It is possible that people with spontaneous neuropathic pain may have multiple components of pain, including neuropathic and sensitization elements. By peripheal and central sensitization we mean a process of heightened pain perception derived from hypersensitivity to stimuli by sustained activation of peripheral nociceptors, eg, in the peripheral nerve. What is the step to spontaneous ongoing neuropathic pain? An other question is: Is spontaneous ongoing pain exclusive for neuropathic pain or

Dear Claude,

It is possible that people with spontaneous neuropathic pain may have multiple components of pain, including neuropathic and sensitization elements. By sensitization, I mean a process of heightened pain perception derived from hypersensitivity to stimuli by sustained activation of peripheral nociceptors, eg, in the peripheral nerve. Neuropathic pain may be characterized / accompanied by sensitization as well. Peripheral and central (segmentally related) pain pathways can become hyperexcitable in patients with neuropathic pain. Is the hyperexcitability exclusive for neuropathic pain as next step to spontaneous ongoing neuropathic pain? We see the same process in patients with, for instance, osteoarthritis, rheumatoid arthritis and chronic low back pain. This process can be summarized as follows:

• spontaneous activity
• decreased pain threshold
• recruitment of so-called silend nociceptors
• increased responsiveness to suprathreshold stimuli
• wind-up phenomenon at central level
• expansion of the excitatory fields (both peripheral as central)
• additional receptive fiels (both peripheral as central)
• increased stimulus-evoked release of neuropeptides
• dysregulation of sympathatic and motor reflexes / responses.

I hope, my contribution is a strating point to a valuable discussion on this topic.

Nijmegen, The Netherlands

October 16, 2014

Rob A.B. Oostendorp

Thank you for your Interesting question and answer: If there is  a certain contradiction concerning the common definition of a "spontaneous chronical neuropathic" pain, it will be helpfull to use the definition of  "spontaneous ongoing" neuropathic pain, indeed. 

Rheumatoid arthritis or chronic low back pain are  - simply defined -  in the typical case of neuropathy resp. radikulopathy, a so-called mixed pain, nociceptive and neuropathic and in my opinion as well a spontaneous ongoing and/or evoked pain.

Thank you for your interesting answers. In our discussion, I would like to exclude spontaneous ongoing pain WITH touch-evoked neuropathic pain. The neurophysiological mechanisms of this hypersensitivity are NOT similar.

Dear Claude,

Please have a look in a chapter we wrote with Wilfrid Jänig year ago (see attachment). There You will find our understanding how step by step the ectopic activity (including ongoing activity) develops. Half of this chapter is devoted to the ongoing activity after nerve injury. We disagree with Devor in the question of the origin of the ongoing activity. We believe, that spontaneous activity in injured afferent neurons may primarily originate in the periphery at the injury site and not in the dorsal root ganglion (DRG). The prove for this fact is in my manuscript  (2011) (https://www.researchgate.net/publication/49823070_Mechano-_and_thermosensitivity_of_injured_muscle_afferents). 

The transduction mechanisms of the ongoing activity of primary afferent neurons are related to several components, an important one being the voltage-sensitive sodium channels. It could well be, that the sensitization of the afferents - lowering the threshold of their thermal transduction mechanisms (for example of the TRPV1) is so profoundly that body tissue temperatures become a driving force of excitation of nociceptors - ongoing activity as well.  

Article Mechano- and thermosensitivity of injured muscle afferents

I think that the explanations are more complex. The neurophysiological mechanisms of spontaneous neuropathic pain follow i.e. traumatic injury. Such injury induice C neurofibre lesions AND A-bêta neurofibre lesions (Bouhassira & Attal, 2012). Your excellent  explanation about C neurofibre lesions DON'T exclude another explanation about A-bêta neurofibre lesions and the dysfunction of their Primary Somatosensory Neuron in the Dorsal Root Ganglion. In clinical practice, we observe partial tactile hypoaesthesia associated with spontaneous pain.

