Tag Archives: complex regional pain syndrome London

14Sep/11

Neuropathic pain Update

I have looked at recent papers that focus on neuropathic pain, one of the common pain types seen in CRPS. I’m afraid that some of the research is ‘sciency’ but of course it has to be, so do not worry of you don’t fully understand the methods or the physiology. At the end of the more complex abstracts I have put a summary.

Science. 2011 Sep 9;333(6048):1462-6.

HCN2 ion channels play a central role in inflammatory and neuropathic pain.

Emery EC, Young GT, Berrocoso EM, Chen L, McNaughton PA.

Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.

The rate of action potential firing in nociceptors is a major determinant of the intensity of pain. Possible modulators of action potential firing include the HCN ion channels, which generate an inward current, I(h), after hyperpolarization of the membrane. We found that genetic deletion of HCN2 removed the cyclic adenosine monophosphate (cAMP)-sensitive component of I(h) and abolished action potential firing caused by an elevation of cAMP in nociceptors. Mice in which HCN2 was specifically deleted in nociceptors expressing Na(V)1.8 had normal pain thresholds, but inflammation did not cause hyperalgesia to heat stimuli. After a nerve lesion, these mice showed no neuropathic pain in response to thermal or mechanical stimuli. Neuropathic pain is therefore initiated by HCN2-driven action potential firing in Na(V)1.8-expressing nociceptors.

The excitability of a nerve is determined by the activity of receptors that allow ions to flow in and out. The flow of ions alters the threshold of excitability meaning that it is much easier for the nerve to be stimulated and fire a signal. It is the firing of danger signals to the brain via the spinal cord that can lead to pain. When I say that it ‘can’ lead to pain, this is because sometimes the brain receives these danger signals but does not respond by producing pain. The brain must judge the signals to be a sign of danger for pain to be experienced. Neuropathic pain often includes spontaneous pain that is caused by ectopic firing of signals.

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Pain Med. 2011 Sep 7. doi: 10.1111/j.1526-4637.2011.01227.x. [Epub ahead of print]

The Influence of Chinook Winds and Other Weather Patterns upon Neuropathic Pain.

Ngan S, Toth C.

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.

Objective.   Although Chinook winds are often viewed positively during a cold prairie winter, patients suffering with neuropathic pain (NeP) anecdotally report exacerbations of NeP during Chinooks and during other weather changes. Our objective was to identify if Chinook winds lead to acute exacerbations in pain severity in a NeP patient population. Design.  Prospective diary-based assessments of patients with at least moderate NeP over 6-month periods during different seasons of the year were performed. Concurrent weather conditions were tracked hourly, with Chinook winds defined using accepted meteorological definition. We also examined other aspects of weather including precipitation, temperature, and humidity. Days with acute exacerbations were defined when a daily visual analog score pain score was ≥2 points above their average NeP score over the entire 6-month period. Results.  Chinooks were not associated with individual acute exacerbations in NeP. Instead, Chinook days were found to be protective against acute exacerbations in NeP (odds ratio 0.52 [0.33-0.71]). Post hoc study associated Chinooks with NeP relief (odds ratio 1.83 [1.17-2.49]). We could not identify relationship between precipitation or humidity with acute NeP exacerbation. However, days with cold temperature ≤ -14°C were associated with greater risk of NeP exacerbation. Conclusion.  Weather-mediated changes occur for patients with NeP, manifesting as relief from Chinook winds while cold temperature conditions can provoke exacerbations in NeP.

Cold commonly affects neuropathic pain–worsening the symptomsincluding ambient temperature or a cold stimulus applied (e.g. alcohol wipe, cold draft, ice)

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Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007076.

Pregabalin for acute and chronic pain in adults.

Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ.

Pain Research and Nuffield Department of Anaesthetics, University of Oxford, West Wing (Level 6), John Radcliffe Hospital, Oxford, Oxfordshire, UK, OX3 9DU.

BACKGROUND:

Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions.

OBJECTIVES:

To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain.

SEARCH STRATEGY:

We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified from the reference lists of retrieved papers and on-line clinical trial databases.

SELECTION CRITERIA:

Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome.

DATA COLLECTION AND ANALYSIS:

Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals.

MAIN RESULTS:

There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic nociceptive pain, like arthritis.Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose. The best (lowest) NNT for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia.With 600 mg pregabalin daily somnolence typically occurred in 15% to 25% and dizziness occurred in 27% to 46%. Treatment was discontinued due to adverse events in 18 to 28%. The proportion of participants reporting at least one adverse event was not affected by dose, nor was the number with a serious adverse event, which was not more than with placebo.Higher rates of substantial benefit were found in postherpetic neuralgia and painful diabetic neuropathy than in central neuropathic pain and fibromyalgia. For moderate and substantial benefit on any outcome NNTs for the former were generally six and below for 300 mg and 600 mg daily; for fibromyalgia NNTs were much higher, and generally seven and above.

