Non-Peptidergic Nociceptive Neurons Are Essential for Mechanical Inflammatory Hypersensitivity in Mice

Small nerve fibers that bind the isolectin B4 (IB4 + C-fibers) are a subpopulation of primary afferent neurons that are involved in nociceptive sensory transduction and do not express the neuropeptides substance P and calcitonin-gene related peptide (CGRP). Several studies have attempted to elucidat...

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Veröffentlicht in:Molecular neurobiology Jg. 56; H. 8; S. 5715 - 5728
Hauptverfasser: Pinto, Larissa G., Souza, Guilherme R., Kusuda, Ricardo, Lopes, Alexandre H., Sant’Anna, Morena B., Cunha, Fernando Q., Ferreira, Sérgio H., Cunha, Thiago M.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York Springer US 01.08.2019
Springer Nature B.V
Schlagworte:
Animal models
Animals
Biomedical and Life Sciences
Biomedicine
Calcitonin
Calcitonin gene-related peptide
Capsaicin receptors
Cell Biology
Dinoprostone - metabolism
Dorsal root ganglia
Epinephrine
Fibers
Glial cell line-derived neurotrophic factor
Glial Cell Line-Derived Neurotrophic Factor - pharmacology
Hypersensitivity
Hypersensitivity - complications
Hypersensitivity - pathology
Hypersensitivity - physiopathology
Inflammation
Inflammation - complications
Inflammation - pathology
Inflammation - physiopathology
Labeling
Lectins - pharmacology
Male
Mice, Inbred C57BL
Nerve Fibers, Unmyelinated - metabolism
Nerve growth factor
Neurobiology
Neurology
Neuronal-glial interactions
Neuropeptides
Neurosciences
Nociception - drug effects
Nociceptors
Nociceptors - drug effects
Nociceptors - pathology
Pain - complications
Pain - physiopathology
Pain perception
Peptides
Peptides - metabolism
Prostaglandin E2
Saporin
Saporins - pharmacology
Sensory neurons
Sensory transduction
Spinal cord
Substance P
Transient receptor potential proteins
Nociceptors
IB4-saporin
Mice
Inflammatory pain
Non-peptidergic C-fibers
Mechanical hypersensitivity
ISSN:0893-7648, 1559-1182, 1559-1182
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Zusammenfassung:Small nerve fibers that bind the isolectin B4 (IB4 + C-fibers) are a subpopulation of primary afferent neurons that are involved in nociceptive sensory transduction and do not express the neuropeptides substance P and calcitonin-gene related peptide (CGRP). Several studies have attempted to elucidate the functional role of IB4 + -nociceptors in different models of pain. However, a functional characterization of the non-peptidergic nociceptors in mediating mechanical inflammatory hypersensitivity in mice is still lacking. To this end, in the present study, the neurotoxin IB4-Saporin (IB4-Sap) was employed to ablate non-peptidergic C-fibers. Firstly, we showed that intrathecal (i.t.) administration of IB4-Sap in mice depleted non-peptidergic C-fibers, since it decreased the expression of purinoceptor 3 (P2X 3 ) and transient receptor potential cation channel subfamily V member 1 (TRPV1) in the dorsal root ganglia (DRGs) as well as IB4 labelling in the spinal cord. Non-peptidergic C-fibers depletion did not alter the mechanical nociceptive threshold, but it inhibited the mechanical inflammatory hypersensitivity induced by glial cell-derived neurotrophic factor (GDNF), but not nerve growth factor (NGF). Depletion of non-peptidergic C-fibers abrogated mechanical inflammatory hypersensitivity induced by carrageenan. Finally, it was found that the inflammatory mediators PGE 2 and epinephrine produced a mechanical inflammatory hypersensitivity that was also blocked by depletion of non-peptidergic C-fibers. These data suggest that IB4-positive nociceptive nerve fibers are not involved in normal mechanical nociception but are sensitised by inflammatory stimuli and play a crucial role in mediating mechanical inflammatory hypersensitivity.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0893-7648
1559-1182
1559-1182
DOI:10.1007/s12035-019-1494-5