Innervation mapping of the hind paw of the rat using Evans Blue extravasation, Optical Surface Mapping and CASAM

BACKGROUND Although numerous studies investigate sensory regeneration and reinnervation of the hind paw of the rat after nerve damage, no comprehensive overview of its normal innervation is present in literature. The Evans Blue extravasation technique is a well-known technique to study patterns of skin innervation. This technique has been performed differently by various groups but was never used to study the entire skin innervation in rats' hind paw including all three branches of the sciatic nerve and the saphenous nerve in detail. NEW METHOD In this paper, we have used the Evans Blue extravasation technique to chart the skin areas innervated by the sural, peroneal, tibial and/or saphenous nerves, which together innervate the entire hind paw of the rat, and use a new technique to analyze the distribution, overlap and variability of the results. The technique is based on analysis of whole hind paws using Optical Surface Mapping (OSM) in combination with the Computer Assisted Surgical Anatomy Mapping (CASAM) technology. RESULTS While the plantar hind paw is mainly innervated by the tibial nerve, the dorsal hind paw is supplied by the sural, peroneal and the saphenous nerve. COMPARISON WITH EXISTING METHODS Although our results basically concur with the general nerve-specific innervation of the rat hind paw, they show considerable detail in their areas of overlap as well as in the amount of variability between animals. CONCLUSION These results will be invaluable to study and evaluate patterns of innervation and reinnervation of intact and damaged nerve fibers.

[1]  T. Yaksh,et al.  Quantitative assessment of tactile allodynia in the rat paw , 1994, Journal of Neuroscience Methods.

[2]  P. Eilers,et al.  An anatomical study of the ECRL and ECRB: feasibility of developing a preoperative test for evaluating the strength of the individual wrist extensors. , 2013, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[3]  J. McArthur,et al.  Cutaneous innervation in sensory neuropathies , 1995, Neurology.

[4]  F. Beaudry,et al.  Bilateral central pain sensitization in rats following a unilateral thalamic lesion may be treated with high doses of ketamine , 2013, BMC Veterinary Research.

[5]  W. Rossner,et al.  Quantitative Bestimmung der Permeabilitt der sogenannten Blut-Hirnschranke fr Evans-Blau (T1824) , 1966 .

[6]  G. Bennett,et al.  Sympathetic sprouting and changes in nociceptive sensory innervation in the glabrous skin of the rat hind paw following partial peripheral nerve injury , 2006, The Journal of comparative neurology.

[7]  Z. Wiesenfeld‐Hallin Partially overlapping territories of nerves to hindlimb foot skin demonstrated by plasma extravasation to antidromic C-fiber stimulation in the rat , 1988, Neuroscience Letters.

[8]  Fred Lembeck,et al.  Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation , 1979, Naunyn-Schmiedeberg's Archives of Pharmacology.

[9]  J. Szolcsányi,et al.  Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. , 1967, British journal of pharmacology and chemotherapy.

[10]  A. Oaklander,et al.  Unilateral nerve injury produces bilateral loss of distal innervation , 2004, Annals of neurology.

[11]  J. Dostrovsky,et al.  Evaluation of the time course of plasma extravasation in the skin by digital image analysis. , 2005, The journal of pain : official journal of the American Pain Society.

[12]  J. Hecksher-Sørensen,et al.  Optical Projection Tomography as a Tool for 3D Microscopy and Gene Expression Studies , 2002, Science.

[13]  B. Lynn,et al.  The Relationship between Cutaneous C Fibre Type and Antidromic Vasodilatation in the Rabbit and the Rat , 1997, The Journal of physiology.

[14]  B. Povlsen,et al.  Functional Projection of Regenerated Rat Sural Nerve Axons to the Hindpaw Skin after Sciatic Nerve Lesions , 1993, Experimental Neurology.

[15]  B. Povlsen,et al.  Functional regeneration of C-fibres inside a silicone tube after sciatic neurotomy in rats. , 1997, Scandinavian journal of plastic and reconstructive surgery and hand surgery.

[16]  G. Jancsó,et al.  A new technique for the direct demonstration of overlapping cutaneous innervation territories of peptidergic C-fibre afferents of rat hindlimb nerves , 1994, Journal of Neuroscience Methods.

[17]  A. Pertovaara Collateral sprouting of nociceptive C-fibers after cut or capsaicin treatment of the sciatic nerve in adult rats , 1988, Neuroscience Letters.

[18]  P. Eilers,et al.  The surgical anatomy of the small saphenous vein and adjacent nerves in relation to endovenous thermal ablation. , 2012, Journal of vascular surgery.

[19]  T. Guo,et al.  Colchicine treatment of the sciatic nerve reduces neurogenic extravasation, but does not affect nociceptive thresholds or collateral sprouting in neuropathic or normal rats , 1998, Pain.

[20]  A. Brenan Collateral reinnervation of skin by C-fibres following nerve injury in the rat , 1986, Brain Research.

[21]  A. Ribeiro-da-Silva,et al.  Delayed reinnervation by nonpeptidergic nociceptive afferents of the glabrous skin of the rat hindpaw in a neuropathic pain model , 2011, The Journal of comparative neurology.