AUTHORS’ CONCLUSIONS:

Pregabalin has proven efficacy in neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events. Individualisation of treatment is needed to maximise pain relief and minimise adverse events. There is no evidence to support the use of pregabalin in acute pain scenarios.

This is a Cochrane Review meaning that a number of research papers are analysed before concluding whether a treatment is effective or not.

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Pain. 2011 Aug 27. [Epub ahead of print]

Genotype-selective phenotypic switch in primary afferent neurons contributes to neuropathic pain.

Nitzan-Luques A, Devor M, Tal M.

Department of Medical Neurobiology, Faculties of Medicine and Dentistry, The Hebrew University of Jerusalem, Jerusalem, Israel.

Pain is normally mediated by nociceptive Aδ and C fibers, while Aβ fibers signal touch. However, after nerve injury, Aβ fibers may signal pain–this means that touch now hurts. Using a genetic model, we tested the hypothesis that phenotypic switching in neurotransmitters expressed by Aβ afferents might account for heritable differences in neuropathic pain behavior. The study examined selection-line rats in which one line, high autotomy (HA)rats chewing themselves as  a pain behaviour–, shows higher levels of spontaneous pain in the neuroma neuropathy model, and of tactile allodynia in the spinal nerve ligation (SNL) model, than the companion low autotomy (LA) line. Changes in calcitonin gene-related peptide (CGRP) and Substance Ppeptides released by cells that cause excitability– expression were evaluated immunohistochemically in L4 and L5 dorsal root ganglia 7days after SNL surgery. Expression of CGRP was decreased in axotomized small- and medium-diameter neurons in both rat lines. However, in HA but not in LA rats, there was a tenfold increase in CGRP immunoreactivity (CGRP-IR) in large-diameter neurons. Corresponding changes in CGRP-IR in axon terminals in the nucleus gracilis were also seen. Finally, there were indications of enhanced CGRP neurotransmission in deep laminae of the dorsal horn. Substance P immunoreactivity was also upregulated in large-diameter neurons, but this change was similar in the 2 lines. Our findings suggest that phenotypic switching contributes to the heritable difference in pain behavior in HA vs LA rats. Specifically, we propose that in HA rats, but less so in LA rats, injured, spontaneously active Aβ afferents both directly drive CGRP-sensitive central nervous system pain-signaling neurons and also trigger and maintain central sensitization, hence generating spontaneous pain and tactile allodynia.

Spontaneous pain and pain from light touch is due to genetic changes in the nerve cells of Aß afferent (sensory) nerves.

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A classic paper

Neurology. 2008 Apr 29;70(18):1630-5. Epub 2007 Nov 14.

Neuropathic pain: redefinition and a grading system for clinical and research purposes.

Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, Hansson P, Hughes R, Nurmikko T, Serra J.

Institute of Physiology and Pathophysiology, Johannes Gutenberg University, Mainz, Germany.

Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as “pain initiated or caused by a primary lesion or dysfunction in the nervous system.” While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes.

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Application

In my view there are many cases of neuropathic pain (NP) that are not identified, mainly because the examiner is not looking for this pain type. This paper considers whether NP exists in anterior knee pain–it does in my experience. I see a large number of people with back complaints and is it not uncommon to find NP hiding in there, often obscured by a more mechanical or inflammatory pain mechanism. Using clinical tests and a measure or two, we can convert suspicion to reality and then consider how this pain type needs to be managed. There are different implications when NP is present including the prognosis. It takes longer to settle down and flare-ups are common. Flare-ups need effective management including self-care strategies to move through these difficultly times effectively. RS

Clin J Pain. 2008 Jun;24(5):384-94.

Is pain in patellofemoral pain syndrome neuropathic?

Jensen R, Kvale A, Baerheim A.

Section for Physiotherapy Science, Department of Public Health and Primary Health Care, University of Bergen, Kalfarveien, Bergen, Norway. [email protected]

There is no consensus among experts regarding the etiology or management of patellofemoral pain syndrome (PFPS). Observations indicating dysfunction of the peripheral nervous system around the patellae have been reported. To what extent these sensory abnormalities cause pain has so far not been investigated. The aim of this study was to assess whether a subgroup of patients with unilateral PFPS have neuropathic pain related to the painful knee.

METHOD:

A total of 91 patients with unilateral PFPS, between 18 and 40 years of age, and a comparable group of 23 healthy participants aged 18 to 44 years were included. Level of knee function, pain intensity, and qualities were assessed. Somatosensory assessments were carried out by bedside neurologic tests and quantitative sensory testing, assessing thermal, tactile, and vibration thresholds.

RESULTS:

Ample signs of sensory aberrations with considerable heterogeneity and overlap regarding the degree and type of dysfunction of the nervous system were found in the painful area of the PFPS patients. No clear subgroup of patients with neuropathic pain or clustering of features related to neuropathic pain was identified.

