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Peripheral and central effects of nerve regeneration: Experimental and clinical studies
Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A nerve injury in the hand often results in profound abnmmalities in sensory perception despite careful alignment and microsurgical repair in order to facilitate accurate nerve regeneration. The present experimental and clinical studies were undertaken in an attempt to functionally evaluate peripheral and central effects of nerve regeneration.

In the experimental studies the rat foot was used as a model for the human hand. Three months after neurotomy and repair a flUlctional evaluation was performed of regenerated and misrouted polymodal nociceptor C-fibers and low-threshold mechanoreceptive axons by mechanical stimulation on the foot and electrical recordings proximal to the lesion and by Evans blue albumin extravasation.

It was found that 1) functional regeneration of misrouted axons related to polymodal nociceptive units and low-threshold mechanoreceptive units is more efficient in hairy skin of the rat foot whereas only misrouted polymodal nociceptor C-fibers recover function in glabrous skin, 2) following epineural suture and repair with a silicone tube after sciatic neurotomy there is similar effect on the regeneration of polymodal C-fibers after three months, and 3) functional regeneration of C-fibers is more successful in 3-month-old than in new-born rats.

In the clinical studies the functional effects of median nerve injury and regeneration were evaluated by two-point discrimination test, electroneurography, somatosensory evoked potentials and functional magnetic resonance imaging (IMRI). A method oftMRI during tactile stimulation was developed, and the normal cortical activation during stimulation was studied in 12 healthy volunteers.

The effects of nerve injury were studied in 6 injured adult men 15-55 months after median nerve injury and repair. It was found that 1) the 2-point discrimination was > 15 mm, 2) the nerve conduction velocity and signal amplitude were decreased in the severed nerve segment, but the cortical evoked response was normal at nerve stimulation proximal to the lesion, 3) tactile stimulation of the glabrous skin of the hand in healthy volunteers caused bilateral cortical activation (fMRI) in the primary somatosensory cortex, 4) a loss of sensory discrimination in the hand after median nerve injury was associated with a normal or even elevated activation (fMRI) in the somatosensory cortex during tactile stimulation of the digit IT-m.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2000. , 35 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 617
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-28041Local ID: 12802ISBN: 91-7219-574-6 (print)OAI: oai:DiVA.org:liu-28041DiVA: diva2:248592
Public defence
2000-03-03, Berzeliussalen, Universitetssjukhuset, Linköping, 09:15 (Swedish)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-03Bibliographically approved
List of papers
1. Functional evaluation of regenerated and misrouted axons to glabrous and hairy skin of the rat hind foot after sciatic neurotomy and suture
Open this publication in new window or tab >>Functional evaluation of regenerated and misrouted axons to glabrous and hairy skin of the rat hind foot after sciatic neurotomy and suture
1995 (English)In: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 132, no 1, 99-104 p.Article in journal (Refereed) Published
Abstract [en]

The function of misrouted regenerated polymodal nociceptor C-fibers and low-threshold mechanoreceptive axons in the lateral plantar nerve (LPN) and in the foot branch of the superficial peroneal nerve (fSPN) was evaluated 3 months after unilateral sciatic neurotomy and suture. Two weeks before evaluation the tibial fascicle (or the peroneal fascicle) above the neurotomy was cut and tied off. In this way only functional regeneration of misrouted axons was tested in the LPN (or the fSPN). In regenerated animals the glabrous skin area had no functional fSPN-related low-threshold mechanoreceptive axons. However, the hairy fSPN skin area showed function of misrouted LPN-related low-threshold mechanoreceptive axons. In both the glabrous skin domain innervated by the LPN and the hairy skin area supplied by the fSPN, functional regeneration of misrouted polymodal nociceptor C-fibers was found. We conclude that functional regeneration of misrouted axons related to polymodal nociceptive units and low-threshold mechanoreceptive units is more efficient in hairy skin of the rat foot whereas only misrouted polymodal nociceptor C-fibers recover function in glabrous skin.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79479 (URN)10.1016/0014-4886(95)90063-2 (DOI)
Available from: 2012-08-03 Created: 2012-08-03 Last updated: 2017-12-07Bibliographically approved
2. Functional Regeneration of C-Fibries Inside a Silicone Tube After Sciatic Neurotomy in Rats
Open this publication in new window or tab >>Functional Regeneration of C-Fibries Inside a Silicone Tube After Sciatic Neurotomy in Rats
1997 (English)In: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 31, no 1, 7-11 p.Article in journal (Refereed) Published
Abstract [en]

Peripheral nerve lesions are often complicated by difficulties in approximating the nerve tumps without tension. The aim of the present study was to evaluate C-fïbre function after nerve regeneration in rats in which the nerve had been lengthened by leaving a 5 mm gap inside a silicone tube (n = 5). The outcome was compared with nerve regeneration after epineural end-to-end suture (n = 5). The innervated skin territory was defined by Evans blue extravasation after antidromic nerve stimulation. Five rats acted as controls. After three months, there was similar functional reinnervation in both experimental groups, which indicates that silicone tubes may reduce tension over a nerve repair with no adverse effects.

