Antidromic impulses constrained by Physics

[bernard]

The sensitive nervous system CHAPTER 3 page 55

While the pro-inflammatory contributors to the inflammatory soup arise from blood and the damaged tissues, the nervous system will also contribute. A closer look at the glandular C fibres is warranted.

THE GLANDULAR C FIBRES AND INFLAMMATION

The way C fibres work demands our attention. There are more than double the number of C fibres compared to A fibres
(Hulsebosch and Coggeshall 1981), four times as many according to Ochoa and Mair (1969). C fibres are unmyelinated and impulses travel at about 1% of the speed of A fibres. While they may not serve to signal the sharp pricking pains characteristic of A delta fibre stimulation, they will signal slower, less response demanding pains - sunburn sensations for example (Ochoa and Torebjork 1983; Raja et al. 1999). However, they also have an efferent, trophic function and could well be considered as glands of the peripheral nervous system (eg. Sann and Pierau 1998). C fibres contain neurotransmitters and neuromodulators such as excitatory amino acids, substance P (SP) and Calcitonin Gene Related Peptide (CGRP). These chemicals can be released into the dorsal horn but they can also be released into the target tissues. SP and CGRP are vasoactive peptides. They will make the cells of capillaries flatter, thus the capillaries become larger and leakier, causing plasma extravasation and thus swelling. The process is called neurogenic inflammation. This is a sterile and usually useful inflammatory process. Overall, it encourages healing (Kruger 1996) and beneficial immune system responses including the migration of leucocytes to the injury site (Nilsson et al. 1985). The process could evoke or increase vasodilation and pain as SP will make mast cells degranulate, releasing histamine or serotonin (Hagermark et al. 1978; Ebertz et al. 1987) and encouraging pro-inflammatory immune activity. It all makes the inflammatory soup a very sensitising soup for nerve endings.

The stimulus for the release of peptides into the target tissues is an antidromic impulse, which is an impulse that travels from proximal to distal in a C fibre (ie. the "wrong way"). An impulse which travels from distal to proximal in a C fibre is referred to as an orthodromic impulse (Fig. 3.6). This makes a neurone rather busy. The mechanisms for how it happens are not known, but the antidromic impulses somehow "fit" between the orthodromic impulses. Antidromic impulses can arise from injury along the nerve, the nerve terminals, or the dorsal root ganglion (Ehahl and Ladd 1976; Wall and Devor 1983; Daemen et al. 1998). Perhaps oscillating membrane potentials (Amir et al. 1999), short of spike, may maintain inflammation via antidromic mechanisms. In addition, antidromic impulses can also arise from the spinal cord, where they are known as dorsal root reflexes (Sluka et al. 1995) (Fig. 3.6). Although C fibres are a focus here, antidromic impulses also occur in A delta fibres (Kolston and Lisney 1993). Spinal cord evoked antidromic impulses are of interest suggesting that central inhibitory influences may mediate peripheral inflammation.

Looking at this passage of the book, I can't accept antidromic impulses in the areas evoked! It is against the principles of Physics?

Have you already some comments?

(More to come...)

[Alain]

Bernard:
We do it all the time when assessing conduction velocity in sensory nerves. So, strictly speaking, the physics do not get int the way. What antidromic conduction needs to happen is a source for the depolarization of the axon. That, Butler states, is not well understood. Could be a dendritic sprout from another nerve cell, volume conduction, ephaptic transmission, chemical irritation, etc.
See any good text on electrodiagnostic medicine.
Alain

[bernard]

Welcome on Somasimple, Alain.

I can't accept antidromic impulses in the areas evoked

I must actually reject the electrodiagnostic medicine since we know that neuron use ionic transmission and functioning.
Electricity is used as a convenient tool to explore neurons.

Of course antidromic impulses can be electrically created. they will go until a limit that was created by shaping and laws of physics. It is not because we could create in laboratories that in vivo, we find the same human existence of such thing.

I'm a bit surprised that a physical therapist reject Physics laws there?
Electricity is physics, Ions too, celerity already...

I will explain rationally my point of view. :wink:

[bernard]

Hello Somasimplers,

I put below the original references cited in the paper.
I boldlined some interesting words for my scientific demonstration.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1028017

Local oedema and general excitation of cutaneous sensory receptors produced by electrical stimulation of the saphenous nerve in the rat.
NO ABSTRACT AVAILABLE!!!
Chahl LA, Ladd RJ.

PMID: 1028017 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6664680

Pain. 1983 Dec;17(4):321-39.

Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats.

Wall PD, Devor M.

