joint to see what has gone wrong. Perhaps an x-ray or a scan would help to determine the state of the cartilage, bone and surrounding soft tissue. An assessment of the range of motion, motor control and the responses to sensory testing reveal any functional limitations and adaptations. Is this enough to truly understand where pain really sits? Is it enough to decide where to intervene? In some cases yes is the answer, but not always!

Important that this kind of evaluation maybe, we must consider the significant pile of literature that points out pain is not an accurate indicator of tissue damage, as so eloquently concluded by Lorimer Moseley. One has only to think about phantom limb pain to realise that there is no need to have an arm, or a leg, or indeed any body part, for there to be pain in that location.

Phantom limb pain is the condition that illustrates the concept that pain is allocated a space. This space could be the knee as in our example above, any other body region or regions, or even outside of the body. A study by Lorimer Moseley also suggested that pain is felt in a space and not within the tissues. Subjects were asked to cross their arms, placing the affected hand into the space usually occupied by the unaffected hand. The effect? Pain relief. This is of course one study, however there was an impact that needs to be further investigated. Assuming that pain is allocated a space, this would explain why, when you position the hand in that of the non-painful side, both the pain and movement quality improve.

This is easily tested in the clinic with both hands and feet. The demonstration is a potent one for the individual as their limb experience can change. Seemingly there is an ease of the tension and guarding as well as the sensitivity. It can be profound, especially when someone has been suffering with a nasty pain such as in complex regional pain syndrome (CRPS) or neuropathic pain. The caveat is that this is not a cure, and it does not work every time, however in those that the effect is apparent, the ability to move more normally promotes healthy tissue and perception by the brain, especially if you are looking at the movement — extra sensory feedback via the visual system.

In summary, as best we know, pain is allocated a space. This can be a space that is occupied by a body region that why we feel pain in the tissues, the place where the pain emerges. The actual location of the pain is determined by the brain as it decides where we need to attend for protection. Recall that pain is a protective device involving a widespread network of neurons within the brain. There is no higher pain centre, but rather a network that monitors the sensory situation and responds as needed. On the basis that the sensory feedback suggests something dangerous is happening, the network will create an output that we experience in the body via a space that is deemed to need protection. Unfortunately, this output can occur without sensory input in some cases of persisting pain as the neuroimmune system becomes very sensitised and responsive to a range of stimuli including those that are not actually dangerous, hence why normal activities can hurt.

On this basis, when considering where to treat pain, we have to consider the space where the brain feels we need protecting. With the emergent property that is pain, the sensation is at the end of a process and it is therefore wise to target the entire biology from top to bottom and bottom to top. This means we need to address the higher centres, for example developing the individual’s understanding of their pain, reducing fears and using strategies for the brain maps of the body concurrent with using techniques within the space, i.e. the body area where the pain is felt.

For more about our comprehensive treatment and training programmes for persisting pain and injury, call us on 07932 689081 to make an appointment. Clinics in London & Surrey.

 

28Sep/13

You’ve had an intervention for pain – what is next?

Many people with persisting and chronic pain elect to have an intervention for pain relief. This can include steroid injections, facet joint injections, nerve root blocks, epidurals, denervations and sympathetic blocks to name but a few. These procedures are usually administered by a pain consultant (a doctor who specialises in pain management), an orthopaedic surgeon, a radiologist or a rheumatologist.

Undoubtedly, the interventions can afford pain relief but of course the results do tend to vary from person to person. Ideally, the procedure forms part of a multidimensional treatment programme that aims to reduce symptoms, increase activity levels and improve quality of life in the patient’s eyes.

So, what happens next?

In some cases nothing and in others patients are advised to reactivate with the help of a physiotherapist. In the former scenario, the expectation is that the procedure will solve the problem, the pain will ease and life returns to normal. Unfortunately there is an error with this thinking as in the vast majority of cases this leaves the patient with a host of unanswered questions: how much should I do? Can I do this or that? Is it safe? etc etc. If the pain persists in any shape or form, this increases the threat value of these questions. They must be answered with practical solutions.

Undoubtedly to follow a comprehensive programme that addresses the physical and cognitive dimensions of pain is desirable. The intensity and length of a programme will vary from person to person, but as a minimum, the patient should know what they can do and how they can do it as a way of moving forward.

Within the programme there are fundamental issues that must be tackled. For example, in many cases of persisting pain, the way in which movement is controlled has changed as has body perception. This has to be retrained and there are specific ways of achieving this goal. We know that these mechanisms play a role in sensitivity and hence need to be targeted.

Concurrent with physical training is the absolute need to create the right mindset and deal with any associated fears of movement. This may include working upon resilience, motivation and coping so that the training outcomes are optimised.

In summary, the understandable use of pain interventions should be part of a multidimensional treatment and training programme that tackles the physical, cognitive and emotional aspects of the pain problem.

12Feb/12

Pain Mechanisms – what underpins our pain?