Keyword
rat, neurotomy, silicone tube, defect, epineural suture, nociceptors
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79481 (URN)10.3109/02844319709010499 (DOI)
Available from: 2012-08-03 Created: 2012-08-03 Last updated: 2017-12-07Bibliographically approved
3. Inferior functional sensory regeneration after suture of sciatic neurotomy in newborns compared with mature rats
Open this publication in new window or tab >>Inferior functional sensory regeneration after suture of sciatic neurotomy in newborns compared with mature rats
1996 (English)In: Microsurgery, ISSN 0738-1085, E-ISSN 1098-2752, Vol. 17, no 5, 268-271 p.Article in journal (Refereed) Published
Abstract [en]

It is generally believed that nerve injuries in children regenerate better than those which occur in adults. However, there are no functional experimental studies that support this belief. This study evaluates the functional regeneration of polymodal C-fibres after nerve regeneration in newborn and mature rats 3 months after unilateral sciatic nerve neurotomy and suture. The distribution of polymodal C-fibres was tested by measuring the Evans blue-stained area in the skin after antidromic nerve stimulation. In the newborn group of regenerated animals showed that functional C-fibres were present in a significantly (P<0.05) smaller area than found in the adult group. We conclude that the functional regeneration of C-fibres is superior in mature rats compared with newborns, 3 months after regeneration.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79482 (URN)10.1002/(SICI)1098-2752(1996)17:5<268::AID-MICR6>3.0.CO;2-F (DOI)
Available from: 2012-08-03 Created: 2012-08-03 Last updated: 2017-12-07Bibliographically approved
4. Tactile stimulation of the hand causes bilateral cortical activation: A functional magnetic resonance study in humans
Open this publication in new window or tab >>Tactile stimulation of the hand causes bilateral cortical activation: A functional magnetic resonance study in humans
1999 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 271, no 1, 29-32 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of the present study was to assess the somatotopy of the cortical sensory representation of the fingers using a natural tactile stimulation of the glabrous skin. Multislice echoplanar imaging techniques were utilized to investigate blood oxygen level dependent (BOLD) signal changes as a measure of cortical activation. Repetitive sensory stimulation of the glabrous skin of digit II–III and digit IV–V resulted in a multifocal signal increase in a restricted area near the central sulcus in the contralateral hemisphere with a considerable overlap between the activated areas of digit II–III and digit IV–V. In addition, in all subjects tactile stimulation resulted in ipsilateral signal increase near the central sulcus, which was 15–22% of the contralateral effect. Stimulation of digit II–III caused significantly (P<0.05) more activated voxels than digit IV–V in the contralateral hemisphere for both hands and for the left hand in the ipsilateral hemisphere. These findings suggest an ipsilateral activation of the primary somatosensory cortex during a natural tactile stimulation of the digits in humans.

Keyword
Human, Ipsilateral, Functional magnetic resonance imaging, Sensory, Somatosensory, Tactile, Glabrous, Digits
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25067 (URN)10.1016/S0304-3940(99)00508-X (DOI)9497 (Local ID)9497 (Archive number)9497 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
5. Loss of sensory discrimination after median nerve injury does not decrease activation in the primary somatosensory cortex in fMRI
Open this publication in new window or tab >>Loss of sensory discrimination after median nerve injury does not decrease activation in the primary somatosensory cortex in fMRI
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The aim of this study was to assess functional effects of median nerve injnry and regeneration on the primary somatosensory cortex in adults. Activation in the somatosensory cortex was studied in 6 injured adult men and 12 healthy volunteers with functional magnetic resonance imaging (fMRI) and somatosensory evoked potentials. Examination 15 to 55 months (mean 38 ± 18) after a total transection of the median nerve at the wrist repaired with epineural suture showed a persistent loss of two point discrimination in digit II-III and a decrease in sensory nerve conduction velocity (-29 %) and amplitude (-84 %) in the median nerve segment at the wrist. The cortical somatosensory potential evoked by electrical nerve stimulation proximal to the lesion was normal in latency and amplitude. fMRl performed during tactile stimulation of dig II-III (distal to the lesion) resulted in all patients in activation near the contralateral central sulcus (n=4, two patients and one control were excluded because of movement artifacts). The activated area was increased by 48 %relative to stimulation of the unaffected hand (p<0.05) but not significantly different from controls. It is concluded that a loss of sensory discrimination in the hand following median nerve injury is associated with a normal or even elevated activation in the somatosensory cortex as measured with fMRI during tactile stimulation.

Keyword
functional magnetic resonance imaging, nerve injury, plasticity, regeneration, somatosensory
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79483 (URN)
Available from: 2012-08-03 Created: 2012-08-03 Last updated: 2012-08-03Bibliographically approved

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