Single units were recorded in dorsal roots or in the sciatic nerve of anaesthetised rats. It was shown by making sections, by stimulation and by collision that some ongoing nerve impulses were originating from the dorsal root ganglia and not from the central or peripheral ends of the axons. In a sample of 2731 intact or acutely sectioned myelinated sensory fibres, 4.75% +/- 3.7% contained impulses generated within the dorsal root ganglia. In 2555 axons sectioned in the periphery 2-109 days before, this percentage rose to 8.6% +/- 4.8%. There was a considerable variation between animals; 0-14% in intact and acutely sectioned nerves and 1-21% in chronically sectioned nerves. The conduction velocity of the active fibres did not differ significantly from the conduction velocity of unselected fibres. The common pattern of ongoing activity from the ganglion was irregular and with a low frequency (about 4 Hz) in contrast to the pattern of impulses originating in a neuroma which usually have a higher frequency with regular intervals. Slight mechanical pressure on the dorsal root ganglion increased the frequency of impulses. Unmyelinated fibres were also found to contain impulses originating in the dorsal root ganglion. In intact or acutely sectioned unmyelinated axons, the percentage of active fibres 4.4% +/- 3.5% was approximately the same as in myelinated fibres but there were no signs of an increase following chronic section. Fine filament dissection of dorsal roots and of peripheral nerves and collision experiments showed that impulses originating in dorsal root ganglia were propagated both orthodromically into the root and antidromically into the peripheral nerve. It was also shown that the same axon could contain two different alternating sites of origin of nerve impulses: one in the neuroma or sensory ending and one in the ganglion. These observations suggest that the dorsal root ganglion with its ongoing activity and mechanical sensitivity could be a source of pain producing impulses and could particularly contribute to pain in those conditions of peripheral nerve damage where pain persists after peripheral anaesthesia or where vertebral manipulation is painful.

PMID: 6664680 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9471102


Neurol Res. 1998 Jan;20(1):41-5.

Neurogenic inflammation in an animal model of neuropathic pain.

Daemen MA, Kurvers HA, Kitslaar PJ, Slaaf DW, Bullens PH, Van den Wildenberg FA.

Department of General Surgery of the University Hospital Maastricht, The Netherlands.

Loose ligation of a rat sciatic nerve (chronic constriction injury (CCI) model) provokes signs and symptoms like those observed in reflex sympathetic dystrophy (RSD) patients. Primary afferent nociceptive C-fibers seem to be involved in an afferent orthodromic as well as in an efferent antidromic manner. In this study we hypothesize that consequent to development of antidromic impulses in C-nociceptive afferents, neuropeptides released from peripheral endings of these fibers, increase skin blood flow (SBF), vascular permeability, and tissue accumulation of polymorphonuclear leukocytes (PMNs). Collectively, these phenomena have been referred to as neurogenic inflammation. To investigate the presence of neurogenic inflammation in the CCI-model, we assessed skin blood flow (SBF) as well as the level of edema and accumulation of PMNs in muscle tissue obtained from the affected hindpaw. SBF was measured, by means of laser Doppler flowmetry, before ligation as well as at day 4 after ligation. At day 4, SBF measurements were performed before and after abolition of the capability of C-fibers to mediate a vasodilator response. To this end, capsaicin was applied perineurally. Increased vascular permeability was inferred from the level of edema of muscle tissue as determined by assessment of wet/dry weight ratios of muscle biopsies. PMN accumulation was investigated by enzymatic detection of myeloperoxidase (MPO) activity in muscle biopsies. Compared with preligation values, at day 4 SBF was increased more than twofold (p < 0.05). The latter response was annihilated by capsaicin application. Compared with sham operated controls, wet/dry ratios were higher in the ligated animals (1.104 vs. 1.068; p < 0.05). Likewise, when compared with sham operated controls, MPO activity was found to be increased in the ligated hindpaw (Optic Density 0.15 vs. 0.89; p < 0.001). In conclusion, the findings of this study indicate that loose ligation of a sciatic nerve induces an inflammatory response in the ipsilateral hindpaw, which most likely is mediated by release of neuropeptides from the peripheral endings of antidromically acting nociceptive C-fibres.

PMID: 9471102 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8246815

Microvasc Res. 1993 Sep;46(2):143-57.

A study of vasodilator responses evoked by antidromic stimulation of A delta afferent nerve fibers supplying normal and reinnervated rat skin.

Kolston J, Lisney SJ.

Department of Physiology, School of Medical Sciences, Bristol, United Kingdom.

