CRPS Bugle | March 2014

bugle-450-pic-rexfeatures-271436732Welcome to the March CRPS Bugle, an update on the latest research into complex regional pain syndrome, also known as reflex sympathetic dystrophy (RSD).

Visit our clinic site here for information about our specialist CRPS Clinics.


J Foot Ankle Surg. 2014 Mar 5. pii: S1067-2516(14)00007-6. doi: 10.1053/j.jfas.2014.01.006.

Incidence of Complex Regional Pain Syndrome after Foot and Ankle Surgery.

Rewhorn MJ1, Leung AH2, Gillespie A3, Moir JS3, Miller R4.

Complex regional pain syndrome (CRPS) is an uncommon complication of orthopedic surgery, and few investigators have considered the incidence in foot and ankle surgery. In the present retrospective cohort study of 390 patients who had undergone elective foot and/or ankle surgery in our department from January to December 2009, the incidence of postoperative CRPS was calculated and explanatory variables were analyzed. A total of 17 patients (4.36%) were identified as meeting the International Association for the Study of Pain criteria for the diagnosis of CRPS. Of the 17 patients with CRPS, the mean age was 47.2 ± 9.7 years, and 14 (82.35%) were female. All the operations were elective, and 9 (52.94%) involved the forefoot, 3 (17.65%) the hindfoot, 3 (17.65%) the ankle, and 2 (11.76%) the midfoot. Twelve patients (70.59%) had new-onset CRPS after a primary procedure, and 5 (29.41%) had developed CRPS after multiple surgeries. Three patients (17.65%) had documented nerve damage intraoperatively and thus developed new-onset CRPS type 2. Blood test results were available for 14 patients (82.35%) at a minimum of 3 months postoperatively, and none had elevated inflammatory markers. Five of the patients (29.41%) were smokers, and 8 (47.06%) had had a pre-existing diagnosis of anxiety and/or depression. From our findings, we recommend that middle-age females and those with a history of anxiety or depression, who will undergo elective foot surgery, should be counseled regarding the risk of developing CRPS during the consent process. We recommend similar studies be undertaken in other orthopedic units, and we currently are collecting data from other orthopedic departments within Scotland


Rehabil Psychol. 2014 Mar 10.

Thought Intrusion Among Adults Living With Complex Regional Pain Syndrome.

Lohnberg JA, Altmaier EM.


Purpose: This study investigated the presence and influence of intrusive thoughts among adults previously diagnosed with complex regional pain syndrome. Method: The present study used an Internet-based survey completed by a sample (N = 326) from two national organizations. Results: After controlling for age, gender, and pain level, intrusive thoughts were significantly related to disability and health-related quality of life. Conclusions/Implications: Intrusive thoughts about the inciting event that caused CRPS uniquely influenced pain and quality of life, suggesting a potential mechanism to target for intervention. Understanding factors that relate to maintenance of CRPS and its resulting disability will help in the development of treatments to improve quality of life.


Brain. 2013 Jul;136(Pt 7):2038-49. doi: 10.1093/brain/awt150. Epub 2013 Jun 13.

Secondary and primary dystonia: pathophysiological differences.

Kojovic M1, Pareés I, Kassavetis P, Palomar FJ, Mir P, Teo JT, Cordivari C, Rothwell JC, Bhatia KP, Edwards MJ.

Primary dystonia is thought to be a disorder of the basal ganglia because the symptoms resemble those of patients who have anatomical lesions in the same regions of the brain (secondary dystonia). However, these two groups of patients respond differently to therapy suggesting differences in pathophysiological mechanisms. Pathophysiological deficits in primary dystonia are well characterized and include reduced inhibition at many levels of the motor system and increased plasticity, while emerging evidence suggests additional cerebellar deficits. We compared electrophysiological features of primary and secondary dystonia, using transcranial magnetic stimulation of motor cortex and eye blink classical conditioning paradigm, to test whether dystonia symptoms share the same underlying mechanism. Eleven patients with hemidystonia caused by basal ganglia or thalamic lesions were tested over both hemispheres, corresponding to affected and non-affected side and compared with 10 patients with primary segmental dystonia with arm involvement and 10 healthy participants of similar age. We measured resting motor threshold, active motor threshold, input/output curve, short interval intracortical inhibition and cortical silent period. Plasticity was probed using an excitatory paired associative stimulation protocol. In secondary dystonia cerebellar-dependent conditioning was measured using delayed eye blink classical conditioning paradigm and results were compared with the data of patients with primary dystonia obtained previously. We found no difference in motor thresholds, input/output curves or cortical silent period between patients with secondary and primary dystonia or healthy controls. In secondary dystonia short interval intracortical inhibition was reduced on the affected side, whereas it was normal on the non-affected side. Patients with secondary dystonia had a normal response to the plasticity protocol on both the affected and non-affected side and normal eye blink classical conditioning that was not different from healthy participants. In contrast, patients with primary dystonia showed increased cortical plasticity and reduced eye blink classical conditioning. Normal motor cortex plasticity in secondary dystonia demonstrates that abnormally enhanced cortical plasticity is not required for clinical expression of dystonia, and normal eye blink conditioning suggests an absence of functional cerebellar involvement in this form of dystonia. Reduced short interval intracortical inhibition on the side of the lesion may result from abnormal basal ganglia output or may be a consequence of maintaining an abnormal dystonic posture. Dystonia appears to be a motor symptom that can reflect different pathophysiological states triggered by a variety of insults.


Int J Rheum Dis. 2014 Feb;17(2):156-8. doi: 10.1111/1756-185X.12140. Epub 2013 Jun 24.

Antioxidant profile in patients with complex regional pain syndrome type I.

Baykal T1, Seferoglu B, Karsan O, Kiziltunc A, Senel K.

