Effects of peripheral nerve injury on parvalbumin expression in adult rat dorsal root ganglion neurons.

Tom Medici,Peter J Shortland

doi:10.1186/s12868-015-0232-9

Abstract

BackgroundParvalbumin (PV) is a calcium binding protein that identifies a subpopulation of proprioceptive dorsal root ganglion (DRG) neurons. Calcitonin gene-related peptide (CGRP) is also expressed in a high proportion of muscle afferents but its relationship to PV is unclear. Little is known of the phenotypic responses of muscle afferents to nerve injury. Sciatic nerve axotomy or L5 spinal nerve ligation and section (SNL) lesions were used to explore these issues in adult rats using immunocytochemistry.ResultsIn naive animals, the mean PV expression was 25 % of L4 or L5 dorsal root ganglion (DRG) neurons, and this was unchanged 2 weeks after sciatic nerve axotomy. Colocalization studies with the injury marker activating transcription factor 3 (ATF3) showed that approximately 24 % of PV neurons expressed ATF3 after sciatic nerve axotomy suggesting that PV may show a phenotypic switch from injured to uninjured neurons. This possibility was further assessed using the spinal nerve ligation (SNL) injury model where injured and uninjured neurons are located in different DRGs. Two weeks after L5 SNL there was no change in total PV staining and essentially all L5 PV neurons expressed ATF3. Additionally, there was no increase in PV-ir in the adjacent uninjured L4 DRG cells. Co-labelling of DRG neurons revealed that less than 2 % of PV neurons normally expressed CGRP and no colocalization was seen after injury.ConclusionThese experiments clearly show that axotomy does not produce down regulation of PV protein in the DRG. Moreover, this lack of change is not due to a phenotypic switch in PV immunoreactive (ir) neurons, or de novo expression of PV-ir in uninjured neurons after nerve injury. These results further illustrate differences that occur when muscle afferents are injured as compared to cutaneous afferents.

Highlights

Parvalbumin (PV) is a calcium binding protein that identifies a subpopulation of proprioceptive dorsal root ganglion (DRG) neurons
Peripheral nerve injury disconnects sensory and motor axons from their peripheral targets and results in the production of regeneration associated genes such as α-tubulin, GAP43, CAP23, activating transcription factor 3 (ATF3), and STAT3 that are important in the growth and functional recovery of damaged sensory and motor axons [1, 2]
Similar percentages were expressed in both ganglia and there was no statistical difference between the ganglia (t7 = 0.255, P > 0.5, 2-tailed test)

Summary

Introduction

Parvalbumin (PV) is a calcium binding protein that identifies a subpopulation of proprioceptive dorsal root ganglion (DRG) neurons. Directly injured neurons can upregulate neurotransmitters such as NPY, BDNF, galanin whilst adjacent uninjured neurons can increase their content of neurotransmitters such as substance P, CGRP, BDNF, galanin and ion channels such as TRPRV1 and P2X3 [3,4,5]. This plasticity is thought to contribute to the generation and maintenance of neuropathic pain [3, 6, 7]. When the gastrocnemius (muscle) or Medici and Shortland BMC Neurosci (2015) 16:93 tibial (mixed) or sural (cutaneous) nerve was sectioned, mechanical and thermal hypersensitivity only occurred in nerve injuries involving muscle afferents [10]

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