Area-specific representation of mechanical nociceptive stimuli within SI cortex of squirrel monkeys

Abstract

While functional imaging studies in humans have consistently reported activation of primary somatosensory cortex (SI) with painful stimuli, the specific roles of subdivisions of areas 3a, 3b, and 1 within SI during pain perception are largely unknown, particularly in the representation of mechanical evoked pain. In this study, we investigated how modality, location, and intensity of nociceptive stimuli are represented within SI by using high-spatial resolution optical imaging of intrinsic signals in Pentothal-anesthetized squirrel monkeys. Perceptually comparable mechanical nociceptive and innocuous tactile stimuli were delivered by indenting the glabrous skin of the distal finger pads with 0.2 and 2mm diameter probes, respectively. Within each of areas 3a, 3b, and 1, activations to mechanical nociceptive stimulation of individual distal finger pads were spatially distinct and somatotopically organized. We observed differential cortical activation patterns. Areas 3a, 3b, and 1 were all activated during mechanical nociceptive stimulation and were modulated by nociceptive stimulus intensity. However, with innocuous tactile stimulation, mainly areas 3b and 1 exhibited response modulation with different levels of stimulation. In summary, mechanical nociceptive inputs are area-specific and topographically represented within SI. We propose that all areas of SI are implicated in encoding the features of mechanical nociception, where areas 3a and 3b are distinctively involved in coding nociceptive and pressure sensation components of stimulation.

Figure 1

Estimations of pain and pressure magnitudes for the 2 different diameter probes. A) Magnitude estimations of pain. Only indentations of 0.2 mm diameter probe with force of 0.3 N or above were judged as painful. Average threshold to elicit a weak pain was about 0.3 N (dashed line). B) Magnitude estimations of pressure. The magnitude estimations of pressure overlapped for the 2 probes: 0.2 mm probe, line of black. 2 mm probe, line of gray. The fitted regression equations are shown on the right. Each symbol (triangle, square, or circle etc) represents the average rating from an individual subject. These observations are consistent with a previous report [23].

Figure 2

An area 3a wide dynamic range unit studied with the 2 and 0.2 mm probes. A) Electrode location centered in area 3a in the region activated by the 0.2 mm probe, as shown for 0.9 N indentation. Dark areas indicate activation. B) PSTH in response to the 2 mm diameter probe indented with 0.3 N. C) PSTH in response to the 0.2 mm diameter probe indented with 0.3 N. and 0.6 N. Lines beneath PSTHs indicate duration of stimulus. Sum of 20 trials. Note that the unit responded to both low pressure and moderate nociceptive stimulation.

Figure 3

Optical signal development and temporal profile of the optical signal in SI to nociceptive and innocuous stimuli. Twelve seconds of the temporal development of optical signal observed in the optical maps in areas 3a, 3b and 1 are shown starting before and continuing after the offset of stimulation for stimulation with the 0.2 mm dia (A) or 2 mm probe indentation at 0.6N, and (C) no stimulation. Black arrows indicate points of interest (see text). (D-F). Timecourses of the optical signals taken from regions of interest in areas 3a, 3b and 1 (boxes in the last images of C). Black and gray curves represent changes of light reflectance (-dR/R %) for the three conditions: 0.6N sharp probe (solid black lines), 0.6N dull probe (solid gray lines), and no stimulus (dotted gray lines)).

Figure 4

Topography of response to a mechanical nociceptive stimulus in areas 3a, 3b and 1. Case 1. Left A-E) Presentation of sharp probe on D5 (A, B) and D3 (C, D) evoked 1-1.5 mm activations in areas 3a, 3b and 1. Activation areas are outlined in red (B) and blue (D). E) Activation areas superimposed on the blood vessel map show topographic organizations in areas 3a, 3b and 1. Case 2. Right A-E) Response to the sharp probe indented on digits, D4 (A, B) and D3 (C, D), activation outlines in B and D. E) Superimposition of activation areas on the blood vessel map show topographic organization. Dots: electrophysiological recording sites; labels indicate digit location (d1-d5) of receptive fields. Dashed lines: approximate borders between areas 3a, 3b, and 1. m = medial, a = anterior.

Figure 5

Different activation patterns were evoked with pressure and the sharp nociceptive probe in SI. Case 1. Moderate (0.6 N) indentations of the 0.2 (nociceptive) and 2 mm (pressure) diameter probes were presented to the D3 distal fingerpad. A-D) Single condition maps showing the focal and spatially distinct activations in areas 3a, 3b and 1 in response to the nociceptive stimulus (A, B) and pressure stimulus (C, D). Activation areas are outlined in blue (B) and red (D). E and F: Subtraction maps (sharp minus dull). C, D) regions exhibiting preferential activation to the sharp probe are outlined in green (F). Nociceptive stimulation produced activation in areas 3a, 3b and 1, whereas pressure elicited activation only in areas 3b and 1. Images were summed over 30 trials. Scale bar = 1 mm. M = medial, p = posterior. Red dotted lines: approximate borders between Areas 3a, 3b, and 1 were determined from the neuronal response properties obtained from electrode mapping SI in this animal.

Figure 6

Cortical responses to increased intensity of mechanical painful stimuli in areas 3a, 3b and 1. Activations evoked with: (A, B) 0.15 N sharp probe, (C, D) 0.3 N sharp probe, and (E, F) 0.6 N sharp probe, and (G) blank. Activations outlined on left (B, D, F). H) Regions of interest (red boxes) in areas 3a, 3b and 1 indicated on (E) map. Dashed lines in A, C, and E: approximate borders of somatosensory areas. (I) Plot of peak reflectance change with indentation force (sharp probe 0.6N: moderately nociceptive; 0.3N: weakly nociceptive, and 0.15 N sharp probe: weak pressure) for areas 3a (blue), 3b(pink) and 1(aqua blue). Scale bar: 1mm.

Figure 7

Cortical responses to increased intensity of pressure stimuli in areas 3a, 3b and 1. Case 3. Activations evoked with: (A, B) 0.6 N pressure stimulus, (C, D) 0.9 N pressure, and (E) no stimulus blank (sum of 30 trials). Activations outlined on left (B, D). F) Regions of interest (red boxes) and electrode penetrations (small circles) superimposed on the blood vessel map. G) Peak change in reflectance signal (mean +/- se) in areas 3a, 3b and 1 to 0.6 N pressure (moderate, green columns), 0.9 N (strong pressure, red columns) and blank (gray columns) in areas 3a, 3b and 1. Dashed lines: approximate borders of areas 3a, 3b and 1. Scale bar: 1mm. m: middle, p: posterior.

Figure 8

Comparison of activation amplitudes for various intensities of indentation of the 0.2 and 2 mm diameter probes. A, B) show peak responses to 5 indentation forces with the 0.2 mm diameter probe (A) and 4 indentation forces with the 2 mm in diameter probe (B) in areas 3a (dashed line), 3b (solid) and 1 (dotted). Arrow in A indicates pain threshold. Note the sharp increase in activation with stimulation above 0.3 N. C and D) Amplitude of responses evoked by stimulus intensities above 0.3 N (middle columns) or below 0.3 N (left columns) and blank (right columns) for the 0.2 mm probe (C) and the 2 mm dia probe (D). Note: Below 0.3 N 0.2 mm probe does note evoke pain sensations. * and lines indicate group comparisons, p<0.05. E) Peak amplitudes evoked by the 0.2 mm probe (left columns) and 2 mm probe (right columns) averaged over the 4 common intensities. Error lines indicate standard errors.