Complex regional pain syndrome (CRPS) type I is one of the most important problems with regard to physical medicine and rehabilitation. CRPS may cause not only higher therapeutic costs but also greater work time loss. The mechanism and pathogenesis of CRPS still remains unknown. Some findings indicating oxidative stress have been reported. This study was carried out to determine the role of oxidative stress in patients with CRPS.
Twenty patients (13 women and seven men) with CRPS and 20 age- and sex-matched healthy controls were enrolled in this study. Complex regional pain syndrome was diagnosed according to the modified International Association for the Study of Pain (IASP) criteria. We evaluated demographic, clinical and laboratory characteristics of the patients. Antioxidant enzymatic activities consisting of serum superoxide dismutase (SOD), glutathion peroxidase (GPX) and glutathione S-transferase (GST) activities were measured using appropriate methods and compared with healthy controls.
The mean age of the patients was 39.5 years and the mean duration of symptoms was 5.5 months. Complex regional pain syndrome devoleped after a traumatic event in 90% of patients. In 10% of patients there were no traumatic events. SOD, GPX and GST levels were significantly higher in patients with CRPS than healthy controls (P = 0.012, P = 0.036 and P = 0.016, respectively).
Our findings suggest a possible role of oxidative stress in the pathogenesis of CRPS


J Pain. 2014 Feb 11. pii: S1526-5900(14)00565-3. doi: 10.1016/j.jpain.2014.01.500.

The Outcome of Complex Regional Pain Syndrome Type 1: A Systematic Review

Bean DJ1, Johnson MH2, Kydd RR3.

The purpose of this systematic review was to examine the outcome of complex regional pain syndrome (CRPS) type-1. We searched Medline, Embase and Psychinfo for relevant studies, and included 18 studies, with 3991 participants, in this review. The following data were extracted: study details, measurement tools used, and rates or severity scores for the symptoms/signs of CRPS at baseline and follow-up, or in groups of patients with different disease durations. A quality assessment revealed significant limitations in the literature, with many studies utilising different diagnostic criteria. The 3 prospective studies demonstrated that for many patients, symptoms improve markedly within 6-13 months of onset. The 12 retrospective studies had highly heterogeneous findings, documenting lasting impairments in many patients. The 3 cross-sectional studies showed that rates of pain and sensory symptoms were highest amongst those with the longest duration of CRPS. Additionally, most studies showed that motor symptoms (stiffness and weakness) were the most likely to persist whilst sudomotor and vasomotor symptoms were the most likely to improve. Overall, this suggests that some CRPS patients make a good early recovery whilst others develop lasting pain and disability. As yet little is known about the prognostic factors that might differentiate between these groups.
We found evidence that many CRPS patients recover within 6-13 months, but a significant number experience some lasting symptoms, and some experience chronic pain and disability. The quality of the evidence was poor. Future research should examine the factors associated with recovery and identify those at risk of poor outcomes


Eur J Neurosci. 2014 Feb;39(3):508-19. doi: 10.1111/ejn.12462

The neurobiology of skeletal pain.

Mantyh PW.

Disorders of the skeleton are one of the most common causes of chronic pain and long-term physical disability in the world. Chronic skeletal pain is caused by a remarkably diverse group of conditions including trauma-induced fracture, osteoarthritis, osteoporosis, low back pain, orthopedic procedures, celiac disease, sickle cell disease and bone cancer. While these disorders are diverse, what they share in common is that when chronic skeletal pain occurs in these disorders, there are currently few therapies that can fully control the pain without significant unwanted side effects. In this review we focus on recent advances in our knowledge concerning the unique population of primary afferent sensory nerve fibers that innervate the skeleton, the nociceptive and neuropathic mechanisms that are involved in driving skeletal pain, and the neurochemical and structural changes that can occur in sensory and sympathetic nerve fibers and the CNS in chronic skeletal pain. We also discuss therapies targeting nerve growth factor or sclerostin for treating skeletal pain. These therapies have provided unique insight into the factors that drive skeletal pain and the structural decline that occurs in the aging skeleton. We conclude by discussing how these advances have changed our understanding and potentially the therapeutic options for treating and/or preventing chronic pain in the injured, diseased and aged skeleton



CRPS Bugle 10/10/13 | #CRPS

CRPS BugleWelcome to The CRPS Bugle–a selection of recent papers to peruse:

Clin J Pain. 2013 Nov;29(11):e33-e34.

Favorable Outcome of an Acute Complex Regional Pain Syndrome With Immunoglobulin Infusions.

Medlin F, Zekeridou A, Renaud S, Kuntzer T.



To emphasize that complex regional pain syndrome (CRPS), a disabling disorder with the implication of aberrant inflammation, vasomotor dysfunction, and maladaptive neuroplasticity, might be treated with a high dose of intravenous immunoglobulin infusions (IVIG).


We describe a patient who presented with CRPS in the acute phase of the disease.


The CRPS developed secondary to sciatic compression in a young patient and was treated within 10 days by high-dose IVIG (2 g/kg). It resolved completely within days after infusions.


This observational study emphasizes that high-dose IVIG may be a treatment option in the acute phase of CRPS

RS: Interesting but bear in mind that this is a case study with one patient


Ann Intern Med. 2010 Feb 2;152(3):152-8. doi: 10.7326/0003-4819-152-3-201002020-00006.

Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial.

Goebel A, Baranowski A, Maurer K, Ghiai A, McCabe C, Ambler G.


University of Liverpool, Clinical Sciences Building, University Hospital Aintree, Liverpool L9 7AL, United Kingdom.



Treatment of long-standing complex regional pain syndrome (CRPS) is empirical and often of limited efficacy. Preliminary data suggest that the immune system is involved in sustaining this condition and that treatment with low-dose intravenous immunoglobulin (IVIG) may substantially reduce pain in some patients.


To evaluate the efficacy of IVIG in patients with longstanding CRPS under randomized, controlled conditions.


A randomized, double-blind, placebo-controlled crossover trial. (National Research Registry number: N0263177713; International Standard Randomised Controlled Trial Number Registry: 63918259)


University College London Hospitals Pain Management Centre.


Persons who had pain intensity greater than 4 on an 11-point (0 to 10) numerical rating scale and had CRPS for 6 to 30 months that was refractory to standard treatment.


IVIG, 0.5 g/kg, and normal saline in separate treatments, divided by a washout period of at least 28 days.


The primary outcome was pain intensity 6 to 19 days after the initial treatment and the crossover treatment.


13 eligible participants were randomly assigned between November 2005 and May 2008; 12 completed the trial. The average pain intensity was 1.55 units lower after IVIG treatment than after saline (95% CI, 1.29 to 1.82; P < 0.001). In 3 patients, pain intensity after IVIG was less than after saline by 50% or more. No serious adverse reactions were reported.


The trial was small, and recruitment bias and chance variation could have influenced results and their interpretation.


