By using immunohistochemistry and antibodies to a general nerve marker, protein gene product (PGP) 9.5, the overall innervation at the extensor carpi radialis brevis (ECRB) muscle origin was investigated in patients with tennis elbow and in healthy controls. The autonomic innervation was studied by using antibodies to neuropeptide Y (NPY), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP). The sensory innervation was visualized by using antibodies to substance P and calcitonin gene-related peptide. PGP 9.5 immunoreactions were detected in association with small blood vessels and arteries and within nerve bundles. There was, however, heterogeneity in the perivascular nerve fiber distribution since some blood vessels exhibited a high degree of PGP 9.5 innervation and some negligible or no such innervation at all. There was marked TH/NPY innervation in the walls of a subpopulation of the arteries, basically no VIP-containing nerves, and sensory innervation restricted to the small blood vessels. These observations show that the ECRB muscle origin is supplied with heterogeneously distributed sympathetic and sensory innervations and, furthermore, that there appears to be an imbalance between the vasoconstrictor and vasodilator innervations along the vascular tree in this region.

Keywords:
Muscle origin, human, Sympathetic innervation, Sensory innervation, Blood vessels, Tendon, Tennis elbow
1.
Ahmed, M., A. Bjurholm, A. Kreicberg, M. Schultzberg (1993) Sensory and autonomic innervation of the facet joint in the rat lumbar spine. Spine 18: 2121–2126.
2.
Anderson, R., I.L. Gibbins, J.L. Morris (1996) Non-noradrenergic sympathetic neurons project to extramuscular feed arteries and proximal intramuscular arteries of skeletal muscles in guinea-pig hindlimbs. J Auton Nerv Syst 61: 51–60.
3.
Arnalich, F., E. de Miguel, C. Perez-Ayala, M. Martinez, J.J, Vazquez, J. Gijon-Banos, A. Hernanz (1994) Neuropeptides and interleukin-6 in human joint inflammation. Relationship between intraarticular substance P and interleukin-6 concentrations. Neurosci Lett 170: 251–254.
4.
Aro, H. (1985) Effect of nerve injury on fracture healing. Callus formation studied in the rat. Acta Orthop Scand 56: 233–237.
5.
Ashton, I.K., B.A. Ashton, S.J. Gibson, J.M. Polak, D.C. Jaffray, S.M. Eisenstein (1992) Morphological basis for back pain: The demonstration of nerve fibers and neuropeptides in the lumbar facet joint capsule but not in ligamentum flavum. J Orthop Res 10: 72–78.
6.
Bjurholm, A., A. Kreicbergs, L. Terenius, M. Goldstein, M. Schultzberg (1988) Neuropeptide Y-, tyrosine hydroxylase- and vasoactive intestinal polypeptide-immunoreactive nerves in bone and surrounding tissues. J Auton Nerv Syst 25: 119–125.
7.
Brown, M.F., M.V.J. Hukkanen, I.D. McCarthy, D.R.M. Redfern, J.J. Batten, H.V. Crock, S.P.F. Hughes, J.M. Polak (1997) Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease. J Bone Joint Surg 79-B: 147–153.
8.
Bülbring E., J.H. Burn (1935) The sympathetic dilator fibres in the muscles of the cat and dog. J Physiol 83: 483–501.
9.
Chard, M.D., T.E. Cawston, G.P. Riley, G.A. Gresham, B.L. Hazleman (1994) Rotator cuff degeneration and lateral epicondylitis: A comparative histological study. Ann Rheum Dis 53: 30–34.
10.
Dehal, N.S., A. Kartseva, L.C. Weaver (1992) Comparisons of the locations and peptide content of postganglionic neurons innervating veins and arteries of the rat hindlimb. J Auton Nerv Syst 39: 61–72.
11.
Dubowitz, V. (1985) Muscle Biopsy. A Practical Approach. London, Baillière, Tindall, pp 29–34.
12.
Ekblad, E., L. Edvinsson, C. Wahlestedt, R. Uddman, R. Håkansson, F. Sundler (1984) Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers. Regul Pept 8: 225–235.
13.
Ekelund, U., D. Erlinge (1997) In vivo receptor characterization of neuropeptide Y-induced effects in consecutive vascular sections of cat skeletal muscle. Br J Pharmacol 120: 387–392.
14.
Ferrell, W.R., A. Khoshbaten, W.J. Angerson (1990) Responses of bone and joint blood vessels in cats and rabbits to electrical stimulation of nerves supplying the knee. J Physiol 431: 677–687.
15.
