Advertisement

Experimental Brain Research

, Volume 91, Issue 1, pp 61–72 | Cite as

Collateral reinnervation and expansive regenerative reinnervation by sensory axons into “foreign” denervated skin: an immunohistochemical study in the rat

  • Erik Kinnman
  • Håkan Aldskogius
  • Olle Johansson
  • Zsuzsanna Wiesenfeld-Hallin
Article

Summary

Immunohistochemistry has been used to study, the capacity of different types of sensory axons in the saphenous nerve to extend into denervated glabrous skin territory after a chronic sciatic nerve lesion. In this study, the extension of the intact or regenerating thin peptidergic and coarse saphenous nerve fibres in adult and neonatal rats was determined. Substance P (SP) and calcitonin gene-related peptide (CGRP) antibodies were used as markers for thin axons and neurofilament (NF) antibodies for coarse axons. In addition, S-100 protein (S-100) antibodies, which primarily stain Schwann cells associated with myelinated axons, as well as innervated lamellated cells of Meissner corpuscles, were used. After a chronic sciatic nerve lesion in adult rats, thin dermal and epidermal SP-immunoreactive (IR) and CGRP-IR saphenous nerve fibres were present in an area lateral to that normally innervated by the saphenous nerve in the foot sole. In neonatally lesioned animals, thin dermal and epidermal SP-IR and CGRP-IR, as well as coarse dermal NF-IR fibres and S-100-IR cells, all of which derived from the saphenous nerve, were found in the sciatic nerve territory. In addition, some dermal SP-IR and CGRP-IR fibres were transiently present in the lateral part of the foot sole. After chronic sciatic nerve lesion and a concomitant crush injury of the saphenous nerve in adults or neonatals, thin dermal and epidermal SP-IR and CGRP-IR fibres, as well as coarse dermal NF-IR fibres and S-100-IR cells, were found in the innervation area normally occupied by the sciatic nerve. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in adult rats, the SP-IR and CGRP-IR fibres, as well as the NF-IR fibres and S-100-IR cells were restricted to the medial part of this area. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in neonatal rats, a few thin dermal SP-IR and CGRP-IR fibres were found in the lateral part of the foot sole as well. The findings of the present study together with those of previous morphological studies indicate that intact thin axons from the saphenous nerve, including those exhibiting peptide immunoreactivity, but not coarse saphenous axons, are capable of extending into “foreign” denervated glabrous skin after chronic sciatic nerve injuries. In neonatally sciatic-nerve-injured animals, both groups of axons spread from the intact saphenous nerve into the sciatic nerve territory. This was also the case when the saphenous nerve had been crushed and allowed to regenerate in rats injured neonatally, or as adults. However, judging from previous physiological data, the regenerating axons do not develop into functional low-threshold mechanoreceptors.