IVIG, 0.5 g/kg, can reduce pain in refractory CRPS. Studies are required to determine the best immunoglobulin dose, the duration of effect, and when repeated treatments are needed.

RS: this study from 2010 demonstrated reduced pain but in a small group


Arch Phys Med Rehabil. 2013 Sep 27

Complex regional pain syndrome type I. Incidence and risk factors in patients with fracture of the distal radius.

Jellad A, Salah S, Frih ZB.


University of Monastir Tunisia, Faculty of Medicine, Department of Physical Medicine and Rehabilitation. Electronic address:



To examine the incidence and predictors of complex regional pain syndrome type I (CRPS I) after fracture of the distal radius.


Prospective study SETTING: University hospital PARTICIPANTS: A consecutive sample of patients (N=90) with fracture of the distal radius treated by closed reduction and casting.


Not applicable MAIN OUTCOME MEASURES: Occurrence of CRPS I, pain, wrist and hand range of motion, radiographic measures, Patient-Rated Wrist Evaluation, Hospital Anxiety and Depression scale and The Short Form 36 at baseline and at 1, 3, 6 and 9 months follow-up.


CRPS I occurred in 29 patients (32.2%) with a mean delay of 21.7±23.7 days from cast removal. Univariate analyses found significant differences between patients with CRPS I and patients without CRPS I at baseline for gender (p=0.021), socio economic level (p=0.023), type of trauma (p=0.05), pain at rest and at activity (p=0.006 and p<0.001), wrist dorsiflexion and pronation (p=0.002 and p=0.001), fingers flexion (p=0.047), thumb opposition (p=0.002), function of the hand (p<0.001), and physical quality of life (p=0.013). Logistic regression showed that risk for CRPS I was higher in cases of female gender (OR:5.774;95%CI:1.391 to 23.966), medium and low energy trauma (OR:7.718;95% CI:1.136 to 52.44), physical quality of life of the short form 36 < 40 (OR:4.931;95%CI:1.428 to 17.025) and patient-rated wrist evaluation pain subscale >16 (OR:12.192;95%CI:4.484 to 43.478).


CRPS I occurs frequently during the third and fourth week after cast removal especially in women who report severe pain and impairment of their physical quality of life. Additional prospective studies are required to verify these findings in comminuted and operated fractures of the distal radius


J Pain. 2013 Sep 21. pii: S1526-5900(13)01130-9. 

Motor Dysfunction of Complex Regional Pain Syndrome Is Related to Impaired Central Processing of Proprioceptive Information.

Bank PJ, Peper CL, Marinus J, Beek PJ, van Hilten JJ.


Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands; Research Institute MOVE, Faculty of Human Movement Sciences, VU University Amsterdam, The Netherlands. Electronic address:


Our understanding of proprioceptive deficits in complex regional pain syndrome (CRPS) and its potential contribution to impaired motor function is still limited. To gain more insight into these issues, we evaluated accuracy and precision of joint position sense over a range of flexion-extension angles of the wrist of the affected and unaffected sides in 25 chronic CRPS patients and in 50 healthy controls. The results revealed proprioceptive impairment at both the patients’ affected and unaffected sides, characterized predominantly by overestimation of wrist extension angles. Precision of the position estimates was more prominently reduced at the affected side. Importantly, group differences in proprioceptive performance were observed not only for tests at identical percentages of each individual’s range of wrist motion but also when controls were tested at wrist angles that corresponded to those of the patient’s affected side. More severe motor impairment of the affected side was associated with poorer proprioceptive performance. Based on additional sensory tests, variations in proprioceptive performance over the range of wrist angles, and comparisons between active and passive displacements, the disturbances of proprioceptive performance most likely resulted from altered processing of afferent (and not efferent) information and its subsequent interpretation in the context of a distorted “body schema.”


The present results point at a significant role for impaired central processing of proprioceptive information in the motor dysfunction of CRPS and suggest that therapeutic strategies aimed at identification of proprioceptive impairments and their restoration may promote the recovery of motor function in CRPS patients.

RS: we know that in many persisting pain cases, especially those with a neuropathic pain mechanism, there is an altered body schema. This must be targeted within the treatment and training programme.

Visit our main clinic page here: Specialist Pain Physio Clinics for persisting pain and injury


Pain metaphors (1)

Story telling | Narrative | MetaphorsA recent comment that I thought summed up several dimensions of the pain experience: ‘my life is contracted’.

Does anyone relate to this?

There can be a physical sense to ‘contraction’ whereby limited movement causes stiffness alongside the tension and guarding that limit mobility and reduce tolerance for activities. Pertinent is the fact that often these activities are the normal day to day pass-times and tasks that one can take for granted, until they become difficult or deemed impossible.

One’s thinking and sensory experience of the World can be ‘contracted’ as the pain becomes all consuming, occupying thoughts and movements to the point that there is little else.

Metaphors that spill from the individual’s thinking and experiences are such valuable insight. Expression of narrative and metaphor should be encouraged and then crafted into different language underpinned by a reconceptualised perspective as the mechanisms of pain and the influences upon pain are discovered and understood.

If you are so inclined, share your thoughts.

RS – Specialist Pain Physio Clinics, London

Pain is a construct | #pain #neuroscience

Pain is a construct that is unique to our own brain hence the individual nature of the experience. By definition, according to the International Association for the Study of Pain (IASP), pain is a sensory and emotional experience. Both sensations and emotions are also brain constructs, in other words our brains create the experience to be played out via the body. In essence this is why pain is so influenced by our mental state and attentional processes: most patients I talk to will describe an increase in pain at times of stress (stress can also reduce pain; stress induced analgesia–this being the case when something else is more salient at the time) and when they are unable to distract themselves.

Our language, pain descriptions, our inner voice are all brain constructs that emerge as are the movements we make–more on this soon

Pain emerges from the body tissues, or in the case of phantom limb pain (PLP) in the space that was once occupied. A great deal has been learned from PLP (see video below with VS Ramachandran talking about ‘The Tell-Tale Brain’) including the fact that pain cannot be created by the tissues as they are clearly not in existence, however the cortical representation (the somatosensory maps, motor maps etc) remain in the brain, igniting under certain circumstances to construct a pain experience via the salient network. The salient network exists to detect differences in physiological activity and respond accordingly, perhaps with protection in mind that would include pain in the area of the body deemed under threat. For pain is about ‘threat’. When the brain receives contextual information suggestive of threat, it must scrutinise this data and compare to what it knows before responding. On there being a perception of threat, regardless of the reality (eg/ light brushing, a simple movement, watching someone else move, thinking about movement–some readers will know only too well how the latter cues can trigger pain), the brain will protect, drive attention and motivate action via the experience of pain in the body.