Experiments have been carried out on anaesthetized rats to investigate some properties of the vasodilator responses evoked in skin by stimulation of small myelinated, A delta-fibers. Both normal and reinnervated skin in the saphenous nerve field were studied. In unoperated animals it was found that the magnitude and time course of the responses recorded from a particular patch of skin remain stable over a period of hours, but the responses varied in magnitude in different parts of the saphenous nerve territory. A delta-fiber evoked vasodilatation responses recorded from reinnervated skin were generally very similar to those seen in normal skin except that they tend to be smaller. These observations, taken together with previous findings, suggest that this ability of cutaneous A delta-fibers to influence the vasculature in the vicinity of their sensory endings has some physiological significance. Unfortunately, attempts to link these skin blood flow responses with activity of single, identified A delta-fiber units were not successful.

PMID: 8246815 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8985913

J Neurophysiol. 1996 Dec;76(6):4190-3. Related Articles, Links

Dorsal root reflexes in articular afferents occur bilaterally in a chronic model of arthritis in rats.

Rees H, Sluka KA, Lu Y, Westlund KN, Willis WD.

Department of Anatomy and Neurosciences, University of Texas Medical Branch at Galveston 77555-1069, USA.

1. Chronic arthritis was produced in rats by the injection of incomplete Freund's adjuvant into one knee joint. By 3-5 days later the rats had developed unilateral swelling of the injected knee and demonstrated bilateral hyperalgesia to radiant heat stimuli applied to the foot. 2. In the same rats anesthetized 3-5 days after the injection, dorsal root reflexes could be recorded bilaterally from the proximal ends of the cut medial articular nerves (MANs) of the knee joint. 3. The dorsal root reflexes consisted of large, medium-sized, and small action potentials evoked in response to phasic mechanical stimulation of the lateral aspect of the knee. The activity was greater in the MAN ipsilateral to the injection than in the contralateral MAN. 4. Local application of capsaicin on the side ipsilateral or contralateral to the arthritis dramatically reduced the dorsal root reflexes recorded from the contralateral MAN, indicating that these dorsal root reflexes depended on activity in fine afferent fibers containing capsaicin receptors, presumably C fibers. Local application of capsaicin on either side did not significantly change the dorsal root reflexes recorded from the ipsilateral MAN. These dorsal root reflexes were presumably conducted in afferent fibers that lacked capsaicin receptors, including A beta- and A delta-fibers.

PMID: 8985913 [PubMed - indexed for MEDLINE]

Any questions about my selections?

[bernard]

RULE 1
The speed of axon transmission is proportional to its diameter.

RULE 2
The Action Potential Amplitude of an axon is proportional to its diameter.

RULE 3
The Action Potential Amplitude of an axon is proportional to the number of located ions channels at its surface.


And now, Somasimplers, are you understanding why it is not physically possible to get an activation in the ending of C fibres?

[bernard]

The endings of a C-fibre is like a branch of a tree. And a branch of a tree has small/thin extremities which grow in the direction of the stem.
So the AP that is linked to the diameter of the fibre is obligatory small at these endings and grows for a while in the central direction, then it remains quite constant.

If it was possible to activate the fibre in the antidromic direction then the AP will decreases in the direction of periphery and will be quite null at the endings!
There is so no little chance to release some peptides in that way?:wink:

[bernard]

This formation like a branch brings some more advantages.

1/ an activation of a single branch is not sufficient to carry/fire an action potential.
2/ very good sensitivity.
3/ redundance.
4/ it needs almost several branchs to produce a valid AP.

5/ unfortunately, it has a default? Since a branch may fire lonely, it creates a noise actually known as chaotic.

[bernard]

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[bernard]

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[bernard]

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[bernard]

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It is quite impossible to measure an action potential in these areas since the diameter decreases, the AP, too. The level becomes so little that our actual apparatus are unable to track them.

[bernard]

Hi Somasimplers,

I was thinking since a long time about Schwann cells and myelin. I learnt that axons get a very good recovery of their myelin envelop when that one was injured. It is simply a fact that does not fit with the bare axolemna theory

More, we have all learnt that in case of myelinated axons, the presence of myelin is an indispensable necessity to carry APs. If myelin diseapears, AP is not transmitted.

Do you know that the myelin sheath is composed by at least 200 windings. It is a minimal value!

http://scienceweek.com/2004/sa040618-3.htm

http://staff.jccc.net/aalarabi/axonreg.html

http://www.weizmann.ac.il/Biological_Chemistry/scientist/Fainzilber/PerlsonJNB.pdf