Key words

Peripheral nerve injury Glabrous skin Sensory nerve endings Neuropeptide Rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Beuerman RW, Rózsa AJ (1984) Collateral sprouts are replaced by regenerating neurites in the wounded corneal epithelium. Neurosci Lett 44:99–104Google Scholar
  2. Bharali LAM, Lisney SJW (1989) Reinnervation of skin by poly modal nociceptors in rats. In: Hamann W and Iggo A (eds) Prog in Brain Res, vol 74. Elsevier, Amsterdam New York, pp 247–251Google Scholar
  3. Brain SD, Williams TJ (1985) Inflammatory oedema induced by synergism between calcitonin gene-related peptide (CGRP) and mediators of increased permeability. Br J Pharmacol 86:855–860Google Scholar
  4. Brenan A (1983) Collateral reinnervation of skin by C-fibers following nerve injury in the rat. Brain Res 385:152–155Google Scholar
  5. Brenan A (1986) Collateral reinnervation of skin by C-fibres following nerve injury in the rat. Brain Res 385:152–155Google Scholar
  6. Brenan A, Jones L, Owain NR (1988) The demonstration of the cutaneous distribution of saphenous nerve C-fibers using a plasma extravasation technique in the normal rat following nerve injury. J Anat 157:57–66Google Scholar
  7. Brodin E, Lindefors N, Dalsgaard C-J, Theodorsson-Norheim E, Rosell S (1986) Tachykinin multiplicity in rat central nervous system as studied using antisera raised against substance P and neurokinin A. Regul Pept 13:253–272Google Scholar
  8. Chiaia NL, Allen Z, Carlson E, MacDonald G, Rhoades RW (1988) Neonatal infraorbital nerve transection in rat results in peripheral trigeminal sprouting. J Comp Neurol 274:101–114Google Scholar
  9. Coons AH (1958) Fluorescent antibody methods. In: JF Danielli (eds) General cytochemical methods. Academic Press, New York, pp 399–422Google Scholar
  10. Dahl D, Bignami A (1977) Preparation of antisera to neurofilament protein from chicken brain and human sciatic nerve. J Comp Neurol 176:645–658Google Scholar
  11. Dahl D, Bignami A, Bich NT, Chi NH (1981) Immunohistochemical localization of the 150K neurofilament protein in the rat and the rabbit. J Comp Neurol 195:659–666Google Scholar
  12. Dalsgaard C-J, Jernbeck J, Stains W, Kjartansson J, Haegerstrand A, Hökfelt T, Brodin E, Cuello AC, Brown JC (1989) Calcitonin gene-related peptide-like immunoreactivity in nerve fibers in the human skin. Relation to fibers containing substance P-, somatostatin- and vasoactive intestinal polypeptide-like immunoreactivity. Histochemistry 91:35–38Google Scholar
  13. Devor M, Schonfield D, Seltzer Z, Wall PD (1979) Two modes of cutaneous reinnervation following peripheral nerve injury. J Comp Neurol 185:211–220Google Scholar
  14. Diamond J (1982) Modeling and competition in the nervous system: clues from the sensory innervation of skin. Curr Top Dev Biol 17:147–205Google Scholar
  15. Doucette R, Diamond J (1987) Normal and precocious sprouting of heat nociceptors in the skin of adult rats. J Comp Neurol 261:592–603Google Scholar
  16. Gamse R, Saria A (1985) Potentiation of tachykinin-induced plasma protein extravasation by calcitonin gene-related peptide. Eur J Pharmacol 114:61–66Google Scholar
  17. Haglid KG, Stavrou D (1973) Water-soluble and pentanol-extractable proteins in human brain normal tissue and human brain tumour, with special reference to S-100 protein. J Neurochem 20:1523–1532Google Scholar
  18. Koffert MJ, Greenberg RP, Wolskee PJ, Gracely RH, Wirdzek PR, Vinayakom K, Dubner R (1984) Abnormal and collateral innervations of sympathetic and peripheral sensory fields associated with a case of causalgia. Pain 20:1–12Google Scholar
  19. Horch K (1981) Absence of functional collateral sprouting of mechanoreceptor axons into denervated areas of mammalian skin. Exp Neurol 74:313–317Google Scholar
  20. Inbal R, Rousso M, Ashur H, Wall PD, Devor M (1987) Collateral sprouting in skin and sensory recovery after nerve injury in man. Pain 28:141–154Google Scholar
  21. Ishida-Yamamoto A, Senba E, Tohyama M (1989) Distribution and fine structure of calcitonin gene-related peptide-like immunoreactive nerve fibers in the rat skin. Brain Res 491:93–101Google Scholar
  22. Iwanaga T, Fujita T, Takahashi Y, Nakajima T (1982) Meissner's and pacinian corpuscles as studied by immunohistochemistry for S-100 protein, neuron-specific enolase and neurofilament protein. Neurosci Lett 31:117–121Google Scholar
  23. Jackson PC, Diamond J (1981) Regenerating axons reclaim sensory targets from collateral nerve sprouts. Science 214:926–928Google Scholar
  24. Jackson PC, Diamond J (1983) Failure of intact cutaneous mechanosensory axons to sprout functional collaterals in skin of adult rabbits. Brain Res 273:277–283Google Scholar
  25. Jackson PC, Diamond J (1984) Temporal and spatial constraints on the collateral sprouting of low-threshold mechanosensory nerves in the skin of rats. J Comp Neurol 226:336–345Google Scholar
  26. Jancsó G, Király E (1983) Cutaneous nerve regeneration in the rat. Reinnervation of denervated skin by regenerative but not collateral sprouting. Neurosci Lett 36:133–137Google Scholar
  27. Karlsson U, Schultz RL (1965) Fixation of the central nervous system for electron microscopy by aldehyde perfusion. I. Preservation with aldehyde perfusates versus direct perfusion with osmium tetroxide with special reference to membranes and the extracellular space. J Ultrastruct Res 12:160–186Google Scholar
  28. Kenins P (1981) Identification of the unmyelinated sensory nerves which evoke plasma extravasation in response to antidromic stimulation. Neurosci Lett 25:137–141Google Scholar
