Identity of myelinated cutaneous sensory neurons projecting to nocireceptive laminae following nerve injury in adult mice.
It is widely thought that, after peripheral injury, some low-threshold mechanoreceptive (LTMR) afferents "sprout" into pain-specific laminae (I-II) of the dorsal horn and are responsible for chronic pain states such as mechanical allodynia. Although recent studies have questioned this hypothesis, they fail to account for a series of compelling results from single-fiber analyses showing extensive projections from large-diameter myelinated afferents into nocireceptive layers after nerve injury. Here we show that, in the thoracic spinal cord of naïve adult mouse, all myelinated nociceptors gave rise to terminal projections throughout the superficial dorsal horn laminae (I-II). Most (70%) of these fibers had large-diameter axons with recurving flame-shaped central arbors that projected throughout the dorsal horn laminae I-V. This morphology was reminiscent of that attributed to sprouted LTMRs described in previous studies. After peripheral nerve axotomy, we found that LTMR afferents with narrow, uninflected somal action potentials did not sprout into superficial laminae of the dorsal horn. Only myelinated noiceptive afferents with broad, inflected somal action potentials were found to give rise to recurving collaterals and project into superficial "pain-specific" laminae after axotomy. We conclude that the previously undocumented central morphology of large, myelinated cutaneous nociceptors may very well account for the morphological findings previously thought to require sprouting of LTMRs.
Woodbury
C Jeffery
CJ
Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Kullmann
Florenta A
FA
McIlwrath
Sabrina L
SL
Koerber
H Richard
HR
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D019771:Axotomy / Q000379:methods; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002772:Cholera Toxin / Q000378:metabolism; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000473:pathology; D008297:Male; D051379:Mice; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D010523:Peripheral Nervous System Diseases / Q000473:pathology*; D021381:Protein Transport / Q000502:physiology; D012867:Skin / Q000294:innervation*; D013376:Substantia Gelatinosa / Q000473:pathology*
C070614:neurobiotin; D001710:Biotin; D002772:Cholera Toxin; D015740:Calcitonin Gene-Related Peptide