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Diane
04-05-2008, 02:57 AM
This looks interesting: Static mechanical allodynia (SMA) is a paradoxical painful hypo-aesthesia: observations derived from neuropathic pain patients treated with somatosensory rehabilitation. (http://www.ncbi.nlm.nih.gov/pubmed/18344149?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

Spicher CJ, Mathis F, Degrange B, Freund P, Rouiller EM.

Somatosensory Rehabilitation Centre, Clinique Générale, Fribourg, Switzerland. reeducation.sensitive@cliniquegenerale.ch

The present study aimed at investigating the time span it takes to remove a static mechanical allodynia (SMA) in humans suffering from chronic peripheral neuropathic pain. Forty-three subjects were included in the study and, during somatosensory rehabilitation, their SMA territory was precisely mapped. They then underwent distant vibrotactile counter stimulation (DVCS) treatment. It was observed that, with DVCS, SMA disappeared in all cases, and was transformed into an underlying hypoaesthesia. It was found that the "tenderness to touch" symptom (which is SMA) was located in the same territory as the underlying hypoaesthesia, which was located on a part of the cutaneous territory of a partially damaged nerve. These results demonstrate that treating patients suffering from neuropathic pain with DVCS revealed a skin territory of denervation that was previously masked by SMA. Thus, SMA can be considered as a paradoxical painful hypoaesthesia. Furthermore, mapping SMA is a valuable source of information for our understanding of abnormal sensory processing in neuropathic pain patients. We conclude that the mapping of the zone of hypersensitivity on the skin in humans suffering from chronic peripheral neuropathic pain improves diagnosis. The mapping of the zone of hypersensitivity is a tool to presume which branch of the peripheral nerve is damaged. The location of the axonal lesions is at the periphery, while the mechanism of pain sensitization is probably central and referred peripherally to the skin by a painful hypoaesthesia.

And this: Paracrine-like excitation of low-threshold mechanoceptive C-fibers innervating rat hairy skin is mediated by substance P via NK-1 receptors. (http://www.ncbi.nlm.nih.gov/pubmed/18158108?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
Zhang SH, Sun QX, Seltzer Z, Cao DY, Wang HS, Chen Z, Zhao Y.

Faculty of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China. shzhang713@zju.edu.cn

We reported previously that C-fibers innervating rat skin can be excited by short trains of electrical shocks ('tetanus') applied to neighboring nerves. Since these nerves were disconnected from the CNS, the cross-talk is located peripherally. Here we tested if low-threshold mechanoceptive (LTM) C-fibers can be excited by this cross-talk and if this process is mediated by substance P (SP) via neurokinin-1 (NK-1) receptors. In urethane anesthetized rats we found that 80% (56/71) of LTM C-fibers, recorded in the lateral cutaneous branch of the dorsal ramus (CBDR) of T10 spinal nerve, were excited by a 10s, 20 Hz tetanus of the T9 CBDR. Compared to the spontaneous pre-tetanic firing frequency of 1.62+/-0.40 impulses/30s, the frequency significantly increased to 3.74+/-0.99, 3.17+/-0.69 and 2.92+/-0.63 impulses/30s, at 30, 60 and 90 s after the tetanus, respectively, and declined to the baseline frequency thereafter. When injected into their receptive fields, SP mimicked the tetanically induced increase of firing rate, whereas the NK-1 receptor antagonist WIN 51708 blocked the excitation in most fibers. The excitation was significantly diminished in adult rats that were neonatally treated with capsaicin, a treatment that destroys most SP-expressing afferent fibers. Thus, we conclude that peptidergic primary afferents are functionally linked with adjacent LTM C-fibers in a non-synaptic, paracrine-like signaling pathway via SP and NK-1 receptors, and perhaps also other agents as well. We propose that this cross-talk has evolved as a mechanism regulating the mechanoceptive characteristics of LTM C-fibers, presumably contributing to pain sensation elicited by tactile stimuli ('allodynia').