  29. Kenins P, Hurley JV, Bell C (1984) The role of substance P in the axon reflex in the rat. Br J Dermatol 111:551–559Google Scholar
  30. Kingery WS, Vallin JA (1989) The development of chronic mechanical hyperalgesia, autotomy and collateral sprouting following sciatic nerve section in rat. Pain 38:321–332Google Scholar
  31. Kinnman E, Aldskogius H (1986) Collateral sprouting of sensory axons in the glabrous skin of the hindpaw after chronic sciatic nerve lesion in adult and neonatal rats: a morphological study. Brain Res 377:73–82Google Scholar
  32. Klein BG, Renehan WE, Jacquin MF, Rhoades RW (1988) Anatomical consequences of neonatal infraorbital nerve transection upon the trigeminal ganglion and vibrissa follicle nerves in the adult rat. J Comp Neurol 268:469–488Google Scholar
  33. Kruger L, Sampogna SL, Rodin BE, Claque J, Brecha N, Yeh Y (1985) Thin-fiber cutaneous innervation and its intraepidermal contribution studied by labeling methods and neurotoxin treatment in rats. Somatosen Mot Res 4:335–356Google Scholar
  34. Kruger, L, Silverman JD, Mantyh PW, Sternini C, Brecha NC (1989) Peripheral patterns of calcitonin-gene related peptide general somatic sensory innervation: cutaneous and deep terminations. J Comp Neurol 280:291–302Google Scholar
  35. Lembeck F, Holzer P (1979) Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn Schmiedebergs Arch Pharmacol 310:175–183Google Scholar
  36. Leonard MH (1973) Return of skin sensation in children without repair of nerves. Clin Orthop 95:273–277Google Scholar
  37. Livingston WK (1947) Evidence of active invasion of denervated areas by sensory fibers from neighbouring nerves in man. J Neurosurg 4:140–145Google Scholar
  38. Lynn B, Carpenter SE (1982) Primary afferent units from the hairy skin of the rat hind limb. Brain Res 238:29–43Google Scholar
  39. McCarthy PW, Lawson SN (1989) Cell type and conduction velocity of rat primary sensory neurons with substance P-like immunoreactivity. Neuroscience 28:745–753Google Scholar
  40. McNeill DL, Westlund KN, Coggeshall RE (1989) Peptide immunoreactivity of unmyelinated primary afferent axons in rat lumbar dorsal roots. J Histochem Cytochem 37:1047–1052Google Scholar
  41. Mesulam MM (1978) Tetramethyl benzidine for horseradish peroxidase neurohistochemistry: a non-carcinogenic blue reaction-product with superior sensitivity for visualizing neural afferents and efferents. J Histochem Cytochem 26:106–117PubMedGoogle Scholar
  42. Mesulam MM, Hegarty E, Barbas H, Carson KA, Gower EC, Knapp AG, Moss MB, Mufson EJ (1980) Additional factors influencing sensitivity in the tetramethyl benzidine method for horseradish peroxidase neurohistochemistry. J Histochem Cytochem 28:1255–1259Google Scholar
  43. Metz GE, Judice RC, Finerty JC (1958) Occurrence of neurons in the sciatic nerves of albino rats. Anat Rec 130:197–205Google Scholar
  44. Neuberger TJ, Cornbrooks CJ (1989) Transient modulation of Schwann cell antigens after peripheral nerve transection and subsequent regeneration. J Neurocytol 18:695–710Google Scholar
  45. Nixon BJ, Doucette R, Jackson PC, Diamond J (1984) Impulse activity evokes precocious sprouting of nociceptive nerves into denervated skin. Somatosensory Res 2:97–126Google Scholar
  46. Owen DJ, Logan A, Robinson PP (1989) A role for nerve growth factor in collateral reinnervation from sensory nerves in the guinea pig. Brain Res 476:248–255Google Scholar
  47. Pertovaara A (1988) Collateral sprouting of nociceptive C-fibers after cut or capsaicin treatment of the sciatic nerve in adult rats. Neurosci Lett 90:248–253Google Scholar
  48. Pomeranz B, Mullen M, Markus H (1984) Effect of applied electrical fields on sprouting of intact saphenous nerve in adult rat. Brain Res 303:331–336Google Scholar
  49. Robinson PP (1981) Reinnervation of teeth, mucous membrane and skin following section of the inferior alveolar nerve in the cat. Brain Res 220:241–253Google Scholar
  50. Robinson PP (1983) Recession of sensory loss from the midline following trigeminal sensory root section: collateral sprouting from the normal side? Brain Res 259:177–180Google Scholar
  51. Robinson PP (1984) Evidence against a central stimulus for collateral reinnervation of oro-facial tissues in the cat. Brain Res 322:33–40Google Scholar
  52. Spreca A, Rambotti MG, Rendel M, Saccardi C, Aisa MC, Giamanco J, Donato R (1989) Immunocytochemical localization of S-100 protein in degenerating and regenerating rat sciatic nerves. J Histochem Cytochem 37:441–446Google Scholar
  53. Weddell G, Guttmann L, Guttmann E (1941) The local extension of nerve fibers into denervated areas of skin. J Neurol Psychiatry 4:206–225Google Scholar
  54. Wiesenfeld-Hallin Z (1988) Partially overlapping territories of nerves to hindlimb foot skin demonstrated by plasma extravasation to antidromic C-fiber stimulation in the rat. Neurosci Lett 84:261–265Google Scholar
  55. Wiesenfeld-Hallin Z, Kinnman E, Aldskogius H (1989) Expansion of innervation territory by afferents involved in plasma extravasation after nerve regeneration in adult and neonatal rats. Exp Brain Res 76:88–96Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Erik Kinnman
    • 1
  • Håkan Aldskogius
    • 1
  • Olle Johansson
    • 2
  • Zsuzsanna Wiesenfeld-Hallin
    • 3
  1. 1.Department of AnatomyKarolinska InstitutetStockholmSweden
  2. 2.Experimental Dermatology Unit, Department of Histology and NeurobiologyKarolinska InstitutetStockholmSweden
  3. 3.Department of Clinical Physiology and NeurophysiologyKarolinska InstitutetHuddingeSweden

Personalised recommendations