DISCUSSION:

This study hypothesizes that the observed sensory aberrations may cause neuropathic pain in patients with PFPS. There is no validated method for subgrouping patients with possible neuropathic pain and in this study considerable heterogeneity and overlap regarding signs and symptoms of neuropathic pain made subgrouping even more difficult. A mechanism-based understanding of the pain is, however, essential for the selection of adequate treatment strategies in painful musculoskeletal disorders.


19Apr/11
Hands of God & Adam

Complex Regional Pain Syndrome (CRPS/RSD)

Complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy (RSD), is undoubtedly a nasty condition in many cases. It can be hugely disruptive in the desire to lead a normal and fulfilling life due the experience of sheer pain and the difficulty in doing day to day activities.

I hear a huge range of stories of how the problem began and how it has been treated. Sometimes there is a significant injury, but often it is the type of event that one would associate with recovery such as an ankle sprain, a knocked elbow or a fracture. Unfortunately in a number of cases this simply does not happen. The injury is sustained, the area usually hurts as you would expect but then it continues to hurt and gets worse. There are associated signs and symptoms such as colour change, temperature change, altered sensation (pins and needles, numbness), an altered sense of position, a feeling of ‘largeness’, ‘thickened’ skin, huge sensitivity to light touch (allodynia), changes in skin, hair and nails. Fortunately we understand much more about the underlying mechanisms and can explain what and why this is happening, giving the problem a meaning which is so important in a condition that is troubling and causing great suffering.

CRPS in the foot and leg causes great difficulty in walking and standing in many cases. If the tissues are stiffened and the control of movement is poor, the ability to walk normally can be severely limited. Add the pain to this scenario and it becomes incredibly disabling at times as the sufferer simply cannot undertake normal activities. In CRPS in the upper limb it is writing, computer use, dressing, holding tools and self-care that are challenged.

Similar to any painful state, determining the pain mechanism(s) is important in deciding where to focus the treatment. Often there can be co-existing mechanisms such as inflammatory pain and neuropathic pain underpinned by different processes and manifesting in different ways. Neuropathic pain is often sharp, lancing, shooting and accompanied by a loss of sensation in the same area that can be confounding until you understand how it works. Inflammatory pain can be provoked by movement and touch with the mechanism being excited sensory nerves (nociceptors) as a result of the release of inflammatory molecules. Nerves themselves can release such chemicals into the tissues (neurogenic inflammation) and thereby keep the process going. There are many other aspects to the pain and the drivers and influences.

As well as elucidating the pain mechanisms, identifying the influences is also very important. This can include stress, fatigue, emotional state, past experience, culture, beliefs in addition to lifestyle factors and general health. Personally I look for risk factors for chronicity with all new assessments so that these can be fealty with swiftly. When a condition has been in existence for a longer period, adapting this to understand behaviours, choices and other factors that could be prolonging the problem is important.

Modern treatment of pain including CRPS should be within a biopsychosocial framework. That means looking at the biological mechanisms, psychology and social factors that are all part of the pain experience and mould the individual perception. In many cases the sufferer needs input from physiotherapy, pain medicine and psychology. Initially educating the patient to develop understanding, reduce fear of the pain and movement and enable effective coping and self-care is key. Desensitising the body with a range of techniques that blend the physical with the cognitive through the application of various stimuli is useful. This could be a paint brush or cotton wool for example. Tactile discrimination and two point discrimination are normal sensory functions that can be altered and according to recent studies are likely to need training. The graded motor imagery programme is part of the treatment, targeting brain changes that can occur. The three stages are laterality, imagined movement and mirror therapy. This is a newer intervention and is demonstrating good results in CRPS and with other nasty pains. The self-care aspects are fundamental. Teaching the patient to manage their activities and to develop consistency through their day is key. Sometimes activities are overdone and there is a trade off. For example standing at a party, but you really want to go and afterwards you know it will hurt but accept that this will be the case. Good flare-up management skills can play a huge role during these times. A further group of interventions I call perceptual exercises. Due to the plastic changes in the sensory and motor cortices, the sense of self, body and movement can feel different in many ways. Working with this through the use of imagery, mindfulness, awareness and other strategies can really help to get back in touch with the body alongside the other techniques. Finally, motor control exercise to normalise movement is very important but to be done at the right time in the right way.

The context of the treatment can affect the success of the strategy. Timing, environment, understanding and belief must all be considered when designing a programme. Newer ideas and research about neuroimmune responses to exercise, movement and thoughts suggest that we need to be mindful of these factors. This is the modern way of looking at the individual, their pain and circumstances to offer practical and effective strategies in improving outcomes and quality of life.

Subsequent blogs will look at the other symptoms, why and how they manifest and the effects of stress upon the body.