Question of interest, indeed. Probably you find some actual papers looking for multimodal therapy of neuropathic pain, including central and peripheric causes, injury of brain and spinal cord as well as  of distal peripheric nervs like CRPS II.

Please see: Binder et al. Transient Receptor Po...atients PLosOne 6 (2011) e17387.pdf

Article Transient Receptor Potential Channel Polymorphisms Are Assoc...

Distinguishing central sensitization from peripheral pain is an interesting theoretical, diagnostic and clinical challenge.  See Marshall Devor's recent paper on phantom limb pain for a thought-provoking read (Pain. 2014 Aug 25. pii: S0304-3959(14)00377-7. doi: 10.1016/j.pain.2014.08.018. [Epub ahead of print]).

Despite the challenges of unpicking the mechanisms, one of the unique features of CRPS is the vasomotor and thermoregulatory changes seen with this syndrome.  Although there are no studies (yet) that comprehensively address the discriminative validity of skin temperature asymmetry measurements to distinguish CRPS from nerve injury or the inflammatory sequelae of trauma, several papers have  suggested skin temperature measures of the affected limb vs. contralateral limb and/or rewarming after cold stress may be useful clinical indicators (see Niehof et al, Anesth Analg 2008;106:270 –7; Niehof et al (2006)  Thermography imaging during static and controlled thermoregulation in complex regional pain syndrome type 1: diagnostic value and involvement of the central sympathetic system.  BioMedical Engineering OnLine, 5:30; Oerlemans et al. (1999). Objective and subjective assessments of temperature differences between the hands in reflex sympathetic dystrophy.  Clinical Rehabilitation, 13: 430–438.) 

While Niehof's 2007 paper did not find temperature differences to be a compelling diagnostic tool, he emphasized the testing took place in a resting state.  His previous work used thermoregulatory stress conditions to look for differences, and as a clinician and researcher, this is an area I am exploring as I see the potential both for diagnosis and clinical uptake.  This is a component of my thesis work (am currently enrolling patients in a study comparing persons with CRPS to persons after nerve injury or fracture), so I hope to have more evidence in about 18 months!

"Damage in Aβ neurofibres is peripheral, the mechanisms for pain sensitization are mostly centrally driven, with referral back to the peripheries where it is perceived as a paradoxical painful to touch hypo-aesthesia." (McCabe, 2009).

http://www.neuropain.ch/sites/default/files/e-news/e-news_61.pdf

and 95% of CRPS'patients are suffering of Damage in Aβ neurofibres

Evidence for supraspinal central mechanisms in CRPS derives from studies using neuroimaging techniques that Permit Exploration of changes in Information processing in the Brains of CRPS patients indicating that alterations of afferent Input lead to cortical and thalamic plasticity and reorganization of sensory representations in these patients. (for details see the papers of Maihöfner and colleagues: Neurology 2003; 61: 1707-1715, Neurology 2004; 63: 693-701, Pain 2005; 114: 93-103; Brain 2007; 130: 2671-2687, Der Schmerz 2010; 24: 137-145.

Injury-induced sensitization was described by Woolf et al. as an Archetyp model of central sensitization (Nature 1988; 306: 686-688). For the role of NMDA-receptors and long-term potentiation of synaptic efficacy  see Sandkühler (Mol. Pain 2007; 3: 9).

About injury-induced sensitization Clifford J Woolf wrote as well an excellent article in Neuron:

Hehn von, C, Baron, R. & Woolf, C.J. (2012). Deconstructing the Neuropathic Pain Phenotype to Reveal Neural Mechanisms. Neuron, 73, 638-352.

Dear colleagues,

Central sensitivity syndrome is a term first used by Yunus in 2000 to describe a group of overlapping conditions bound by a common pathophysiological mechanism of central sensitization. In number of cases, the medical diagnosis can provide the clinician with important information in relation to central sensitization. A body of literature is available linking medical diagnosis (e.g. CRPS type I, chronic low back pain, whiplash associated disorders) to central sensitization. Many medical diagnoses are associated but not uniformly characterizzed by central sensitization.

All the articles from a clinical point of view emphasize a histoy taking in detail, for instance according the SCEGS method (S = somatic; C = cognitive; E = emotional; G / B = gedrag (Dutch) / behaviour; S = Social). Listening to the story of patients will provide a number of clues that potentially point towards the presence of sensitization of the peripheral and central nervous system. Central sensitization (in contrast with peripheral sensitization) entails much more than generalized hypersensitivity to pain. It is characterized by an increased responsiveness to a variety of stimuli including mechanical pressure, chemical substances, cold and heat temperature, electrical stimuli, stress, emotions and mental load. The clinical picture is suggestive of a general intolerance to all kinds of stressors and hence a decreased tolerance load of the human body in general. It is therefore recommended to take a very detailled and structured history.

Based on my clinical experience and research in CRPS type I and different medical diagnoses associated with peripheral and central sensitization, and in application of pain neurophysiology in (manual) physiotherapy practice I know the question of Rosi Goldsmith is very complex and clinically very interesting. I hope to have given some insights  in the clinical appraoch of patients with sometimes medically  unexplained and unexplainable pain.

Nijmegen, The Netherlands

September 14, 2014

Rob Oostendorp.

