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.