Diane
03-08-2008, 03:28 AM
The epidermis: a sensory tissue (http://www.ncbi.nlm.nih.gov/pubmed/18424369?dopt=AbstractPlus).

Jon Newman
03-08-2008, 03:47 AM
Hi Diane,

To your knowledge has this debate been resolved?

Exp Dermatol. (javascript:AL_get(this, 'jour', 'Exp Dermatol.');) 2004 Jan;13(1):2-4.http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.interscience.wiley.com-aboutus-images-wiley_interscience_150x34.gif (http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3046&itool=AbstractPlus-def&uid=15009109&db=pubmed&url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0906-6705&date=2004&volume=13&issue=1&spage=2) Links (javascript:PopUpMenu2_Set(Menu15009109);)
Connections between nerve endings and epidermal cells: are they synapses?

Chateau Y (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Chateau%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPane l.Pubmed_RVAbstractPlus), Misery L (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Misery%20L%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPane l.Pubmed_RVAbstractPlus).
Based on electron microscopy and confocal scanning microscopy, contacts between sensory axons and the cells of the epidermis have been described: with keratinocytes, Langerhans cells, melanocytes and Merkel cells. We would like to initiate a debate on this question: "Are neuro-epidermal connections synapses?" Anatomically, neuro-epidermal junctions can be considered as synapses in our opinion. If neuro-epidermal junctions are synapses, they probably belong to the family of en passant synapses, with nerve endings passing along epidermal cells and occasionally connecting to them. In conclusion, we suggest that neuro-epidermal junctions could be considered as true synapses, but this does not exclude non synaptic interactions.

Diane
03-08-2008, 04:05 AM
I think so. See Lumpkin (http://www.ncbi.nlm.nih.gov/pubmed/17314972).

Jon Newman
03-08-2008, 05:37 AM
File this (http://scienceblogs.com/neurophilosophy/2008/08/skin_cells_reprogrammed_to_form_neurons.php) under, "How cool is that?"

(Hat tip: Mo at Neurophilosophy (http://scienceblogs.com/neurophilosophy/))

Diane
03-08-2008, 06:21 AM
Yes. Very cool.
I saw this (http://www.somasimple.com/forums/showthread.php?t=4933) in Jan.

Diane
03-08-2008, 05:07 PM
Kevin at painonline wrote about this (http://www.painonline.com/2008/05/growing-new-neurons/). I'm trying to track down some of these articles but a couple aren't in the medline database yet, they are so new.
Here is one of them (http://www.pnas.org/content/105/15/5856.abstract?ck=nck), however. Go here (http://www.somasimple.com/forums/showthread.php?p=56549#post56549) to read it.
Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease
The long-term goal of nuclear transfer or alternative reprogramming approaches is to create patient-specific donor cells for transplantation therapy, avoiding immunorejection, a major complication in current transplantation medicine. It was recently shown that the four transcription factors Oct4, Sox2, Klf4, and c-Myc induce pluripotency in mouse fibroblasts. However, the therapeutic potential of induced pluripotent stem (iPS) cells for neural cell replacement strategies remained unexplored. Here, we show that iPS cells can be efficiently differentiated into neural precursor cells, giving rise to neuronal and glial cell types in culture. Upon transplantation into the fetal mouse brain, the cells migrate into various brain regions and differentiate into glia and neurons, including glutamatergic, GABAergic, and catecholaminergic subtypes. Electrophysiological recordings and morphological analysis demonstrated that the grafted neurons had mature neuronal activity and were functionally integrated in the host brain. Furthermore, iPS cells were induced to differentiate into dopamine neurons of midbrain character and were able to improve behavior in a rat model of Parkinson's disease upon transplantation into the adult brain. We minimized the risk of tumor formation from the grafted cells by separating contaminating pluripotent cells and committed neural cells using fluorescence-activated cell sorting. Our results demonstrate the therapeutic potential of directly reprogrammed fibroblasts for neuronal cell replacement in the animal model.

Diane
09-08-2008, 11:50 PM
Here is a link to the paper (http://www.somasimple.com/forums/showthread.php?t=5957) mentioned in post #1.