Processing noxious information at the subnucleus reticularis dorsalis (SRD) of anesthetized cats: wind-up mechanisms
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Processing noxious information at the subnucleus reticularis dorsalis (SRD) of anesthetized cats : wind-up mechanisms. / Soto, Cristina; Martín-Cora, Francisco J; Leiras, Roberto; Velo, Patricia; Canedo, Antonio.
In: Pain, Vol. 140, No. 1, 15.11.2008, p. 190-208.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Processing noxious information at the subnucleus reticularis dorsalis (SRD) of anesthetized cats
T2 - wind-up mechanisms
AU - Soto, Cristina
AU - Martín-Cora, Francisco J
AU - Leiras, Roberto
AU - Velo, Patricia
AU - Canedo, Antonio
PY - 2008/11/15
Y1 - 2008/11/15
N2 - With the exception of one monkey's study, where wind-up was not reported, electrophysiological data from SRD neurons were obtained in rodents where they show wind-up. This work was designed to examine the response properties of SRD neurons in anesthetized cats to study how general the data from rats may be. Since cat's SRD cells showed wind-up, its underlying mechanisms were approached, an issue not previously addressed at supraspinal level. Electrical stimulation, extracellular (combined with microiontophoresis) and intracellular techniques revealed that A delta information reaches the SRD via the ventrolateral cord, whereas C information preferentially follows a dorsal route. Wind-up was usually generated by spinal and peripheral stimulation, but it was also evoked either by stimulating the nucleus reticularis gigantocellularis (NRGc), even after spinal cord section and bilateral full thickness removal of the cerebral cortex, or by applying microiontophoretic pulses of l-glutamate at 0.3-1 Hz. Wind-up relied on afferent repetitive activity gradually depolarizing the SRD neurons leading 3-4.5 Hz subthreshold membrane rhythmic activity to threshold. Riluzole retarded wind-up generation and decreased the number of spikes per stimulus during wind-up. GABA or glycine abolished spontaneous and sensory-evoked activity and bicuculline, but not strychnine, increased spontaneous and stimulus-evoked activity. These results demonstrate that wind-up at the SRD is not merely the reflection of spinal wind-up, but (i) can be locally generated, (ii) is partially dependent upon persistent sodium currents, and (iii) is under the modulation of a tonic GABAa-dependent inhibition decreasing SRD excitability. Injury and/or inflammation producing tonic C-fiber activation will surpass tonic inhibition generating wind-up.
AB - With the exception of one monkey's study, where wind-up was not reported, electrophysiological data from SRD neurons were obtained in rodents where they show wind-up. This work was designed to examine the response properties of SRD neurons in anesthetized cats to study how general the data from rats may be. Since cat's SRD cells showed wind-up, its underlying mechanisms were approached, an issue not previously addressed at supraspinal level. Electrical stimulation, extracellular (combined with microiontophoresis) and intracellular techniques revealed that A delta information reaches the SRD via the ventrolateral cord, whereas C information preferentially follows a dorsal route. Wind-up was usually generated by spinal and peripheral stimulation, but it was also evoked either by stimulating the nucleus reticularis gigantocellularis (NRGc), even after spinal cord section and bilateral full thickness removal of the cerebral cortex, or by applying microiontophoretic pulses of l-glutamate at 0.3-1 Hz. Wind-up relied on afferent repetitive activity gradually depolarizing the SRD neurons leading 3-4.5 Hz subthreshold membrane rhythmic activity to threshold. Riluzole retarded wind-up generation and decreased the number of spikes per stimulus during wind-up. GABA or glycine abolished spontaneous and sensory-evoked activity and bicuculline, but not strychnine, increased spontaneous and stimulus-evoked activity. These results demonstrate that wind-up at the SRD is not merely the reflection of spinal wind-up, but (i) can be locally generated, (ii) is partially dependent upon persistent sodium currents, and (iii) is under the modulation of a tonic GABAa-dependent inhibition decreasing SRD excitability. Injury and/or inflammation producing tonic C-fiber activation will surpass tonic inhibition generating wind-up.
KW - Afferent Pathways/physiopathology
KW - Anesthesia
KW - Animals
KW - Cats
KW - Female
KW - Male
KW - Medulla Oblongata/physiopathology
KW - Neurons
KW - Pain/physiopathology
KW - Spinal Cord/physiopathology
U2 - 10.1016/j.pain.2008.08.007
DO - 10.1016/j.pain.2008.08.007
M3 - Journal article
C2 - 18799268
VL - 140
SP - 190
EP - 208
JO - Pain
JF - Pain
SN - 0304-3959
IS - 1
ER -
ID: 249307757