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An experimental model of peripheral nerve adhesion in rabbits

  • Yukio Abe
    Correspondence
    Corresponding author. Address: Department of Orthopaedic Surgery, Saiseikai Shimonoseki General Hospital, 3-4-1, Kifune-machi, Shimonoseki, Yamaguchi, 751-0823, Japan. Tel.: +81-832-31-5201; fax: +81-832-32-8209
    Affiliations
    Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
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  • Kazuteru Doi
    Affiliations
    Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
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  • Shinya Kawai
    Affiliations
    Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
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      Abstract

      We studied the effects of peripheral nerve adhesion in a rabbit sciatic nerve model. After nerve exposure, its adventitial layer was sutured with 8–0 nylon to the nerve bed, which had been cauterised to promote adhesion. Nerve kinematics, electrophysiology, blood flow and histology were assessed. Rabbits in which Fontana's bands were visible as normal through the epineurium, classified as a nonadhesion group (group I), lacked intraneural fibrosis. In this group, nerve conduction and nerve blood flow were well maintained. Rabbits in which Fontana's bands could not be seen were classified as the adhesion group (group II). This group was classified into two levels pathologically; thickening of epineurium and perineurium was observed but no endoneurial fibrosis (group IIa), and endoneurial fibrosis (Wallerian degeneration, myelin sheath thinning and fibrosis between nerve fibers) was noted (group IIb). Compound muscle action potentials (CMAP) were reduced in amplitude and blood flow was significantly decreased at adhesion sites in group IIb. In conclusion, adhesion of peripheral nerve to surrounding tissues results in fibrosis in the nerve that contributes to peripheral nerve dysfunction.

      Keywords

      A small but significant group of patients with entrapment neuropathy fails to improve following initial decompression surgery, and require a second operation. At reoperation, peripheral nerves often show lack of mobility resulting from adhesion of the nerve to surrounding scar tissues.
      • Leffert R.D.
      Anterior submuscular transposition of the ulnar nerves by the Learmonth technique.
      • Rogers M.R.
      • Bergfield T.G.
      • Aulicino P.L.
      The failed ulnar nerve transposition. Etiology and treatment.
      Adhesion is close by linked to the process of wound healing, but can lead to undesirable effect for nerves. Immobility of peripheral nerves caused by adhesion can result in serious problems such as focal, in excessive stretch, compression and impaired blood flow.
      • McLellan D.L.
      Longitudinal sliding of median nerve during hand movements: a contributory factor in entrapment neuropathy?.
      As underlying mechanisms, Lundborg et al. suggested that adhesion of peripheral nerves to surrounding tissues can lead to compressive edema within nerve bundles, fibrotic changes can interfere with blood flow to the nerve, and tethering can cause harmful stretch at distal sites along nerves during movement of the extremity.
      • Lundborg G.
      Mobility of peripheral nerves is characterised as sliding along their longitudinal axis during limb motion,
      • McLellan D.L.
      Longitudinal sliding of median nerve during hand movements: a contributory factor in entrapment neuropathy?.
      • Lundborg G.
      • Wilgis E.F.S.
      • Murphy R.
      The significance of longitudinal excursion in peripheral nerves.
      as modified by the visco-elastic behavior of individual nerve fibers, as shown in a variety of nerve-stretch experiments.
      • Beet J.A.
      • Groswald D.E.
      • Luttges M.W.
      Alterations in the mechanical properties of peripheral nerve following crush injury.
      • Kendall J.P.
      • Stokes I.A.F.
      • O'Hara J.P.
      • Dickson R.A.
      Tension and creep phenomena in peripheral nerve.
      • Kwan M.K.
      • Wall E.J.
      • Massie J.
      • Garfin S.R.
      Strain stress and stretch of peripheral nerve.
      In other words, mobility involves stretching and shortening of nerve fibers as well as the sliding of nerve bundles along nerve beds and within the epineurium and perineurium.
      • Millesi H.
      • Zoch G.
      • Rath T.
      The gliding apparatus of peripheral nerve and its clinical significance.
      Entrapment neuropathy has been thought to result from compression and secondary intraneural microenvironmental changes such as ischaemia, oedema and scarring.
      • Lundborg G.
      A variety of reports have described histologic abnormalities of affected peripheral nerves obtained postmortem
      • Neary D.
      • Ochoa J.
      • Gilliatt W.
      Sub-clinical entrapment neuropathy in man.
      as well as in animals.
      • Aguayo A.
      • Nair C.P.V.
      • Midgley R.
      Experimental progressive compression neuropathy in the rabbit.
      • Mackinnon S.E.
      • Dellon A.L.
      • Rydevik B.
      • Lundborg G.
      • Bogge U.
      Effects of graded compression on intraneural blood flow. An in vivo study on rabbit tibial nerve.
      • Spinner M.
      • Spencer P.S.
      Nerve compression lesions of the upper extremity.
      However, one should not neglect the consequences of adhesion of nerves to their beds or of bundle-to-bundle adhesion induced by compression.
      • Szabo R.M.
      • Bay B.K.
      • Sharkey N.A.
      • Gaut C.
      Median nerve displacement through the carpal canal.
      Although some investigators have studied the mobility of peripheral nerves, no in vivo animal model has been developed to investigate this issue.
      • Wilgis E.F.S.
      • Murphy R.
      The significance of longitudinal excursion in peripheral nerves.
      • Szabo R.M.
      • Bay B.K.
      • Sharkey N.A.
      • Gaut C.
      Median nerve displacement through the carpal canal.
      • Clarke E.
      • Beam J.G.
      The spiral nerve bands of Fontana.
      • McLellan D.L.
      • Swash M.
      Longitudinal sliding of the median nerve during movements of the upper limb.
      • Zoech G.
      • Reihsner R.
      • Beer R.
      • Millesi H.
      Stress and strain in peripheral nerves.
      In this study, we used rabbits, creating adhesion of the sciatic nerve to its bed to determine the consequences of peripheral nerve adhesion.