Folkow, B., B. Uvnäs (1948) The distribution and functional significance of sympathetic vasodilators to the hindlimbs of the cat. Acta Physiol Scand 15: 389–400.
16.
Foreman, J.C. (1987) Peptides and neurogenic inflammation. Br Med Bull 43: 386–400.
17.
Forsgren, S. (1986) The distribution of sympathetic nerve fibers in the AV-node and AV-bundle of bovine heart. Histochem J 18: 625–638.
18.
Forsgren, S., L. Söderberg (1987) Immunohistochemical procedures for the demonstration of peptide- and tyrosine hyrdoxylase-containing nerve fibers in cryostat sections of unfixed rabidly frozen tissue stored for long periods of time. A study on heart tissue. Histochemistry 87: 561–568.
19.
Gibbins, I.L., (1992) Vasoconstrictor, vasodilator and pilomotor pathways in sympathetic ganglia of guinea-pigs. Neuroscience 47: 657–672.
20.
Gibbins, I.L., J.L. Morris, J.B. Furness, M. Costa (1988) Innervation of systemic blood vessels; in Burnstock, G., S.G. Griffith (eds): Nonadrenergic Innervation of Blood Vessels. Boca Raton, CRC Press, pp 1–36.
21.
Gorczynski, R.J., B. Klitzman, B.R. Duling (1978) Interrelations between contracting striated muscle and precapillary microvessels. Am J Physiol 235: 494–504.
22.
Grasby, D.J., I.L. Gibbins, J.L. Morris (1997) Projections of sympathetic nonnoradrenergic neurons to skeletal muscle arteries in guinea-pig limbs vary with the metabolic character of muscles. J Vasc Res 34: 351–364.
23.
Hansson, M., S. Forsgren (1995) Immunoreactive atrial and brain natriuretic peptides are co-localized in Purkinje fibres but not in the innervation of the bovine heart conduction system. Histochem J 27: 222–230.
24.
Hara, H., G.S. Hamill, D.M. Jacobowitz (1985) Origin of cholinergic nerves to the rat major cerebral arteries: Coexistence with vasoactive intestinal polypeptide. Brain Res Bull 14: 179–188.
25.
Hill, E.L., R. Elde (1991) Distribution of CGRP-, VIP-, DβH-, SP- and NPY-immunoreactive nerves in the periosteum of the rat. Cell Tissue Res 264: 469–480.
26.
Hohmann, G. (1933) Das Wesen und die Behandlung des sogenannten Tennisellenbogens. Münch Med Wochenschr 80: 250–252.
27.
Jährhult, J., P. Hellstrand, F. Sundler (1980) Immunohistochemical localisation and vascular effects of vasoactive intestinal polypeptide in skeletal muscle of the cat. Cell Tissue Res 207: 55–64.
28.
Kannus, P., L. Józsa (1991) Histopathological changes preceding spontaneous rupture of a tendon. J Bone Joint Surg 73A: 1507–1525.
29.
Koizumi, K., R. Collin, A. Kaufman, C.M. Brooks (1970) Contribution of unmyelinated afferent excitation to sympathetic reflexes. Brain Res 20: 99–106.
30.
Konttinen, Y.T., S. Santavirta, P. Paavolainen, I. Antti-Poika, T. Tiainen, D. Nordström, M. Hukkanen (1992) Immunoreactive neuropeptide nerves in ligamentous tissue in chronic shoulder pain. Arch Orthop Trauma Surg 111: 341–344.
31.
Levine, J.D., S.J. Dardick, M.F. Roizen, C. Helms, A.I. Basbaum (1986) Contribution of sensory afferents and sympathetic efferents to joint injury in experimental arthritis. J Neurosci 6: 3423–3429.
32.
Lewis Carl, S.A., I. Gilette-Ferguson, D.G., Ferguson (1993) An indirect immunofluorescence procedure for staining the same cryosection with two mouse monoclonal primary antibodies. J Histochem Cytochem 41: 1273–1278.
33.
Lieber, R.L., B.-O. Ljung, J. Fridén (1997) Sarcomere length in wrist extensor muscles. Changes may provide insights into the etiology of chronic lateral epicondylitis. Acta Orthop Scand 68: 249–254.
34.
Ljung, B.-O., S. Forsgren, J. Fridén (1999) Substance P and CGRP expression at the extensor carpi radialis brevis muscle origin: Implications for the etiology of tennis elbow. J Orthop Res, in press.
35.
