Stretch of mammalian nerve in vitro: Effect on compound action potentials

Abstract

Stretch of nerve has been reported to decrease the amplitude of the compound action potential (CAP) with a complete block appearing in approximately 30 minutes. But for the most part, those experiments were carried out in vivo, and it is generally accepted that the failure of responses was due to a closure of vessels supplying the nerve with a resulting ischemia and anoxia. These studies were undertaken to determine if stretch of nerve has effects that are independent of interference with its vascular supply. In the studies, lengths of rat sciatic and dog peroneal nerves were removed and placed in a chamber supplied with oxygen in which their CAPs were continuously elicited and recorded. This in vitro preparation obviated interference with the nerve's metabolism on stretching. We have previously shown that the form change termed 'beading,' appearing within 10 seconds and reversing as quickly on relaxation, can be elicited with tensions of only several grams. We wished to determine if stretch adequate to produce beading could alter CAPs with the same rapidity. Tensions below 2 g had little effect. On applying tensions of 10-100 g, levels well above those needed to bead the fibers, both increases and decreases of CAP amplitude were seen. The changes occurred within 10 seconds of stretch application, the time at which beading arises with stretch. Although the decreases of CAP amplitudes could be accounted for by beading, the degree of CAP change did not correspond to the amount of tension applied. We hypothesize that the constrictions in the beaded fibers increase axial resistivity and diminish local currents so as to block conduction. The lack of an increasing degree of decreased CAP amplitude with increases in tension is ascribed to the inhibition of elongation offered by the collagen fibrils present in nerve. Collagenase applied to nerves allowed a further increase in length, producing a 'hyperbeading,' showing much longer lengths of beading constrictions on stretch. This would further increase axial resistance and is taken to account for the greater decreases of CAP amplitudes seen following collagenase treatment. To account for those cases where increases of CAP amplitude were seen on stretch, we hypothesize that stretch can also cause an increase in the excitability of the nodes. The outcome of stretch in any given nerve would be the resultant of two opposing actions; beading of the internodes causes a decrease of local currents leading to block of CAPs, while an increased excitability of the nodes acts to augment the responses.

Stretch-induced nerve conduction deficits in guinea pig ex vivo nerve

“…Thus, there appears to be differences in the electrophysiology when either a creep or stress relaxation paradigm is used. The current experimental model does not explain the mechanistics of the mechanical injury but possibilities that have been proposed include transient changes in membrane ion channel conformation, a damaged membrane, myelin disruption or an increase in axial resistivity that diminishes ionic currents (Haftek, 1970;Galbraith et al, 1993;Ochs et al, 2000). We speculate from our compound membrane potential data that the membrane was not compromised, even at 20% stretch.…”

“…In vivo studies may therefore, have a component of damage associated with the hemodynamic response. With ex vivo preparations, mechanical injury can be isolated from the confounding ischemia (Ochs et al, 2000;Shi and Blight, 1996;Shi and Pryor, 2002).…”

“…It may be possible that the reorientation of yet undetermined internal elements during relaxation could ameliorate conduction deficit. An alternative hypothesis that has been proposed describes a state of increased membrane/nodal excitability initiated by stretch (Ochs et al, 2000;Tanelian and Markin, 1997). This explanation could lead to the increased CAP signals.…”

Investigating the mechanical shear-plane between core and sheath elements of peripheral nerves

“…Based on information from other connective tissues, these layers probably work in concert to provide peripheral nerves with their remarkable mechanical properties. In particular, they are able to withstand major changes in tensile load before conductive function is altered Ochs et al 2000). The overall tensile properties of nerves have been measured in many animal and human studies but little is known about the contribution made by each element within the nerve.…”

A device for the electrophysiological recording of peripheral nerves in response to stretch

“…Indeed during nerve elongation, there is constriction of the vasculature and decreased blood flow within nervous tissue (Lundborg and Rydevik, 1973;Jou et al, 2000). The subsequent ischemia is sometimes believed to be the primary culprit leading to functional deficit, although some suggest there may be an earlier mechanism ascribed to mechanical deformation Ochs et al, 2000;Driscoll et al, 2002). We also hold the view that prior to ischemic injury there is a mode of mechanical injury that is responsible for the observed conduction block.…”