      1. Materials and methods

      Fifty male Japanese white rabbits (weight, 2.0–2.5 kg) were studied; these mature animals were selected to avoid developmental effects. Rabbits were housed in individual cages and given a normal diet and water. Animals were anaesthesized with pentobarbital sodium (40 mg/kg i.v.) followed by N2O/O2 and ethrane inhalation. In preliminary observations we established that arterial blood pressure remained stable during the experimental period using this anaesthetic method. Rabbits were placed right side down on an operating board. About 10 mm of the central portion of the left sciatic nerve was exposed by a posterolateral skin incision using aseptic technique, and freed of mesoneurial attachment. To produce adhesion, the nerve bed first was cauterised. Then the nerve was fixed in place by suturing its superficial (adventitial) layer to the cauterised bed with 8–0 nylon, taking care not to directly injure the nerve (N=40). To clarify the individual adhesion-promoting effects of nerve bed cauterisation and suturing the nerve adventitia, two other groups were studied. In one, the nerve bed was cauterised without suturing the nerve in place (N=5). In the other, sciatic nerves were sutured to noncauterised nerve beds (N=5). We compared adhesions formed in these two groups. Right and left sciatic nerves were exposed taking care not to injure blood vessels surrounding the nerves from the sciatic notch to the knee at 6, 14, 22, 30 or 38 weeks after the initial operation. We could not see obvious adhesion of the nerve at 3–4 weeks after initial operation; therefore, we needed at least 5–6 weeks to evaluate adhesion. The following evaluations were then made.