Our individual belief system, our resilience at the time, our mood at the time and the context will all impact upon the pain perception and what happens next. The construct of pain, the common denominator being that it hurts in the body, is varied in its volume, location and pattern in many cases when the sensitivity has persisted for some time. In other cases, the pain can have a mechanical pattern (not implying that a structure is out of place and can be put back by manual therapy) meaning that certain movements or touch can hurt and be more predictable. However, the bottom line remains that the brain must perceive a threat.

On the positive side, although complex and modulated at many levels, pain is changeable. There are many access routes into changing the experience and a person’s belief that they can gain increasing control over their pain to be able to reduce the feeling and train to decrease sensitivity. The newer brain focused therapies all aim to do this by targeting changes and adaptations in the central nervous system, although I would argue that we are seeking to change the processing of the danger signals with any of the techniques used in the clinic. Light manual techniques that result in pain relief do not ‘put discs back’ but they can alter the threat value and hence change guarding, reflexive protection and the perception of touch leading to relief and ease of movement. We just have to think carefully about which techniques and strategies are most appropriate at the time, how we set the environment and context so that the brain is acceptant of the treatment and responds by reducing activity in the pain matrix or representation.

Undoubtedly treating chronic pain is complex but if we think about the pain mechanisms and the influences upon pain (stress, anxiety, mood, exercise, movement, sleep etc), we can build a comprehensive programme to address the different dimensions: physical, cognitive and emotional. Let us treat the tissues with care to nourish and promote healthy movement, but to do this effectively we have to think about the brain and how it is constructing the reality of the patient and get it onside.

Specialist Pain Physio Clinics, London

CRPS Bugle | #CRPS | Body perception

CRPS BugleWelcome to the latest Bugle that focuses upon body perception, so often affected in CRPS. Body perception should form part of the assessment in my view, as the construction of this sense by the brain is a feature of the condition and must be addressed.

Evaluation of a prototype tool for communicating body perception disturbances in complex regional pain syndrome

Ailie J. Turton, Mark Palmer, Sharon Grieve, Timothy P. Moss, Jenny Lewis and Candida S. McCabe

Patients with Complex Regional Pain Syndrome (CRPS) experience distressing changes in body perception. However representing body perception is a challenge. A digital media tool for communicating body perception disturbances was developed. A proof of concept study evaluating the acceptability of the application for patients to communicate their body perception is reported in this methods paper. Thirteen CRPS participants admitted to a 2-week inpatient rehabilitation program used the application in a consultation with a research nurse. Audio recordings were made of the process and a structured questionnaire was administered to capture experiences of using the tool. Participants produced powerful images of disturbances in their body perception. All reported the tool acceptable for communicating their body perception. Participants described the positive impact of now seeing an image they had previously only imagined and could now convey to others. The application has provided a novel way for communicating perceptions that are otherwise difficult to convey.

* Full article available on the Frontiers in Human Neuroscience website – click here


Eur J Pain. 2012 Oct;16(9):1320-30

Perceptions of the painful body: the relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.

Lewis JS, Schweinhardt P.

Disturbances in body perception are increasingly acknowledged as a feature of complex regional pain syndrome (CRPS). Conventional treatments have limited success particularly among those with long-standing disease. Understanding the relationship between body perception disturbance, pain and tactile acuity might provide insight into alternative avenues for treatment. The aim of this study was to test the hypotheses that (1) body perception disturbance is positively related to pain and (2) decreased tactile acuity is related to increased body perception disturbance.
A controlled observational design was used to measure these features among those with CRPS of one arm. The extent of body perception disturbance was assessed using the Bath CRPS body perception disturbance scale and pain was measured using the neuropathic pain symptom inventory. Two-point discrimination threshold testing was performed as a measure of tactile acuity.
Findings confirmed both hypotheses. Body perception disturbance was found to positively correlate with pain such that those in greater pain had more extensive body perception disturbance (r = 0.57, p < 0.01). Furthermore, a positive correlation was revealed between body perception disturbance and two-point discrimination thresholds (r = 0.5, p < 0.025) so those with greater body perception disturbance had worse tactile acuity. Interestingly, those with longer disease duration had significantly greater body perception disturbance (r = 0.66, p < 0.001).
Aberrant central processing is suggested as the neural correlate of body perception disturbance and tactile impairment. The exact relationship between body perception disturbance, pain and tactile acuity and how they may be modulated for pain relief requires further exploration.


Pain. 2012 Nov;153(11):2174-81

Impaired spatial body representation in complex regional pain syndrome type 1 (CRPS I).

Reinersmann A, Landwehrt J, Krumova EK, Ocklenburg S, Güntürkün O, Maier C.

Recently, a shift of the visual subjective body midline (vSM), a correlate of the egocentric reference frame, towards the affected side was reported in patients with complex regional pain syndrome (CRPS). However, the specificity of this finding is as yet unclear. This study compares 24 CRPS patients to 21 patients with upper limb pain of other origin (pain control) and to 24 healthy subjects using a comprehensive test battery, including assessment of the vSM in light and dark, line bisection, hand laterality recognition, neglect-like severity symptoms, and motor impairment (disability of the arm, shoulder, and hand). Statistics: 1-way analysis of variance, t-tests, significance level: 0.05. In the dark, CRPS patients displayed a significantly larger leftward spatial bias when estimating their vSM, compared to pain controls and healthy subjects, and also reported lower motor function than pain controls. For right-affected CRPS patients only, the deviation of the vSM correlated significantly with the severity of distorted body perception. Results confirm previous findings of impaired visuospatial perception in CRPS patients, which might be the result of the involvement of supraspinal mechanisms in this pain syndrome. These mechanisms might accentuate the leftward bias that results from a right-hemispheric dominance in visuospatial processing and is known as pseudoneglect. Pseudoneglect reveals itself in the tendency to perceive the midpoint of horizontal lines or the subjective body midline left of the centre. It was observable in all 3 groups, but most pronounced in CRPS patients, which might be due to the cortical reorganisation processes associated with this syndrome.


