Reorganization of muscle afferent projections accompanies peripheral nerve regeneration

doi:10.1016/0306-4522(81)90043-9

Neuroscience

Volume 6, Issue 10, October 1981, Pages 2053-2057, 2059-2061

https://doi.org/10.1016/0306-4522(81)90043-9 Get rights and content

Abstract

Dorsal horn projections from muscle innervated by the common peroneal branch of the rat sciatic nerve were studied in three experimental situations: after either epineurial or individual fascicular suture of the sciatic nerve, or after isolated severance and repair of the peroneal sciatic fascicle. Four months after surgery, the peroneal-innervated muscles were injected with a conjugate of horseradish peroxidase and wheatgerm agglutinin. Projections from these muscles, as well as from peroneal-innervated skin and the entire sciatic nerve, were also studied in normal controls. Rats were perfused forty-eight hours after enzyme exposure, and the presence of horseradish peroxidase demonstrated by reaction of spinal cord sections with H₂O₂ and tetramethylbenzidine.

Injection of normal peroneal-innervated muscle labeled a sharply-defined area within the substantia gelatinosa of the ipsilateral dorsal horn. After regeneration from individual fascicular sciatic repair, or suture of the isolated peroneal fascicle, this projection was more widespread, resembling that from normal peroneal-innervated skin. The muscle projection was even wider and more variable following epineurial repair, yet always confined within the normal sciatic projection. The width and variability of muscle projections after epineurial suture probably reflect inter-fascicular misdirection of regenerating axons. The finding of expanded projections even after partial (individual fascicular) and total (isolated peroneal repair) elimination of this misdirection, and the similarity of these projections to those of peroneal-innervated skin, suggest confusion at the intra-fascicular level as well. Muscle could be reinnervated by peroneal nerve axons which previously served non-muscular structures, and which project to a wider area of the dorsal horn not originally labeled by muscle injection.

These experiments demonstrate a substantial projection from muscle to the substantia gelatinosa, an area strongly implicated in the processing of nociceptive information. Reorganization of these projections might provide an anatomical substrate for abnormal pain perception after peripheral nerve injury, including confusion as to its tissue of origin. Furthermore, this reorganization is not eliminated by individual fascicular suture. This technique, which decreases the frequency with which regenerating axons cross from one fascicle to another, does not, therefore, prevent axon disorganization within the fascicle itself.

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Loss of dorsal root ganglion neuron, or injury to dorsal roots, induces permanent somatosensory defect without therapeutic option. We explored an approach to restoring hind limb somatosensory innervation after elimination of L4, L5 and L6 dorsal root ganglion neurons in rats. Somatosensory pathways were reconstructed by connecting L4, L5 and L6 lumbar dorsal roots to T10, T11 and T12 intercostal nerves, respectively, thus allowing elongation of thoracic ganglion neuron peripheral axons into the sciatic nerve. Connection of thoracic dorsal root ganglion neurons to peripheral tissues was documented 4 and 7 months after injury. Myelinated and unmyelinated fibers regrew in the sciatic nerve. Nerve terminations expressing calcitonin-gene-related-peptide colonized the footpad skin. Retrograde tracing showed that T10, T11 and T12 dorsal root ganglion neurons expressing calcitonin-gene-related-peptide or the neurofilament RT97 projected axons to the sciatic nerve and the footpad skin. Recording of somatosensory evoked potentials in the upper spinal cord indicated connection between the sciatic nerve and the central nervous system. Hind limb retraction in response to nociceptive stimulation of the reinnervated footpads and reversion of skin lesions suggested partial recovery of sensory function. Proprioceptive defects persisted. Delayed somatosensory reinnervation of the hind limb after destruction of lumbar dorsal root neurons in rats indicates potential approaches to reduce chronic disability after severe injury to somatosensory pathways.
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Peripheral nerves innervating muscles have sensory fibers that relay information into the CNS information about proprioception, pain, and the metabolic state of the muscle. The present study shows the primary afferent projections into the spinal cord of the nerves innervating the gastrocnemius muscle of the rat using the transganglionic transport of a cocktail of horseradish peroxidase (HRP) conjugated to cholera toxin and wheat germ agglutinin; these markers have been shown to label large and small fibers, respectively. A dense projection into lamina I of the lumbar dorsal horn and a more moderate projection into lamina V were seen. Moreover, dense reaction product was found in the most medial aspect of lamina II, especially lamina II inner part, and less in lamina III and IV of levels L3–L5. Lamina VI had dense reaction product from the rostral sacral levels of the spinal cord that continued into Clarke’s column at rostral lumbar levels. The nucleus gracilis also was labeled.
Other nerves emerging from the popliteal fossa, including the tibial, peroneal, and sural nerves, also were injected with the HRP cocktail and their projections compared with those from the gastrocnemius muscle. Projections from the gastrocnemius muscle only partially overlapped with those from the tibial nerve, from which the nerves to the gastrocnemius muscle branch. However, the topology of projections from these nerves to laminae II-IV of the dorsal horn differed from that of the nerves of the gastrocnemius muscle, suggesting there was little spread to other nerves in the popliteal fossa. It was also noted that large labeled processes, presumably dendrites of retrogradely labeled motoneurons, entered the dorsal horn. These data provide information on the central projections of both the large and small fibers innervating the gastrocnemius muscle, and may aid in determining the circuitry utilized in the exercise pressor reflex as well as muscle pain.
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Reorganization of muscle afferent projections accompanies peripheral nerve regeneration

Abstract

Neuroscience Letters

Brain Res.

Brain Res.

Brain Res.

Neuroscience

Brain Res.

Activation des fibres afférentes améyéliniques d'origine musculaire

C. R. Séanc. Soc. Biol.

Etude des récepteurs musculaires innervés par les fibres afférentes du groupe III (fibres myélinisées fines), chez le chat

Archs Ital. Biol.

Transperikaryal transport of horseradish peroxidase along sensory nerves in the rat

Soc. Neurosci. Abstr.

Alteration in connections between muscle and anterior horn motoneurons after peripheral nerve repair

Science, N.Y.

A comparison of motoneuron pool organization after epineurial and perineurial repair of the rat sciatic nerve

Ortho. Trans.

Reconstructive Microsurgery

Reorganization of spinal cord sensory map after peripheral nerve injury

Nature, Lond.

Peripheral nerve suture

Acta. chir. scand.

Phenomena due to misdirection of regenerating fibers of cranial, spinal and autonomic nerves

Archs Surg. Chicago

Superior sensitivity of conjugates of horseradish peroxidase with wheat germ agglutinin for studies of retrograde axonal transport

J. Histochem. Cytochem.

Anatomy of the Rat

Faulty sensory localization in nerve regeneration. An index of functional recovery following suture

J. Neurosurg.

Guidance of regrowing sensory axons after cutaneous nerve lesions in the cat

J. Neurophysiol.

Non-myelinated afferent fibers from mammalian skeletal muscle

J. Physiol., Lond.