      1.1 Severity of nerve adhesion

      Scar tissue surrounding the nerve was removed under a dissecting microscope to expose the epineurium of the sciatic nerve. Under magnification the nerve adhesion was classified according to visibility of Fontana's bands, (an eponymically designated spiral pattern produced by nerve fiber undulation characteristic of peripheral nerve), through the epineurium.
      • Curtis R.M.
      • Eversmann W.W.
      Internal neurolysis as an adjunct to the treatment of the carpal tunnel syndrome.
      If Fontana's bands were clearly observed the nerve was classified as Group I, if bands were not clearly visible the adhesion was classified as Group II (Fig. 1) . In addition, pathological findings were recorded according to Sakurai's classification of neural fibrosis,
      • Sakurai M.
      • Miyasaka Y.
      Neural fibrosis and the effect of neurolysis.
      in which fibrosis progresses from extraneural to intraneural (Table 1) .
      Figure thumbnail gr1
      Figure 1Fontana's bands appear as spirals along the peripheral nerve. The bands can be clearly observed beneath the epineurium in normal peripheral nerve (A). Fontana's bands disappear in the nerve adhesion model (B).
      Table 1Sakurai's classification of neural fibrosis
      Grade
      1Normal
      2Extraneural type
      3Intraneural, epineural type
      4Intraneural, perineural type
      5Intraneural, endoneurial type
      6Dispersive type

      1.2 Nerve excursion during limb movement

      With the knee flexed and the sciatic nerve relaxed, we marked four points on the epineurium of right and left sciatic nerves with 4–0 nylon stay sutures: one point just distal to the sciatic notch, one just distal to the origin of the motor branch, one just distal to the origin of the tibial nerve, and one where the common peroneal nerve enters the tibialis anterior muscle. Nerve segments between marked points was designated a, b and c in proximal-to distal order (Fig. 2) . Segment lengths between marks were measured by digital calipers (coefficient of variation, ±0.01 cm). Nerve strain during limb motion were measured for each segment according to Lundborg's method.
      • Lundborg G.
      • Rydevik B.
      Effects of stretching the tibial nerve of the rabbit—a preliminary study of the intraneural circulation and the barrier function of the perineurium.
      Figure thumbnail gr2
      Figure 2Measurement of the elongation ratio of sciatic nerve.

      1.3 Electrophysiologic evaluation

      Motor nerve conduction velocity (MCV) and compound motor nerve action potentials (CMAP) were used to assess neural function. The CMAP was quantified by peak-to-peak amplitude. The nerve was bathed in a saline solution approximately 30 °C. A platinum needle recording electrode was placed in the tendon of the tibialis anterior muscle. A reference electrode was positioned in the hamstring muscle. A hand-held bipolar platinum needle electrode was used to apply supramaximal stimuli to the nerve just distal to the sciatic notch, using a square-wave pulse of 0.2 ms duration delivered by a stimulator. The nerve was also stimulated just proximal to its entrance into the tibialis anterior muscle. MCV and tibialis anterior CMAP recordings were collected, stored and analysed with an electrodiagnostic device (Counterpoint MK2, Dantec, Denmark). Measurement was performed in both limbs, and results concerning MCV and CMAP were expressed as the ratio of the affected side compared to the unaffected side.

      1.4 Nerve fascicle blood flow

      Fascicle blood flow in the sciatic nerve was measured from electrochemically generated hydrogen using a washout technique RBF-2 (Biomedical Science, Kanazawa, Japan). The perineurium enclosing nerve fascicle was fenestrated at the common peroneal nerve fascicle of the adhesion site, the corresponding point along the opposite sciatic nerve, and right and left common peroneal nerves, using an operating microscope. A BE-FS flexible unipolar electrode diameter 80 μm (Biomedical Science) was inserted through the fenestration for measurement of blood flow. A reference electrode was inserted into a subcutaneous pocket. During the hydrogen-generating phase of the measurement process, the voltage was set at 0.6 V with an applied current of 10 μA for 50 s. Since, we anticipated considerable variation between animal's we used each animal's contralateral side as a control. All results are expressed as ratios of measurements on the affected side to those obtained contralaterally.