Many thanks Rob for these informations. Marshall Devor proposed the very clear concept of "A-beta pain" to explain part of this touch-evoked pain (Devor, 2009). Devor M. Ectopic discharge in Aß afferents as a source of neuropathic pain. ExpBrain Res 2009;196:115-28.

Moreover, tactile allodynia is maintained by peripheral input (Devor and Tal, 2014).

Devor M and Tal M. Nerve resection for the treatment of chronic neuropathic pain Commentary on the Clinical Note by: Watson, C.P., Mackinnon, S., Dostrovsky J, Bennett, G., Farran P., Carlson, T. Nerve resection, crush and grafting relieves complex regional pain syndrome II (causalgia): a case report. PAIN® 2014;155(6):1053-4.

And finally,  the sensitized nociceptor hypothesis does not explain tactile allodynia. A significant body of evidence indicates that hypersensitivity to touch is signaled by low-threshold Aβtouch afferents, NOT sensitized nociceptors (Devor, 2013). 

Devor M. Neuropathic Pain: Pathophysiological Response of Nerves to Injury. Chapter 61. In SB McMahon, M Koltzenburg, I Tracey and D. C. Turk editors. Wall and Melzack’s Textbook of Pain, 6th ed. Philadelphia: Elsevier Saunders; 2013. pp. 861-888.

Fribourg (Switzerland)

only briefly (shortage of time today): 1. The defining sensory feature of CRPS is pressure hyperalgesia (far above any othr hyperalgesic change). 2. in the acute phase there is a prominent appearance of paradoxical heat sensation (mistaking the alternating presence of cold and warm objects as painfully hot). This vanishes completely in the chronic phase. There is a spread of sensory symptoms to the contralateral side. We have published to comprehensive papers on sensory alterations in CRPS, the latter one is the only one explicitly (causally) relating the development of pressure hyperalgesia to the motor disability (both open access on PLoS ONE). As you are a manual therapist this may offer a mechanistic explanation of manual therapy-related improvement.  Hope this helps,  best wishes, Walter

There is a group called body-in-mind organized by Lorimer Mosley, which also discusses interesting findings on CRPS. Recommend to look it up   http://www.bodyinmind.org/who-are-we/

and, last not least, I attached a marvellous recent review (one of the best reviews I have read on any topic) by Borchers and Gershwin

by the way: dynamic mechanical allodynia is primarily based on crosstalk of A-beta fibers into nociceptiv projection pathways at the spinal level !! Any other idea seems far-fetched to me. attached another review by melf and a colleagues, which may otherwise by hard to access

Dear Rosi and Claude, Dear all,

Thank you for your additional information on the fundamental insights into the origin and existence of CRPS type I in combination with central and peripheral sensitization. The learned lesson is that (manual) physical therapist must be familiar not only with the bio-psycho-social context of the health problems but also with modern insights into pain neuroscience which reconceptualization of pain centered. Reconceptualization of pain is not only important for the patient but also for the treating therapist. Therapeutic pain neuroscience education is one of the most promising treatments options for patients with CRPS type I prior to and continuing into active exercise therapy and multidisciplinary rehabilitaion programs.

Nijmegen, September 17, 2014

Rob Oostendorp

Dear Colleagues,

I cannot express in words how grateful I am for your answers. I have looked up all the references you suggested, and they have led me to others. You have clarified that my patient did not have CRPS, because in his symptom presentation and medical history he did not have the heat, the thermoregulatory changes. And you convinced me that I cannot cite CRPS research that shows benefit from contralateral inhibition, even though I have failed to find comparable CS research that speaks to my findings.

Much of the literature states that CS is both complex and underdiagnosed. As well, there is little research on manual therapy approaches. This leaves me struggling to create a reasonable hypothesis for what I stumbled upon that turned out to be successful: contralateral inhibitory (CI) movement and massage techniques for unilateral pain.

I found this successful for two other upper extremity, UE cases, but did not find it successful for LE severe chronic pain. Your answers made me look back through my LE cases, and I realized they also had heat, burning sensations along with allodynia and hypersensitivity to touch--indicators for CRPS. I now know my previous hypothesis of UE and LE differences to have been a blind alley. I had been looking at how sensory and motor neuron pathways are arranged in the dorsal horn of the spinal cord, for an understanding of CI effects. Still don't know if that is entirely irrelevant? But this discussion has also helped me understand the limitations of small sample case studies.

I admit that I am a bit over my head. I am motivated by compassion for the extreme suffering of people in so much pain, and their families, and the stunning reversal of it in this case. Your willingness to share your experiences and expertise has been invaluable. I will certainly reread the materials you suggested!

Thank you!

Differentiating central from peripheral pain seems to me often impossible because both is most frequently present, although it has been proven, that exclusive central pain can be elicited. The anatomical distribution of symptoms in fibromyalgia syndromes and in neuroinflammation may be explained on the one hand by the nerves and neuronal connectivity, but an intriguing idea according to my opinion is an own hypothesis from unexpected observations in severe depression and chronic pain syndrome treated with CSF filtration: pain and depression disappeared within days, before being chronic for long time (catamnesis of 15 years now in one case). This suggested that CSF itself is signaling. The CSF outflow pathways demonstrated a distribution all over brain and spinal nerves and therefore the appearance can involve the whole body (with only minor asymmetries) depending from CSF flow mechanisms (compare my recent short paper and the previous hypothesis), both needing much more scientific work.