Specialist Pain Physio Clinics, London

Endometriosis & Melatonin | Women and Pain Series

Endometriosis pain

Many individuals who I see with CRPS and other chronically painful conditions will describe other problems that seemingly involve other body systems. However, there is commonality in the sensitisation that arises and is expreseed in different ways. The range of complaints falls under the ‘functional pain syndrome’ banner and includes irritable bowel syndrome, migraine, chronic widespread pain, bladder dysfunction, jaw pain and pelvic pain. Here we look at one problem that can include pelvic pain, endometriosis.

Chronic pelvic pain is a troubling condition for many women. The reason for pelvic pain varies but certainly includes endometriosis where the lesions impact upon nerve health and function (see here) with consequential sensitisation. The purported mechanisms of pain include inflammatory pain and neuropathic pain with subsequent central sensitisation that underpins the persistance and variance often described – see full article here

Pain is an output, a response to the brain’s perception of what is happening in the body. The sensation of pain emerges from that part of the body deemed in need of protection. The pain itself is modulated by a range of factors including stress, fatigue, anxiety and the environment. The actual feeling of pain is the end result of the brain’s analysis of what is going on ‘now’ on the basis of what it already knows and has learned. Hence, prior experience can flavour the pain. Changes in the spinal cord and higher centres can amplify danger signals, modulate normal signals (begin as normal and communicate with nociceptors, therefore the brain receives a danger signal despite the initiating impulse being one of touch; i.e./ allodynia) and are responsible for the varying patterns of pain such as when a treatment helps on one occasion yet seemingly worsens the pain on a subsequent occasion.

Alongside the painful experience there are other body and brain responses to the perceived threat. Altered control of movement that includes guarding and protective posturing that leads to patterns of on-going chronic tension. In the case of pelvic pain this emerges around the pelvic girdle, in the abdomen and in the spinal muscles and often across the body. It is not unusual to find that there are many tender and tight areas when the body has been protected for some time, demonstrating a more widespread pattern. Often there is sensitivity expressed via other body systems , for example the gastrointestinal system in IBS, headaches, migraine and recurring bladder infections to name but a few. General health can often be impacted upon, with levels of activity diminishing alongside a fear of moving and socialising (a gradual withdrawal from being out with friends and family). This typically leads to a downward spiral affecting mood, self-esteem and manifesting with anxiety in many situations. It is really a ‘hyper-protective’ state physically and mentally where many cues become threatening and hence we protect, sometimes consciously by making choices and frequently automatically or habitually. Breaking this pattern however, is entirely possible.

We are fundamentally designed to change, evolve and grow. When we set the right conditions physically and mentally (and it has to be both), then we can move forward and change our outlook and experience. I know that an individual is going to progress when they start changing their language, metaphor use and at the same time their appearance changes via posture, facial expression and general demeanour. The spark returns.

The optimal approach requires that we consider all the dimensions of pain: physical, cognitive and emotional. This must be integrated and a programme (click here) created to meet the unique needs of the person. Concomitant with a range of strategies and training techniques to retrain normal movement, tension patterns, ease pain, tackle stress and anxiety etc, medication can play a role. The efficacy of pain medication is varied and often there are side-effects to consider. A recent study looked at the use of melatonin for endometriosis-associated pain with some very interesting results.

The commentary of Timothy Ness in Pain 154 (2013) 775 summarises the study below: ‘The article by Schwertner et al..demonstrated efficacy of the hormone, melatonin, in the treatment of endometriosis-associated pain… of the few medications which have proven useful in the treatment of endometriosis-associated pelvic pain but it is also notable as an example of the back-and-forth translational process associated with preclinical models of pain/analgesia and the clinical demonstration of treatment efficacy.’ And, ‘In this particular example the information flow went in both directions from humans to non-humans and then back again’. He refers to the fact that the data produced in rats was also found in humans. Many studies use rodents as subjects with obvious limitations in terms of extrapolating data for humans.

Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial.

Pain. 2013 Jun;154(6):874-81.

Schwertner A, Conceição Dos Santos CC, Costa GD, Deitos A, de Souza A, de Souza IC, Torres IL, da Cunha Filho JS, Caumo W.


Laboratory of Pain & Neuromodulation at Hospital de Clínicas de Porto Alegre (HCPA)/Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.


Endometriosis-associated chronic pelvic pain (EACPP) presents with an intense inflammatory reaction. Melatonin has emerged as an important analgesic, antioxidant, and antiinflammatory agent. This trial investigates the effects of melatonin compared with a placebo on EACPP, brain-derived neurotrophic factor (BDNF) level, and sleep quality. Forty females, aged 18 to 45 years, were randomized into the placebo (n = 20) or melatonin (10 mg) (n = 20) treatment groups for a period of 8 weeks. There was a significant interaction (time vs group) regarding the main outcomes of the pain scores as indexed by the visual analogue scale on daily pain, dysmenorrhea, dysuria, and dyschezia (analysis of variance, P < 0.01 for all analyses). Post hoc analysis showed that compared with placebo, the treatment reduced daily pain scores by 39.80% (95% confidence interval [CI] 12.88-43.01%) and dysmenorrhea by 38.01% (95% CI 15.96-49.15%). Melatonin improved sleep quality, reduced the risk of using an analgesic by 80%, and reduced BNDF levels independently of its effect on pain. This study provides additional evidence regarding the analgesic effects of melatonin on EACPP and melatonin’s ability to improve sleep quality. Additionally, the study revealed that melatonin modulates the secretion of BDNF and pain through distinct mechanisms.

For further information about our proactive treatment, training and coaching programmes for chronic pain and injury, or to book an appointment please call us on 07932 689081 | Women in Pain Clinic in Harley Street


J Pain Symptom Manage. 2012 Nov 27.

Analgesic and Sedative Effects of Melatonin in Temporomandibular Disorders: A Double-Blind, Randomized, Parallel-Group, Placebo-Controlled Study.

Vidor LP, Torres IL, de Souza IC, Fregni F, Caumo W.


Postgraduate Program in Medical Sciences, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.



The association between myofascial temporomandibular disorder (TMD) and nonrestorative sleep supports the investigation of therapies that can modulate the sleep/wake cycle. In this context, melatonin becomes an attractive treatment option for myofascial TMD pain.