      1.5 Histologic changes

      After completion of the above measurements, the nerve was excised and immersed in 3.0% phosphate-buffered glutaraldehyde, post-fixed in 1% osmium tetroxide, dehydrated through serially increasing concentrations of alcohol, and embedded in epoxy resin. For light microscopy, 1–3 μm-thick toluidine blue-stained axial sections were obtained. The degree of fibrosis of 2–3 sections of each specimen was carefully inspected and divided into Sakurai's histology classes.

      1.6 Statistical analysis

      Results are expressed as mean ±SD. Multiple analysis of variance (MANOVA) was used to assess relationships between length of nerve elongation, degree of adhesion and neurophysiologic and circulatory data. When the MANOVA showed significant differences, the elongation distance effect for the neurophysiologic and circulatory results was tested with Scheffe's post hoc test. In all statistical analyses, p<0.05 was considered to indicate statistical significance.

      2. Results

      2.1 Severity of adhesion

      We noted various degrees of adhesion surrounding the sciatic nerve (Fig. 3) . Severity of adhesion could be classified into three groups. Group I: Fontana's bands could be seen through the epineurium after resection of scar tissue surrounding the epineurium. This condition histologically corresponded to grade 2 and 3 in Sakurai's classification. Group IIa: bands were not clearly visible even after scar tissue removal, but fibrosis did not intrude into perineurium. This group corresponded to grade 4. Group IIb: intraneural endoneurial fibrosis was noted, corresponded to grade 5. In group I, extraneural scar formation was relatively mild compared to group II. No correspondence was noted between the period after initial operation and the severity of adhesion (Table 2) . As early as 6 weeks after initial operation, we could see group IIb fibrosis, while group I and IIa fibrosis were noted 38 weeks after the operation. Therefore, we ignored the duration and treated same degree of fibrosis as one group for the following evaluation. We were unable to identify factors affecting severity of adhesion in individual animals. In the two groups undergoing only cauterisation of the nerve bed or nerve suturing to a normal nerve bed, we did not see remarkable adhesion surrounding the nerve, either macro or microscopically.
      Figure thumbnail gr3
      Figure 3Severity of adhesion surrounding the sciatic nerve can be assessed. A is a specimen from group I, B is a specimen from group II, shows more severe adhesion.
      Table 2The relationship between the period after operation and number in groups I, IIa and IIb
      Postoperative duration (weeks)614223038
      Group
      I (N=16)63214
      IIa (N=14)13532
      IIb (N=10)12142

      2.2 Nerve kinematics

      Changes in the nerve strain during limb motion are presented in Table 3. In the normal sciatic nerve, the strain was the greatest near the knee joint, but did not exceed 10%. In the adhesion model, the strain was low at the adhesion site and in the proximal segment. Instead the distal segment of the nerve was overstretched, particularly in group II.
      Table 3Nerve strain (%) in each group by region during knee extension
      abc
      Normal (N=40)6.2±1.3 (%)5.5±2.19.2±1.4
      Group
      I (N=16)2.0±3.32.8±2.113.8±2.3
      IIa (N=14)1.2±1.00.8±1.517.0±2.4
      IIb (N=10)1.1±1.40.8±0.317.7±2.7

      2.3 Electrophysiologic changes

      MCV was 993±7.1% in group I, 96.1±7.8% in group IIa and 94.9±8.3% in group IIb (no significant decreases). On the other hand, CMAP amplitude was 94.6±14.2% in group I, 88.2±18.2% in group IIa, but only 69.8±113% in group IIb. No statistic abnormality was noted between group I and IIa, but a significant decrease was noted between group IIa and IIb (p<0.01); (Fig. 4) .
      Figure thumbnail gr4
      Figure 4Electrophysiologic differences in sciatic nerve between groups defined by adhesion severity.

