Calcitonin gene-related peptide immunoreactive DRG neurons innervating the cervical facet joints show phenotypic switch in cervical facet injury in rats

Abstract. Patients with cervical facet lesions and facet joint injury sometimes experience diffuse neck pain, headache, and arm and shoulder pain. However, the pathophysiology of the intensity and expansion of facet joint pain has not yet been investigated. Retrograde transport of fluoro-gold (F-G) and immunohistochemistry of calcitonin gene-related peptide (CGRP) was used in 20 rats (control group, n=10; injured group, n=10). For the injured group, the whole facet capsule was incised. Of the total F-G labelled dorsal root ganglion (DRG) neurons innervating the C5/6 facet joint, the number and the cross-sectional area of cell profiles of F-G labelled CGRP-ir neurons were evaluated in the bilateral DRGs of both groups. The numbers of CGRP-ir F-G labelled DRG neurons as a percentage of all F-G labelled DRG neurons at C3, C4, C5, C6, C7, C8, T1, T2, and T3 respectively were 30, 22, 43, 47, 21, 19, 25, 36 and 30% in the control group, and 13, 15, 23, 17, 15, 8, 16, 28 and 35% in the injured group, with the injured group showing a significantly lower percentage of CGRP-ir F-G labelled neurons than the control group at C5 and C6 (P<0.05). However, the mean cross-sectional area of F-G labelled CGRP-ir cells from C3 to C8 DRGs increased from 625±22 µm2 to 878±33 µm2 in the injured group (P<0.001). Associated with the injured facet joints, the phenotypic switch to large neurons may complicate the mechanism of injured facet pain.

[1]  R. Coggeshall,et al.  Peripheral nerve injury triggers central sprouting of myelinated afferents , 1992, Nature.

[2]  N. Bogduk,et al.  The cervical zygapophysial joints as a source of neck pain. , 1988, Spine.

[3]  R. Coggeshall,et al.  Reorganization of central terminals of myelinated primary afferents in the rat dorsal horn following peripheral axotomy , 1995, The Journal of comparative neurology.

[4]  T. Fukuoka,et al.  Substance P induced by peripheral nerve injury in primary afferent sensory neurons and its effect on dorsal column nucleus neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  S. Ohtori,et al.  Calcitonin gene-related peptide immunoreactive sensory DRG neurons innervating the cervical facet joints in rats , 2002, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[6]  H. Higashi,et al.  Functional reorganization of sensory pathways in the rat spinal dorsal horn following peripheral nerve injury , 2001, The Journal of physiology.

[7]  K. Hayashi,et al.  Motion analysis of cervical vertebrae during whiplash loading. , 1999, Spine.

[8]  C. Woolf.  Evidence for a central component of post-injury pain hypersensitivity , 1983, Nature.

[9]  R. Coggeshall,et al.  Sprouting of Aβ fibers into lamina II of the rat dorsal horn in peripheral neuropathy , 1996, Neuroscience Letters.

[10]  S. Ohtori,et al.  Sensory Innervation of the Cervical Facet Joints in Rats , 2001, Spine.

[11]  N. Bogduk.  The Clinical Anatomy of the Cervical Dorsal Rami , 1982, Spine.

[12]  S Inami,et al.  Immunohistochemical demonstration of nerve fibers in the synovial fold of the human cervical facel joint , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[13]  Kazuhisa Takahashi,et al.  CGRP-immunoreactive nerve fibers projecting to lumbar facet joints through the paravertebral sympathetic trunk in rats , 1996, Neuroscience Letters.

[14]  T. Hökfelt.  Neuropeptides in perspective: The last ten years , 1991, Neuron.

[15]  S. Lawson,et al.  Cell type and conduction velocity of rat primary sensory neurons with calcitonin gene-related peptide-like immunoreactivity , 1990, Neuroscience.

[16]  N. Bogduk,et al.  The Prevalence of Chronic Cervical Zygapophysial Joint Pain After Whiplash , 1995, Spine.

[17]  G. Bashford,et al.  Diagnostic cervical zygapophyseal joint blocks for chronic cervical pain. , 2001, The Medical journal of Australia.

[18]  S. Nakamura,et al.  Innervation of the Lumbar Facet Joints: Origins and Functions , 1997, Spine.

[19]  T. Fukuoka,et al.  Calcitonin gene-related peptide increase in the rat spinal dorsal horn and dorsal column nucleus following peripheral nerve injury: Up-regulation in a subpopulation of primary afferent sensory neurons , 1997, Neuroscience.

[20]  J. Polak,et al.  Morphological basis for back pain: the demonstration of nerve fibers and neuropeptides in the lumbar facet joint capsule but not in ligamentum flavum. , 1992, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.