Lundberg, J.M., A. Änggård, J. Fahrenkrug, T. Hökfelt, V. Mutt (1980) Vasoactive intestinal polypeptide in cholinergic neurons of exocrine glands: Functional significance of coexisting transmitters for vasodilation and secretion. Proc Natl Acad Sci USA 77: 1651–1655.
36.
Lundberg, J.M., L. Terenius, T. Hökfelt, C.R. Martling, K. Tatemoto, V. Mutt, J. Polak, S.R. Bloom, M. Goldstein (1982) Neuropeptide Y-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand 116: 447–480.
37.
McDougall, J.J., R.C. Bray, K.A. Sharkey (1997) Morphological and immunohistochemical examination of nerves in normal and injured collateral ligaments of rat, rabbit and human knee joints. Anat Rec 248: 29–39.
38.
Nakayama, K., S. Masuko, T. Tsuruta, T. Kutsuna, H. Watanabe (1995) Vascularization and innervation of the canine wrist joint synovial membrane. Tohoku J Exp Med 175: 195–209.
39.
Nirschl, R.P. (1992) Elbow tendinosis/tennis elbow. Clin Sports Med 11: 851–870.
40.
Öhlén, A., Å. Thuresson-Klein, L. Lindbom, T. Hökfelt, P. Hedqvist (1988) Substance P and NPY innervation of microvessels in the rabbit tenuissimus muscle. Microvasc Res 36: 117–129.
41.
Palmgren, T., M. Grönblad, J. Virri, S. Seitsalo, M. Ruuskanen, E. Karaharju (1996) Immunohistochemical demonstration of sensory and autonomic nerve terminals in herniated lumbar disc tissue. Spine 21: 1301–1306.
42.
Pedersen-Bjergaard, U., L. Bøgeskov Nielsen, K. Jensen, L. Edvinsson, I. Jansen, J. Olesen (1991) Calcitonin gene-related peptide, neurokinin A and substance P: Effects on nociception and neurogenic inflammation in human skin and temporal muscle. Peptides 12: 333–337.
43.
Potter, E.K. (1988) Neuropeptide Y as an autonomic neurotransmitter. Pharmacol Ther 37: 251–273.
44.
Rathbun, J.B., I. Macnab (1970) The microvascular pattern of the rotator cuff. J Bone Joint Surg 52A: 540–553.
45.
Regan, W., L.E. Wold, R. Coonrad, B.F. Morrey (1992) Microscopic histopathology of chronic refractory lateral epicondylitis. Am J Sports Med 20: 746–749.
46.
Riley, G.P., R.L. Harrall, C.R. Constant, M.D. Chard, T.E. Cawston, B.L. Hazleman (1994) Tendon degeneration and chronic shoulder pain: Changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis. Ann Rheum Dis 53: 359–366.
47.
Roberts, W.J., S.M. Elardo (1985) Sympathetic activation of A-delta nociceptors. Somatosens Res 3: 33–44.
48.
Rothman, R.H., W.W. Parke (1965) The vascular anatomy of the rotator cuff. Clin Orthop 41: 176–186.
49.
Said, S.I., V. Mutt (1970) Polypeptide with broad biological activity: Isolation from small intestine. Science 169: 1217–1218.
50.
Said, S.I., V. Mutt (1972) Isolation from porcine intestinal wall of a vasoactive octacosapeptide related to secretin and to glucagon. Eur J Biochem 28: 199–204.
51.
Scott, D.T., F.Y. Lam, W.R. Ferrell (1994) Acute joint inflammation. Mechanisms and mediators. Gen Pharmacol 25: 1285–1296.
52.
Segal, S.S., B.R. Duling (1986) Communication between feed arteries and microvessels in hamster striated muscle: Segmental vascular responses are functionally coordinated. Circ Res 59: 283–290.
53.
Smith, R.W., R. Papadopolous, R. Mani, M.I.D. Cawley (1994) Abnormal microvascular responses in lateral epicondylitis. Br J Rheumatol 33: 1166–1168.
54.
Tatemoto, K., M. Carlqvist, V. Mutt (1982) Neuropeptide Y – a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 296: 659–660.
55.
Tenne, J., C.R. Anderson (1995) Chemically-identified autonomic pathways through rat lumbar sympathetic chain ganglia. Proc Aust Neurosci Soc 6: 175.
56.
Wiesenfeld-Hallin, Z., X.-J. Xu (1993) The differential roles of substance P and neurokinin A in spinal cord hyperexcitability and neurogenic inflammation. Regul Pept 46: 165–173.
57.
Wong, H.Y., (1993) Neural mechanisms of joint pain. Ann Acad Med Singapore 22: 646–650.
1999
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.