      2.4 Nerve blood flow

      In group I, nerve blood flow comparable to that in the contralateral side was maintained at the adhesion site in the common peroneal nerve fascicle, independently of position of the limb. In group IIa, nerve blood flow was not decreased in the relaxed position, while it decreased in the stretched position (p<0.05). In group IIb, nerve blood flow was significantly decreased at the adhesion site in both the relaxed and the stretched position (p<0.001). Nerve blood flow at the common peroneal nerve was maintained in the relaxed position, but it was significantly decreased upon stretching (p<0.01) in group IIa and IIb (Table 4) .
      Table 4The change of nerve blood flow (affected side/unaffected side)
      Relaxed positionNerve extension position
      Adhesion site (common peroneal nerve fascicle)I89.5±15.5%NS87.0±20.9NS
      IIa80.6±12.8NS76.9±14.8(p<0.05)
      IIb60.3±15.1(p<0.001)58.5±15.7(p<0.001)
      Common peroneal nerveI92.5±17.8NSNS89.0±17.7NS
      IIa88.2±11.3NS77.1±18.1(p<0.01)
      IIb84.1±9.6NS76.9±12.5(p<0.01)

      2.5 Histologic changes

      Except for the formation around the epineurium, no remarkable changes were observed in group I (Fig. 5) . In group IIa, thickening of the epineurium and perineurium were noted together with interfascicular scar formation, especially surrounding interfascicular vessels, but no remarkable change was observed in endoneurial tissues (Fig. 6(A) and (B)). In group IIb, Wallerian degeneration of the nerve, thinning of the myelin sheath and fibrosis between nerve fibers also were found (Fig. 6(C) and (D)). These histologic changes were more pronounced in the common peroneal fascicle as it was nearest to the nerve bed. In both groups, no change was observed in the common peroneal nerve.
      Figure thumbnail gr5
      Figure 5Scar formation around the epineurium (black arrow) can be observed in group I (A, ×100). However, no changes are apparent in individual nerve fibers (B, ×200; toluidine blue).
      Figure thumbnail gr6
      Figure 6In group IIa and IIb, scar formation is seen in the interfascicular tissue around an intraneural vessel (A, ×200; hematoxylin and eosin (H and E)) and perineurium (B, ×200; H and E). Wallerian degeneration, thinning of the myelin sheath and fibrosis between nerve fibers also are observed in group IIb (C, ×200, D, ×400; toluidine blue).