To investigate the effects of melatonin on pain (primary aim) and sleep (secondary aim) as compared with placebo in a double-blind, randomized, parallel-group trial.


Thirty-two females, aged 20-40 years, with myofascial TMD pain were randomized into placebo or melatonin (5mg) treatment groups for a period of four weeks.


There was a significant interaction (time vs. group) for the main outcomes of pain scores as indexed by the visual analogue scale and pressure pain threshold (analysis of variance; P<0.05 for these analyses). Post hoc analysis showed that the treatment reduced pain scores by -44% (95% CI -57%, -26%) compared with placebo, and it also increased the pressure pain threshold by 39% (95% CI 14%, 54%). The use of analgesic doses significantly decreased with time (P<0.01). The daily analgesic doses decreased by -66% (95% CI -94%, -41%) when comparing the two groups. Additionally, melatonin improved sleep quality, but its effect on pain was independent of the effect on sleep quality.


This study provides additional evidence supporting the analgesic effects of melatonin on pain scores and analgesic consumption in patients with mild-to-moderate chronic myofascial TMD pain. Furthermore, melatonin improves sleep quality but its effect on pain appears to be independent of changes in sleep quality.

CRPS Bugle 13 Aug #CRPS

CRPS BugleWelcome to the latest CRPS Bugle


Acute and chronic phases of complex regional pain syndrome in mice are accompanied by distinct transcriptional changes in the spinal cord.

Mol Pain. 2013 Aug 8;9(1):40.

Gallagher JJ, Tajerian M, Guo T, Shi X, Li W, Zheng M, Peltz G, Kingery W, Clark JD.



CRPS is a painful, debilitating, and often-chronic condition characterized by various sensory, motor, and vascular disturbances. Despite many years of study, current treatments are limited by our understanding of the underlying mechanisms. Little is known on the molecular level concerning changes in gene expression supporting the nociceptive sensitization commonly observed in CRPS limbs, or how those changes might evolve over time.


We used a well-characterized mouse tibial fracture/cast immobilization model of CRPS to study molecular, vascular and nociceptive changes. We observed that the acute (3 weeks after fracture) and chronic (7 weeks after fracture) phases of CRPS-like changes in our model were accompanied by unique alterations in spinal gene expression corresponding to distinct canonical pathways. For the acute phase, top regulated pathways were: chemokine signaling, glycogen degradation, and cAMP-mediated signaling; while for the chronic phase, the associated pathways were: coagulation system, granzyme A signaling, and aryl hydrocarbon receptor signaling. We then focused on the role of CcL2, a chemokine that we showed to be upregulated at the mRNA and protein levels in spinal cord tissue in our model. We confirmed its association with the nociceptive sensitization displayed in this model by demonstrating that the spinal but not peripheral administration of a CCR2 antagonist (RS504393) in CRPS animals could decrease mechanical allodynia. The spinal administration of CcL2 itself resulted in mechanical allodynia in control mice.


Our data provide a global look at the transcriptional changes in the spinal cord that accompany the acute and chronic phases of CRPS as modeled in mice. Furthermore, it follows up on one of the top-regulated genes coding for CcL2 and validates its role in regulating nociception in the fracture/cast model of CRPS.


An older paper identifying the effects of immobilisation that are similar to CRPS and the role of substance P in the vascular changes.

Substance P signalling contributes to the vascular and nociceptive abnormalities observed in a tibial fracture rat model of complex regional pain syndrome type I.

Pain. 2004 Mar;108(1-2):95-107.

Guo TZ, Offley SC, Boyd EA, Jacobs CR, Kingery WS.


Physical Medicine and Rehabilitation Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.


Wrist and ankle fractures are the most frequent causes of complex regional pain syndrome (CRPS type I). The current study examined the temporal development of vascular, nociceptive and bony changes after distal tibial fracture in rats and compared these changes to those observed after cast immobilization in intact normal rats. After baseline testing the right distal tibial was fractured and the hindlimb casted. A control group was simply casted without fracturing the tibia. After 4 weeks the casts were removed and the rats retested. Subsequent testing was performed at 6, 8, 10, 16, and 20 weeks after onset of treatment. Distal tibial fracture or cast immobilization alone generated chronic hindlimb warmth, edema, spontaneous protein extravasation, allodynia, and periarticular osteoporosis, changes resembling those observed in CRPS. Hindlimb warmth and allodynia resolved much more quickly after cast immobilization than after fracture. Previously we observed that the substance P receptor (NK(1)) antagonist LY303870 reversed vascular and nociceptive changes in a sciatic section rat model of CRPS type II. Postulating that facilitated substance P signaling may also contribute to the vascular and nociceptive abnormalities observed after tibial fracture or cast immobilization, we attempted to reverse these changes with LY303870. Hindpaw warmth, spontaneous extravasation, edema, and allodynia were inhibited by LY303870. Collectively, these data support the hypotheses that the distal tibial fracture model simulates CRPS, immobilization alone can generate a syndrome resembling CRPS, and substance P signaling contributes to the vascular and nociceptive changes observed in these models.


Pain-related fear, perceived harmfulness of activities, and functional limitations in complex regional pain syndrome type I.

J Pain. 2011 Dec;12(12):1209-18. doi: 10.1016/j.jpain.2011.06.010.

de Jong JR, Vlaeyen JW, de Gelder JM, Patijn J.


Department of Rehabilitation, University Hospital Maastricht, Maastricht, The Netherlands.


Numerous studies have shown that pain-related fear is one of the strongest predictors of pain disability in patients with chronic musculoskeletal pain, and there is evidence that the reduction of pain-related fear through an exposure treatment can be associated with restoration of functional abilities in patients with complex regional pain syndrome type I (CRPS-I). These findings suggest that pain-related fear may be associated with functional limitations in neuropathic pain as well. The aim of the current study was to test whether the debilitating role of pain-related fear generalizes to patients with CRPS-I. The results of 2 studies are presented. Study I includes a sample of patients with early CRPS-I referred to an outpatient pain clinic. In Study II, patients with chronic CRPS who are members of a patients’ association were invited to participate. The results show that in early CRPS-I, pain severity but not fear of movement/(re)injury as measured with the Tampa Scale for Kinesiophobia was related to functional limitations. In patients with chronic CRPS-I, however, perceived harmfulness of activities as measured with the pictorial assessment method significantly predicted functional limitations beyond and above the contribution of pain severity. Not fear of movement/(re)injury in general, but the perceived harmfulness of activities appears a key factor that might be addressed more systematically in the clinical assessment of patients with CRPS-I. These results support the idea that pain-related fear might be a promising concept in the understanding of pain disability in patients with neuropathic pain.