[22]  Simona Ronchi Della Rocca,et al.  λ Δ -Models , 2004 .

[23]  J E Swett,et al.  The somatotopic organization of primary afferent terminals in the superficial laminae of the dorsal horn of the rat spinal cord , 1985, The Journal of comparative neurology.

[24]  V. P. Misra,et al.  A longitudinal study of sensory biomarkers of progression in patients with diabetic peripheral neuropathy using skin biopsies , 2012, Journal of Clinical Neuroscience.

[25]  J. Dostrovsky,et al.  Enhanced vascular permeability in rat skin induced by sensory nerve stimulation: Evaluation of the time course and appropriate stimulation parameters , 2008, Neuroscience.

[26]  A. Saria,et al.  Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues , 1983, Journal of Neuroscience Methods.

[27]  S. Hovius,et al.  Cold-induced vasodilatation in cold-intolerant rats after nerve injury. , 2013, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[28]  J. Vane,et al.  Optical Projection Tomography as a Tool for 3D Microscopy and Gene Expression Studies , 2002 .

[29]  T. Ruigrok,et al.  Re-innervation patterns by peptidergic Substance-P, non-peptidergic P2X3, and myelinated NF-200 nerve fibers in epidermis and dermis of rats with neuropathic pain , 2013, Experimental Neurology.

[30]  G. Weddell,et al.  Cutaneous sensibility. , 1962, Annual review of physiology.

[31]  P. Verhagen,et al.  Surgical anatomy of the 10th and 11th intercostal, and subcostal nerves: prevention of damage during lumbotomy. , 2011, The Journal of urology.

[32]  S. McMahon,et al.  Substance p in cutaneous primary sensory neurons—a comparison of models of nerve injury that allow varying degrees of regeneration , 1993, Neuroscience.

[33]  R. B. Carter Differentiating analgesic and non-analgesic drug activities on rat hot plate: effect of behavioral endpoint , 1991, Pain.

[34]  E. Perl,et al.  Relationship of substance P to afferent characteristics of dorsal root ganglion neurones in guinea‐pig , 1997, The Journal of physiology.

[35]  C. Woolf,et al.  Recovery of C-Fiber-Induced Extravasation Following Peripheral Nerve Injury in the Rat , 1998, Experimental Neurology.

[36]  A. Jamieson,et al.  The role of substance P and calcitonin gene-related peptide in neurogenic plasma extravasation and vasodilatation in the rat , 1989, Neuroscience.

[37]  G. Nicolini,et al.  Intraepidermal nerve fiber density in rat foot pad: neuropathologic–neurophysiologic correlation , 2005, Journal of the peripheral nervous system : JPNS.

[38]  J. Marty,et al.  Vascular properties of isoflurane: comparison between normal and cirrhotic rats. , 1998, British journal of anaesthesia.

[39]  E. Speel,et al.  Rapid Synthesis of Biotin-, Digoxigenin-, Trinitrophenyl-, and Fluorochrome-labeled Tyramides and Their Application for In Situ Hybridization Using CARD Amplification , 1998, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[40]  C. Dahlgren,et al.  A simple fluorescence technique to stain the plasma membrane of human neutrophils , 2004, Histochemistry.

[41]  J. R. Goff,et al.  The cold plate as a test of nociceptive behaviors: description and application to the study of chronic neuropathic and inflammatory pain models , 1998, Pain.

[42]  A. Brenan,et al.  The demonstration of the cutaneous distribution of saphenous nerve C-fibres using a plasma extravasation technique in the normal rat and following nerve injury. , 1988, Journal of anatomy.

[43]  M. Garwicz,et al.  Anatomical and physiological foundations of cerebellar information processing , 2005, Nature Reviews Neuroscience.

[44]  B. Povlsen,et al.  Functional Projection of Sensory Lateral Plantar and Superficial Peroneal Nerve Axons to Glabrous and Hairy Skin of the Rat Hindfoot after Sciatic Nerve Lesions , 1994, Experimental Neurology.

[45]  James Sharpe,et al.  Optical projection tomography as a new tool for studying embryo anatomy , 2003, Journal of anatomy.

[46]  T. Ruigrok,et al.  Spatiotemporal dynamics of re-innervation and hyperinnervation patterns by uninjured CGRP fibers in the rat foot sole epidermis after nerve injury , 2012, Molecular pain.

[47]  C. Woolf,et al.  Spared nerve injury: an animal model of persistent peripheral neuropathic pain , 2000, Pain.

[48]  Z. Wiesenfeld‐Hallin,et al.  Expansion of innervation territory by afferents involved in plasma extravasation after nerve regeneration in adult and neonatal rats , 2004, Experimental Brain Research.

[49]  W. Jänig,et al.  Small diameter myelinated afferents produce vasodilatation but not plasma extravasation in rat skin. , 1989, The Journal of physiology.

[50]  S. Jeng,et al.  Correlation between skin biopsy with quantification of intraepidermal nerve fiber and the severity of sciatic nerve traction injury in rats. , 2009, The Journal of trauma.