      3. Discussion

      Early observations concerning peripheral nerve kinematics can be divided into studies of mechanical properties and studies of nerve excursion. In 1779, Felice Fontana described what appeared to be spiral bands surrounding peripheral nerve. These bands have been considered as representing nerve fiber undulation and can be seen readily through the epineurium is healthy nerve.
      • Clarke E.
      • Beam J.G.
      The spiral nerve bands of Fontana.
      • Haninec P.
      Undulating course of nerve fibers and bands of Fontana in peripheral nerves of the rat.
      • Sunderland S.
      The connective tissues of peripheral nerves.
      Regarding early studies of nerve excursion, McLellan et al. reported observations during limb motion of movement of a needle inserted through the skin into the trunk of the median nerve.
      • McLellan D.L.
      Longitudinal sliding of median nerve during hand movements: a contributory factor in entrapment neuropathy?.
      This group concluded that longitudinal sliding reduces local stretch that otherwise would occur during limb movement, as sliding allows an unstretched length of nerve to enter the extended region. As entrapment neuropathies are common in individuals, who use their limbs for repetitive tasks over prolonged periods, to-and-fro sliding through sites of potential entrapment could cause focal damage to a nerve.
      • McLellan D.L.
      Longitudinal sliding of median nerve during hand movements: a contributory factor in entrapment neuropathy?.
      • McLellan D.L.
      • Swash M.
      Longitudinal sliding of the median nerve during movements of the upper limb.
      The interface between the nerve trunk and surrounding tissues has been studied by Lang et al. who described an adventitia/surface that allowed ample gliding motion of the nerve trunk.
      • van Beek A.
      • Kleinert H.E.
      Practical microneurorraphy.
      Millesi also describes gliding layers within the nerve trunk allowing the fascicular bundles to slide in the epineurium.
      • Millesi H.
      • Zoch G.
      • Rath T.
      The gliding apparatus of peripheral nerve and its clinical significance.
      Excursion of peripheral nerve trunks thus appears to involve a complex array of multiple intra- and extraneural gliding surfaces.
      We prepared nerve adhesion models by suturing rabbit sciatic nerves to cauterised nerve beds. While no significant adhesions occurred in rabbits undergoing only nerve-bed cauterisation or only nerve suturing, predictable adhesion occurred in animals with both cauterisation and suturing. The severity of nerve adhesion was evaluated according to visibility of Fontana's bands and Sakurai's histologic classification. When Fontana's bands could be seen, less epineurial histologic change or functional impairment occurred. Loose connective tissue between the funiculus was preserved; this means intraneural gliding may be intact. Intrinsic vessels were normal, and intraneural blood flow was maintained. Absence of Fontana's bands suggested that fibrotic change had occurred around the perineurium (group IIa). In progression, Wallerian degeneration, thinning of the myelin sheath, fibrosis between nerve fibers, and reduced CMAP were observed (group IIb). The amplitude of the CMAP and the number and the averaged diameter of myelinated fibers are necessarily related,
      • Sadahiro T.
      • Fujita S.
      • Kamioka Y.
      An experimental study on internal neurolysis for entrapment neuropathy.
      and our results were in agreement. These changes resulted from the decrease of intraneural blood flow probably due to scar formation around the intrinsic vessels.
      The following theory may explain these findings. Extraneural adhesions apparently are followed by fibrosis overlying the epineurium and ultimately scar formation in the interfascicular connective tissue. Scar formation around the intraneural vessel in the interfascicular connective tissue decreases the neural blood flow and results in intrafascicular oedema, thinning of the myelin sheath and Wallerian degeneration. These changes are more severe in fascicles near the nerve bed. This suggests that fibrotic changes extend from the bed into the nerve. Furthermore, the epineurium and interfascicular connective tissue lose their function as a shock absorber, because of fibrosis, limiting tolerance to elongation.
      Dellon observed that Fontana's bands often could not be seen when the median nerve was inspected during carpal tunnel decompression, while the bands often returned following intraneural neurolysis.
      • Zachary L.S.
      • Dellon E.S.
      • Nicholas E.M.
      • Dellon A.L.
      The structural basis of Felice Fontana's spiral bands and their relationship to nerve injury.
      Such observations formed the basis for intraoperative assessment of the pathophysiologic state of the nerve. Based on our results, nerves in which Fontana's bands cannot be observed already have intraneural perineurial or endoneurial fibrosis. Disappearance of Fontana's bands appears to be a fairly reliable indicator of such fibrosis.
      When a nerve is compressed and adherent, distal limb motion produces longitudinal traction that compresses the nerve distal to the initial area of compression because of stretch-related narrowing,
      • Szabo R.M.
      Nerve compression syndromes.