Della Casa, R., Mathis, F., Desfoux, N. & Spicher, C.J. (2010). Aesthesiology: A

useful knowledge to assess Neuropathic Pain Patients (NPP); About 2256 Axonal

Lesions of Cutaneous Branches. e-News Somatosens Rehab, 7(3), 128-137.

http://www.unifr.ch/neuro/rouiller/somesthesie/enews2010/e-News%20%207(3)#page=11.pdf

Claude,

we do not contradict each other. If the nerve is damaged, then all fibers - A- and C- afferent fibers, and efferent fibers are damaged. Both A- and C-afferent fibers after nerve injury develop ectopic discharges. The only difference between them is that C-fibers exhibit ectopic (ongoing) activity already in first hours, A-fibers  - 2-3 days after injury. I think A-betta fibers play enormous role in the neuropathic pain, specially deep somatic myelinated A-fibers, since apart from high rates of ongoing activity (15-30Hz) and lowered thresholds for mechanosensitity, they develop novel abnormal cold and heat-sensitivity after nerve damage. 

Dear Friends

I am interrested by neuropathic, apparently idiopathic pain, I encounter frequently in gastroenterology.

The main question is simple.

Why a normally painless stimulation is felt as painfull (allodynia) and, in the same way, why some pains are felt are more intense for thez same stimulation according to patients and locations.

Besides, suffering is not a simple consequence of pain and they depend (roughly) of different cortical régions, as vegetative reactions to pain.

First, with a,step-by-step, deductive approach, is to test by pressure and pinching the objective tenderness. As a matter of fact, as I noticed for coccyx  20y. ago, there is no strict parallelism between both (Maroy B. Spontaneous and evoked coccygeal pain in depression. Dis Colon Rectum 1988 ;31 :210-215).

It is, therefore, an abnormality in pain pathways i.e. isufficient filtration or excessive amplification. As there is no anatomical lesion, mechanism must be functionnal.

It is very interresting to notice the frequently homolateral phenomenom on face and body, suggesting non-decussing pathways. Disproportionate suffering and/or vegetative reaction suggest an excessive projection on anterior cingular gyrus and insula. Moreover, this pain is frequetly poorly sensitive to morphine and is in a large part, responsible for pain among evolved cancers.

With a synthetic, approach, I noticed  on the same ancient publication, association with classical signs of depression and cure by well used anti-depressants.

Since, I have developped the concept of depression being a pluri-systemic, functionnal, neurologic illness, with only possible psychic signs devoid of any causative role.

These concepts are detailed in my book in french "La dépression et son traitement : aspects méconnus" L'Harmattan Paris 20011 the English abstract being attached here.

Other consequences of this concept go far beyond pain problems.

I would be very happy to know anybody interrested by the present field

"I am interested by neuropathic, apparently idiopathic pain" SPLENDID this is my topic as well. We observe:

either spontaneous neuropathic pain with its partial tactile hypoaesthesia

or spontaneous neuropathic pain AND touch-evoked neuropathic pain (tactile allodynia).

In gastroenterology, the cutaneous branches that are involved in the neurologic somaesthetic process are:

Abdominal branch of Iliohypogastric nerve and/or Lateral branch of iliohypogastric nerve and/or Superior clunial nerve I

Abdominal branch of ilioinguinal nerve and/or anterior labial-scrotal nerve and/or Superior clunial nerve II

When the peripheral nerve is injured by various forms of etiology, the densities or functions of ion channels, particularly Nav, Kv channels, in the primary sensory neurons may be altered. One possible consequence is spontaneous subthreshold membrane potential oscillation, which usually triggers burst activities in the sensory neurons, particularly the myelinated Abeta neurons.

http://www.ncbi.nlm.nih.gov/pubmed/11844741

http://www.ncbi.nlm.nih.gov/pubmed/10899197

Dear Chang-Ning, Thank you very much indeed for these two papers of Devor's group. These studies were conducted on animals but the reading of these papers has been very informative.

In fact, the first problem is to understand why "neuropathic, spontaneous pain " occurs.

If the cause fails to be traeted, it is'nt surprising that it goes on.

In my experience, the main cause of neuropathic pain is depression, which is a neuro-biochemical illness with plurisystemic features.

Details in the joined english abstract of my book in frech, precising the neuro-functionnal mechanisms of the type of pain.