Area 3a Neuron Response to Skin Nociceptor Afferent Drive

Abstract

Area 3a neurons are identified that respond weakly or not at all to skin contact with a 25-38 degrees C probe, but vigorously to skin contact with the probe at > or =49 degrees C. Maximal rate of spike firing associated with 1- to 7-s contact at > or =49 degrees C occurs 1-2 s after probe removal from the skin. The activity evoked by 5-s contact with the probe at 51 degrees C remains above-background for approximately 20 s after probe retraction. After 1-s contact at 55-56 degrees C activity remains above-background for approximately 4 s. Magnitude of spike firing associated with 5-s contact increases linearly as probe temperature is increased from 49-51 degrees C. Intradermal capsaicin injection elicits a larger (approximately 2.5x) and longer-lasting (100x) increase in area 3a neuron firing rate than 5-s contact at 51 degrees C. Area 3a neurons exhibit enhanced or novel responsivity to 25-38 degrees C contact for a prolonged time after intradermal injection of capsaicin or alpha, beta methylene adenosine triphosphate. Their 1) delayed and persisting increase in spike firing in response to contact at > or =49 degrees C, 2) vigorous and prolonged response to intradermal capsaicin, and 3) enhanced and frequently novel response to 25-38 degrees C contact following intradermal algogen injection or noxious skin heating suggest that the area 3a neurons identified in this study contribute to second pain and mechanical hyperalgesia/allodynia.

Dipole source analyses of laser evoked potentials obtained from subdural grid recordings from primary somatic sensory cortex

“…Nociceptive heating (52°C) led to a change in optic signal in area 3A that was larger than that in response to 37°C, while the signal in areas 3B and 1 was smaller (Tommerdahl et al 1996). Strong evidence for the involvement of area 3A in nociceptive processing comes from a recent study by the same group (Whitsel et al 2009). In this study, 3A neuronal firing in monkeys significantly increased when temperatures in the nociceptive range were applied to the neuronal receptive field to innocuous mechanical stimuli.…”

“…This question has also been addressed by studies of S1 using single neuron activity and intrinsic optical signals in anesthetized monkeys (Kenshalo and Willis 1991;Tommerdahl et al 1996;Whitsel et al 1999Whitsel et al , 2009). These studies suggest that nociceptive heat stimuli may result in the activation of subdivisions of S1 including Brodmann area 3A in the depths of the central sulcus (Tommerdahl et al 1996), area 1 at the crown of the postcentral gyrus, or the border zone between Brodmann areas 1 and 3B in the posterior wall of the central sulcus (Kenshalo and Isensee 1983).…”

Nociceptive Steady-State Evoked Potentials Elicited by Rapid Periodic Thermal Stimulation of Cutaneous Nociceptors

“…Another interpretation is that, whereas innocuous vibrotactile input projects predominantly to area 3b and area 1 of S1, nociceptive input may project predominantly to a different area of S1, whose activation may not translate into a measurable SS-EP. In support of this second interpretation, a recent study has shown that, whereas area 3b and area 1 contain very few nociceptive neurons, area 3a is densely populated by neurons responding vigorously to nociceptive stimulation (Whitsel et al, 2009). However, one should then explain why stimulus-triggered neuronal activity originating from a different area of S1 does not generate a scalp SS-EP.…”

Unmasking the obligatory components of nociceptive event-related brain potentials

“…However, unlike the response to nonnociceptive vibro-tactile input, the S1 responses to nociceptive input do not show phase reversal across the central sulcus. This suggests that, as in monkeys (Kenshalo et al 2000;Tommerdahl et al 1996;Vierck et al 2013;Whitsel et al 2009), the S1 activity triggered by nociceptive input does not originate from a population of neurons whose orientation is predominantly anterior-posterior relative to the scalp surface (such as neurons in area 3b of the S1 cortex) and, instead, originates from a population of neurons whose orientation is largely radial to the scalp surface, such as neurons in area 3a and/or 1 of the S1 cortex.…”

“…For example, studies performed with single-cell electrophysiology and optical neuroimaging have shown that in monkeys nonnociceptive tactile input is strongly represented in area 3b of the S1 cortex whereas nociceptive inputs are more strongly represented outside area 3b, such as in area 3a and/or area 1 of the S1 cortex (Kenshalo et al 2000;Tommerdahl et al 1996;Vierck et al 2013;Whitsel et al 2009). Furthermore, there is also evidence suggesting that an important difference between the thalamo-cortical projections of nociceptive and nonnociceptive somatosensory inputs in monkeys is that S1 is a main target for nonnociceptive somatosensory input but not for nociceptive somatosensory input.…”