Understanding pain mechanisms is the key to effective treatment. The mechanisms that have been studied, written about in science journals and discussed with patients include nociceptive pain, inflammatory pain, neuropathic pain and central sensitisation. Elucidating which are playing a role in the patient’s experience allows the doctor to prescribe the right medication and the modern physical therapist to address the issues of pain in a biopsychosocial manner. I will now clarify the latter point.

In taking a detailed history, observing patterns of movement and protection, assessing the state of the nervous system and health of the body systems, understanding behaviours and the beliefs behind them and learning of the influences upon the individual’s pain experience, one can know about the likely pain mechanisms underpinning the experience. From here the treatment strategies can be chosen to target these mechanisms. For example, top-down approaches for central sensitisation focus on the change in the properties of the central nervous system. The interventions themselves are observant of the amplification that occurs in the spinal cord and higher centres and would seek to dampen the responses with input to the brain that is perceived as normal or non-threatening. This could include sensory stimulation or movements outside of the receptive field, education to reduce fear of movement or imagery to name but a few. Inflammatory pain can also be treated with a top-down approach but local tissue based strategies would also be used. Just to note that the separation of the ‘top end’ (brain and spinal cord) from ‘bottom end’ (tissues) is really a false dichotomy as all conscious experiences are from the brain including what we see and what we feel.

Stephen McMahon and David Bennett, both experts in the field of pain science from King’s College London, produced a poster that describes these mechanisms – click here to visit the page in Nature Reviews Neuroscience. This is what they say about it:

Pain is an unpleasant sensation resulting from the intricate interplay between sensory and cognitive mechanisms. Chronic pain, resulting from disease or injury, affects nearly every fifth person in the Western world, constituting an enormous burden for the individual and society. Sensitization of pain signalling systems is a key feature of chronic pain and results in normally non-painful stimuli eliciting pain. Such sensory changes can occur not just at the sites of injury, but in surrounding normal tissues. This and other observations suggest that sensitization occurs within the CNS as well as within nociceptor terminals. Here we consider the consequences of noxious stimulus applied to our unfortunate builder’s hand, from sensory transduction to pain perception. We describe the structural and functional elements present at different levels of the nociceptive system, as well as some of the changes occurring in chronic pain states. Although our poster highlights a flow of information from the periphery to the CNS, it should be noted that higher brain centres exert both inhibitory and facilitatory controls on lower ones. The challenge for the next decade will be to effectively translate this knowledge into the development of novel analgesic agents for better pain relief.

11Feb/12

Manual therapy, pain and the immune system

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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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.

21Oct/11

Using neuroscience to understand and treat pain

I love neuroscience. It makes my job much easier despite being a hugely complex subject. Neuroscience research has cast light over some of the vast workings of our brains and helped to explain how we experience ourselves and the richness of life. An enormous topic, in this blog I am briefly going to outline the way in which I use contemporary neuroscience to understand pain and how we can use this knowledge to treat pain more effectively. This is not about the management of pain, it is the treatment of pain. Management of pain is old news.

Understanding pain is the first step towards changing the painful experience. Knowing how the brain and nervous system operate allows us to create therapies that target the biological mechanisms that underpin pain. Appreciation of the plastic ability of the nervous system from top to bottom–brain to periphery–provides us with the opportunity to ‘re-wire’, and therefore to alter the function of the system and make things feel better. Knowing the role of the other body systems when the brain is defending us, is equally important. The synergy of inputs from the immune system, endocrine system and autonomic nervous system provides the brain with infomration about our internal physiology that it must scrutinse and act upon in the most appropriate way. We call this action the brain’s ‘output’ which is the responses that it co-ordinates to promote health and survival.

Excellent data from contemporary research tells us that understanding pain increases the pain threshold (harder to trigger pain), reduces anxiety in relation to pain and enhances our ability to cope and deal with the pain. We know that movement can also improve after an education session. This is because the perceived threat is reduced by learning and understanding what is going on inside, and knowing what can be done. The vast majority of patients who come to the clinic do not know why their pain has persisted, what pain really is, how it is influenced and what they can do about it themselves. For me this is the start point. Explaining the neuroscience of pain. Facts that we know people can absorb, understand and apply to themselves in such a way that the brain changes and provides a different experience.

It is the brain that gives us our experience of ourselves and the world around us. This includes the sensory and emotional experience of pain. The brain receives information from the body via the peripheral nervous system that suggests there is a threat to the tissues (input). In response, the brain must decide whether this threat is genuine based upon what is happening at the time, the emotional state, past experience, the belief system, gender, genetics, health status, culture and other factors. In the case that the brain perceives a threat, the output will be pain. The Mature Organism Model developed by Louis Gifford describes this beautifully (see below).

Pain is a motivator. It grabs our attention in the area of the body that the brain feels is threatened based upon the danger signals it is receiving from the tissues via the spinal cord. The brain actually ascribes the location of the pain via the map of the body that exist in the sensory cortex. On feeling the pain, we take action. This is the reason for pain. It motivates us to move, seek help or rest. Pain is an incredible device that we have for survival and learning, necessary to navigate life and completely normal. The brain constructs the pain experience and associated symptoms in such a way that we have to take note and do something about it immediately.