      altering the internal architecture of the nerve at a distance from the initial compression. This partially explains why clinical symptoms extend beyond known areas of compression. Stretch-related exacerbation as described above may explain successful treatment of compressive lesions by long-term splinting. Holding the joint in one position limits longitudinal excursion. Such rest also decreases inflammation and swelling around the nerve. This may lead to resolution of the symptoms in some patients without a need for decompressive surgery.
      • Paternostro-Sluga T.
      • Keilani M.
      • Poach M.
      • Fialka-Moser V.
      Factors that influence the duration of splint wear in peripheral nerve lesions.
      We did not study splinting effects in our model because rabbit sciatic nerve has relatively few branches and is relatively unanchored. In our model adhesion was induced in the mid-portion of the nerve's length. Other parts of the nerve, especially the distal segment, would be able to compensate, limiting excessive stretching. Commonly compressed human peripheral nerves have many branches and course through narrow spaces such as the carpal tunnel, Frohse's arcade, and the cubital tunnel. As this anatomic situation limits compensatory mechanisms, such nerves are vulnerable to excessive stretch.
      Circulatory aspects of nerve stretching were investigated by Lundborg, who reported that complete intraneural ischemia was induced by rapid 15% stretch in the rabbit tibial nerve.
      • Lundborg G.
      • Rydevik B.
      Effects of stretching the tibial nerve of the rabbit—a preliminary study of the intraneural circulation and the barrier function of the perineurium.
      Ogata observed complete stasis of blood flow by rapid 15.6% strain in rabbit sciatic nerve.
      • Ogata K.
      • Naito M.
      Blood flow of peripheral nerve effects of dissection, stretching and compression.
      With more gradual elongation, Abe et al. found 40% elongation to be a critical point for rabbit sciatic nerve in terms of neurologic and circulatory compromise.
      • Abe Y.
      • Doi K.
      • Katoh Y.
      • Yamamoto H.
      • Kataoka H.
      • Kawai S.
      The limit of low speed peripheral nerve elongation; neurological and circulatory aspects.
      Although, we cannot directly compare our results with those of these rapid or slow elongations, the common peroneal nerve in our group IIb showed a strain of 17.7±2.7% and a blood flow decrease with knee extension to 76.9±12.5%. Repetitive limb motion may decrease blood flow at points distant from point nerve adhesion, causing ischemic nerve injury. Watanabe reported impairment of the blood-nerve barrier occurring with repetitive stretching of the nerve.
      • Watanabe M.
      • Yamaga M.
      • Kato T.
      • Lde J.
      • Kitamura T.
      • Takagi K.
      The implication of repeated versus continuous strain on nerve function in a rat forelimb model.
      Our results provide a basis for considering pathologic changes induced by nerve adhesion in clinical situations. Degenerative change or scarring of the nerve bed may occur due to trauma or surgery, repetitive motion, or systemic diseases like diabetes mellitus or chronic renal failure. This change disrupts gliding movement of nerve, and results in epineurial and interfascicular fibrosis and scar formation. Reduction of intraneural blood flow from such scarring surrounding intraneural vessels causes ischemic changes in intrafascicular tissue. In turn, these degenerative changes render nerves less elastic and more vulnerable to compression.
      Treatment of peripheral nerve adhesion remains controversial; extraneural and intraneural neurolysis have been performed.
      • Curtis R.M.
      • Eversmann W.W.
      Internal neurolysis as an adjunct to the treatment of the carpal tunnel syndrome.
      • Sakurai M.
      • Miyasaka Y.
      Neural fibrosis and the effect of neurolysis.
      When performing neurolysis on a nerve that is densely adherent to surrounding structures, one must ensure that longitudinal excursion will be restored postoperatively. If the local environment remains unaltered, adhesions will recur and clinical symptoms are likely to persist or return. Many techniques have been employed to alter the local environment, such as fat grafts, muscle flaps, wrapping with a vein, rerouting and vascularised nerve graft.
      • Mackinnon S.E.
      • Dellon A.L.
      • Doi K.
      • Tamaru K.
      • Sakai K.
      • Kuwata N.
      • Kurafuji Y.
      • Kawai S.
      A comparison of vascularized and conventional sural nerve grafts.
      • Varitimidis S.E.
      • Vardakas D.G.
      • Goebel F.
      • Sotereanos D.G.
      Treatment of recurrent compressive neuropathy of peripheral nerves in the upper extremity with an autologous vein insulator.
      • Wintsch K.
      • Helay P.
      Free flap of gliding tissue.
      The aim is to allow the scarred nerve to heal in a new environment free of adhesions.

      Acknowledgements

      No benefits in any form have been received from a commercial party related directly or indirectly to the subject of this article. This experiment was reviewed by the Committee of the Ethics on Animal Experiments in Yamaguchi University School of Medicine and carried out under the control of the Guideline for Animal Experiment in Yamaguchi University School of Medicine and The Law (No. 105) and Notification (No. 6) of the Government.

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