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562.11 Nociceptor Afferent Drive Alters SI Neuron Response to Mechanical Stimulation of the RF
Barry L. Whitsel1, Oleg V. Favorov
1, Yongbiao Li2, Jaekwang Lee
1and Mark Tommerdahl
1
1Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599; 2Sloan-Kettering Cancer Ctr., New York, NY
INTRODUCTION
Human psychophysical studies have demonstrated that
clinical pain or investigator-evoked nociceptor afferent activity
is accompanied by degradation of the perceptual abilities to
detect and discriminate vibrotactile skin stimulation.
The present study sought to address deficiency in current
neuromechanistic understanding of pain-tactile interactions by
evaluating the effect(s) on SI cortical cutaneous
mechanoresponsive neurons of two procedures that evoke
pain in a conscious subject – (1) skin contact with a 47-51 C
probe, and (2) intradermal injection of capsaicin .
RESULTS
METHODS
FIGURE 9. Competitive interactions between area 3a and areas 3b/1.
Optical imaging of SI response to thermo-neutral and thermo-noxious tactile
stimulation. Green rectangles indicate regions of interest in area 3a and in areas
3b/1. B: Skin flutter stimuli were delivered to the hand via a temperature-
controlled 5mm-diameter mechanical probe. C: Development of the SI optical
response pattern across a series of time frames after the stimulus onset. Note
that the 38˚C stimulus evokes the optical response in areas 3b and 1 (top row),
and only a transient response in area 3a. In contrast, the noxious 52˚C stimulus
evokes a major response in area 3a, while suppressing the response in areas 3b
and 1 (bottom row).
FIGURE 1. Optical imaging of SI response to thermo-neutral and thermo-noxious
tactile stimulation. Skin indent (A) or flutter (B) stimuli were delivered to the hand
via a temperature-controlled 5mm-diameter mechanical probe. Stimulus amplitude
– 200 m, frequency – 25Hz, duration – 4s, probe temperature – either neutral 30˚C
or noxious 48˚C.
Note that the 30˚C stimuli evoke stronger optical response in areas 3b and 1 than
do the noxious 48˚C stimuli.
In anesthetized (0.1-0.5% halothane in a 50/50 N2O/O2
mixture) squirrel monkeys, extracellular recordings of the spike
discharge activity of rapidly-adapting (RA) neurons in areas 3b
and 1 of primary somatosensory cortex (SI) were obtained
before, during, and following 25Hz sinusoidal vertical skin
displacement stimulation of the receptive field center. The
stimulating probe was kept at either neutral or noxious
temperature.
FIGURE 2. Responses of an exemplary RA neuron, isolated in area 3b, to
50 m near-threshold (left panel) and 200 m supra-threshold (right panel)
25Hz flutter stimulation. The first and the last 6 trials were delivered at a
neutral 38 C temperature; trials 7-12 were delivered at a noxious 48 C
temperature.
NEAR-THRESHOLD SUPRA-THRSHOLD
POPULATION (n = 35) SUMMARY
The response evoked by near-threshold (10-50 m) stimulation with a 47-51 C
probe is lower in mean firing rate than the response evoked by stimulation with a
25-38 C probe. In contrast, when the stimulus is suprathreshold (100-400 m), no
suppression of RA neuron MFR accompanies stimulation with a 47-51 C probe.
The spike firing evoked by near-threshold stimulation with a 47-51 C probe is
less phase-locked (“entrained”) to the stimulus than the activity evoked by
stimulation with a 25-38 C probe. In contrast, when the stimulus is
suprathreshold, no suppression of entrainment accompanies stimulation with a
47-51 C probe.
EFFECT OF INTRADERMAL CAPSAICIN INJECTION
FIGURE5. Effect of capsaicin
injection on spontaneous activity in
area 3b.
FIGURE 6. Capsaicin injection
has a suppressive effect on
area 3b neuron response to
near-threshold flutter
stimulation, comparable to the
effect of noxious heat.
FIGURE 7. Capsaicin injection has a facilitatory effect on area 3b neuron
response to supra-threshold thermoneutral flutter stimulation.
PUTATIVE MECHANISMS
FIGURE 8. Relevant
pathways.
CONCLUSION
An activity-dependent, bipolar action of GABA on the response
of SI RA neurons to mechanical skin stimulation might underlie
the diverse and seemingly conflicting effects of pain/
nociceptive afferent drive on human tactile perception.
Figure 10. Response of RS neurons
to GABA puffs following activation of
thalamic pathway. Depolarization was
observed in the recorded RS neuron
when GABA (0.1 - 1 mM) was applied
after 1s 20Hz electrical stimulation.
Figure 11. Polarity of GABA action in 10 RS
neurons was reversed in activity- and time-
dependent manner.
Figure 12. Activation of GABAA
receptors by isoguvacine
enhanced Ca2+ influx in activity-
dependent manner in individual
cells.