This is the first study showing that perceived harmfulness of activities contribute to the functional limitations in CRPS-I. The current findings may help clinicians customizing cognitive-behavioral treatments for patients with chronic neuropathic pain.


Please visit our clinic site for further information on treatment, training & coaching for CRPS (RSD): Specialist Pain Physio Clinics, London or call us on 07932 689081

#CRPS Bugle | 28th July

CRPS BugleImpaired Recognition of Social Emotion in Patients With Complex Regional Pain Syndrome.

J Pain. 2013 Jul 19.

Shin NY, Kang DH, Jang JH, Park SY, Hwang JY, Kim SN, Byun MS, Park HY, Kim YC.


Multiple brain areas involved in nociceptive, autonomic, and social-emotional processing are disproportionally changed in patients with complex regional pain syndrome (CRPS). Little empirical evidence is available involving social cognitive functioning in patients with chronic pain conditions. We investigated the ability of patients with CRPS to recognize the mental/emotional states of other people. Forty-three patients with CRPS and 30 healthy controls performed the Reading Mind in the Eyes Test, which consists of photos in which human eyes express various emotional and mental states. Neuropsychological tests, including the Wisconsin Card Sorting Test, the stop-signal test, and the reaction time test, were administered to evaluate other cognitive functions. Patients with CRPS were significantly less accurate at recognizing emotional states in other persons, but not on other cognitive tests, compared with control subjects. We found a significant association between the deficit in social-emotion recognition and the affective dimension of pain, whereas this deficit was not related to the sensory dimension of pain. Our findings suggest a disrupted ability to recognize others’ mental/emotional states in patients with CRPS.


This article demonstrated a deficit in inferring mental/emotional states of others in patients with CRPS that was related to pain affect. Our study suggests that additional interventions directed toward reducing distressful affective pain may be helpful to restore social cognitive processing in patients with CRPS.

RS – addressing all the dimensions of pain is vital in a comprehensive treatment & training programme: physical, emotional & cognitive. Awareness of deficits such as ‘inferring mental/emotional states of others’, as seen in this study, allows clinicians to account for certain behaviours and responses that can be seen during the assessment process and treatment sessions. Subsequently, the therapy choice can be made on an individual basis to target the deficits.


Altered Resting-State Functional Connectivity in Complex Regional Pain Syndrome.

J Pain. 2013 Jun 18.

Bolwerk A, Seifert F, Maihöfner C.


This study explored the functional connectivity between brain regions implicated in the default mode network, the sensorimotor cortex (S1/M1), and the intraparietal sulcus (IPS/MIP) at rest in patients with complex regional pain syndrome. It also investigated how possible alterations are associated with neuropathic pain. Our group used functional magnetic resonance imaging to investigate functional brain connectivity in 12 complex regional pain syndrome patients in comparison with that in 12 age- and sex-matched healthy controls. Data were analyzed using a seed voxel correlation analysis and an independent component analysis. An analysis of covariance was employed to relate alterations in functional connectivity with clinical symptoms. We found significantly greater reductions in functional default mode network connectivity in patients compared to controls. The functional connectivity maps of S1/M1 and IPS/MIP in patients revealed greater and more diffuse connectivity with other brain regions, mainly with the cingulate cortex, precuneus, thalamus, and prefrontal cortex. In contrast, controls showed greater intraregional connectivity within S1/M1 and IPS/MIP. Furthermore, there was a trend for correlation between alterations in functional connectivity and intensity of neuropathic pain. In our findings, patients with complex regional pain syndrome have substantial spatial alterations in the functional connectivity between brain regions implicated in the resting-state default mode network, S1/M1, and IPS/MIP; these alterations show a trend of correlation with neuropathic pain intensity.


This article presents spatial alterations in the functional resting-state connectivity of complex regional pain syndrome patients. Our results add further insight into the disease states of CRPS and into the functional architecture of the resting state brains of pain patients in general.

RS: Pain emerges from the body. That is where we feel it undoubtedly. It can be a difficult leap to understand that the neural correlate sits within the brain. There is no pain centre but rather a widespread group of neurons in different brain regions that when activated, create a neurotag or neurosignature that manifests as pain where the brain perceives a threat that requires protection. It is no surprise therefore, to see a further study highlight altered activity within the brain in CRPS patients compared to a control group. From a clinical perspective, it demonstrates that we have to ‘think brain’ within the reasoning behind the design of a rehabilitation programme and in appropriate cases use therapies such as graded motor imagery


A Disturbance in Sensory Processing on the Affected Side of the Body Increases Limb Pain in Complex Regional Pain Syndrome.

Clin J Pain. 2013 Jun 19.

Drummond PD, Finch PM.



The aim of this study was to determine whether a central disturbance in somatosensory processing contributes to limb pain in complex regional pain syndrome (CRPS).


In 37 patients with CRPS, the effect of cooling the ipsilateral forehead on pain in the affected limb was compared with the effect of cooling the contralateral forehead. In addition, symptoms associated with cold-evoked limb pain were explored.


Limb pain generally increased when the ipsilateral side of the forehead was cooled but did not change when the contralateral side of the forehead was cooled. Increases were greatest in patients with heightened sensitivity to cold, brushing, and pressure-pain in the ipsilateral forehead, in patients with heightened sensitivity to pressure-pain in the limbs, and in patients with chronic symptoms. In contrast, sensitivity to light touch was diminished in the CRPS-affected limb of patients whose limb pain remained unchanged or decreased during ipsilateral forehead cooling.


These preliminary findings suggest that a central disturbance in sensory processing and pain modulation, which extends beyond the affected limb to the ipsilateral forehead, contributes to symptoms in a subgroup of patients with CRPS.

RS: A number of patients who present with pain that is underpinned by a component of central sensitisation will also, being given the chance, describe pain in other body regions and body systems. Being vigilant to this possibility is fundamental to a complete assessment, the conclusions of which will guide the treatment programme.


Local cytokine changes in complex regional pain syndrome type I (CRPS I) resolve after 6months.

Pain. 2013 Jun 27.

Lenz M, Uçeyler N, Frettlöh J, Höffken O, Krumova EK, Lissek S, Reinersmann A, Sommer C, Stude P, Waaga-Gasser AM, Tegenthoff M, Maier C.


There is evidence that inflammatory processes are involved in at least the early phase of complex regional pain syndrome (CRPS). We compared a panel of pro- and antiinflammatory cytokines in skin blister fluids and serum from patients with CRPS and patients with upper-limb pain of other origin (non-CRPS) in the early stage (< 1year) and after 6months of pain treatment. Blister fluid was collected from the affected and contralateral nonaffected side. We used a multiplex-10 bead array cytokine assay and Luminex technology to measure protein concentrations of the cytokines interleukin-1 receptor antagonist (IL-1RA), IL-2, IL-6, IL-8, IL-10, IL-12p40, and tumor necrosis factor-alpha (TNF-α) and the chemokines eotaxin, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1β (MIP-1β). We found bilaterally increased proinflammatory TNF-α and MIP-1β and decreased antiinflammatory IL-1RA protein levels in CRPS patients compared to non-CRPS patients. Neither group showed side differences. After 6 months under analgesic treatment, protein levels of all measured cytokines in CRPS patients, except for IL-6, significantly changed bilaterally to the level of non-CRPS patients. These changes were not related to treatment outcome. In serum, only IL-8, TNF-α, eotaxin, MCP-1, and MIP-1β were detectable without intergroup differences. Blister fluid of CRPS patients showed a bilateral proinflammatory cytokine profile. This profile seems to be relevant only at the early stage of CRPS. Almost all measured cytokine levels were comparable to those of non-CRPS patients after 6 months of analgesic treatment and were not related to treatment outcome.

RS: ‘Blister fluid of CRPS patients showed a bilateral proinflammatory cytokine profile. This profile seems to be relevant only at the early stage of CRPS’. In some patients there is an inflammatory profile that should be noted and treated as early as possible. On-going inflammation will cause a persisting bombardment of danger signals to the spinal cord and to the higher centres. The brain does want to know about inflammation and when detected it typically hurts, the purpose being that we need to know (consciously) so that we take appropriate action. Tackling inflammation early may have a beneficial effect upon this process.


Limb-specific autonomic dysfunction in complex regional pain syndrome modulated by wearing prism glasses.

Pain. 2013 Jul 22.

Lorimer Moseley G, Gallace A, Di Pietro F, Spence C, Iannetti GD.


In unilateral upper limb complex regional pain syndrome (CRPS), the temperature of the hands is modulated by where the arms are located, relative to the body midline. We hypothesized that this effect depends on the perceived location of the hands, not on their actual location, nor on their anatomical alignment. In two separate cross-sectional randomized experiments, ten (6 female) unilateral CRPS patients wore prism glasses that laterally shifted the visual field by 20°. Skin temperature was measured before and after nine-minute periods in which the position of one hand was changed. Placing the affected hand on the healthy side of the body midline increased its temperature (Δ°C =0.47 ± 0.14°C), but not if prism glasses made the hand appear to be on the body midline (Δ°C =0.07 ± 0.06°C). Similarly, when prism glasses made the affected hand appear to be on the healthy side of the body midline, even though it was not, the affected hand warmed up (Δ°C =0.28 ± 0.14°C). When prism glasses made the healthy hand appear to be on the affected side of the body midline, even though it was not, the healthy hand cooled down (Δ°C = -0.30 ± 0.15°C). Friedman’s ANOVA and Wilcoxon’s pairs tests upheld the results (p <0.01 for all). We conclude that, in CRPS, cortical mechanisms responsible for encoding the perceived location of the limbs in space modulate the temperature of the hands.

And, another paper here:

Spatially defined modulation of skin temperature and hand ownership of both hands in patients with unilateral complex regional pain syndrome.

Brain. 2012 Dec;135(Pt 12):3676-86.

Moseley GL, Gallace A, Iannetti GD.


Numerous clinical conditions, including complex regional pain syndrome, are characterized by autonomic dysfunctions (e.g. altered thermoregulation, sometimes confined to a single limb), and disrupted cortical representation of the body and the surrounding space. The presence, in patients with complex regional pain syndrome, of a disruption in spatial perception, bodily ownership and thermoregulation led us to hypothesize that impaired spatial perception might result in a spatial-dependent modulation of thermoregulation and bodily ownership over the affected limb. In five experiments involving a total of 23 patients with complex regional pain syndrome of one arm and 10 healthy control subjects, we measured skin temperature of the hand with infrared thermal imaging, before and after experimental periods of either 9 or 10 min each, during which the hand was held on one or the other side of the body midline. Tactile processing was assessed by temporal order judgements of pairs of vibrotactile stimuli, delivered one to each hand. Pain and sense of ownership over the hand were assessed by self-report scales. Across experiments, when kept on its usual side of the body midline, the affected hand was 0.5 ± 0.3°C cooler than the healthy hand (P < 0.02 for all, a common finding in cold-type complex regional pain syndrome), and tactile stimuli delivered to the healthy hand were prioritized over those delivered to the affected hand. Simply crossing both hands over the midline resulted in (i) warming of the affected hand (the affected hand became 0.4 ± 0.3°C warmer than when it was in the uncrossed position; P = 0.01); (ii) cooling of the healthy hand (by 0.3 ± 0.3°C; P = 0.02); and (iii) reversal of the prioritization of tactile processing. When only the affected hand was crossed over the midline, it became warmer (by 0.5 ± 0.3°C; P = 0.01). When only the healthy hand was crossed over the midline, it became cooler (by 0.3 ± 0.3°C; P = 0.01). The temperature change of either hand was positively related to its distance from the body midline (pooled data: r = 0.76, P < 0.001). Crossing the affected hand over the body midline had small but significant effects on both spontaneous pain (which was reduced) and the sense of ownership over the hand (which was increased) (P < 0.04 for both). We conclude that impaired spatial perception modulated temperature of the limbs, tactile processing, spontaneous pain and the sense of ownership over the hands. These results show that complex regional pain syndrome involves more complex neurological dysfunction than has previously been considered.

RS: very cool research unravelling the complex mechanisms that underpin CRPS

Come and visit our clinic site here: Specialist Pain Physio Clinics, London for treatment and training for complex and chronic pain