Spinal dorsal horn neuronal responses to myelinated versus unmyelinated heat nociceptors and their modulation by activation of the periaqueductal grey in the rat

Abstract

The aim of this study was to further understand the central processing of inputs arising from unmyelinated and myelinated nociceptors by (i) determining the response characteristics of Class 2 dorsal horn neurones to preferential activation of C- and A-fibre heat nociceptors, and (ii) investigating the control exerted by the dorsolateral/lateral region of the midbrain periaqueductal grey (DL/L-PAG) on C- and A-fibre-evoked responses of these neurones. The use of different rates of skin heating to preferentially activate unmyelinated (C-fibre; 2.5 degrees C s(-1)) versus myelinated (A-fibre; 7.5 degrees C s(-1)) heat nociceptors revealed that, in response to C-nociceptor activation, Class 2 neurones encode well only over the first 5 degrees C above threshold, and that at higher temperatures responses decline. In contrast, responses to A-nociceptor activation are linear and encode skin temperature over more than 10 degrees C, and almost certainly into the tissue-damaging range. PAG stimulation raised thresholds and decreased significantly the magnitude of responses to A- and C-nociceptor activation. However, differences were revealed in the effects of descending control on the relationships between skin temperature and neuronal firing rate; the linear relationship that occurred over the first 5 degrees C of slow rates of skin heating was no longer evident, whereas that to fast rates of skin heating was maintained over the entire range, albeit shifted to the right. These data indicate that the sensori-discriminative information conveyed in A-fibre nociceptors is maintained and that the information from C-nociceptors is lost in the presence of descending control from the DL/L-PAG. The data are discussed in relation to the role of the DL/L-PAG in mediating active coping strategies.

Figure 1. Data from an individual Class 2 dorsal horn neurone

A, raster plot to illustrate the response of the neurone to supramaximal electrical stimulation in its cutaneous receptive field at time zero. B, photomicrograph to illustrate the recording site (pontamine sky blue (PSB) deposit) in the dorsal horn. C, response to a fast heating trial. Top trace, average discharge frequency per second. Middle trace, skin temperature. Lower trace, extracellular unit recording. Vertical lines, 1°C bins. Continuous horizontal line, background level of firing which is subtracted from the firing rate to calculate the magnitude of the response (shaded area).

Figure 2. Activation of class 2 dorsal horn neurons by slow and fast rates of skin heating

A and B, firing frequencies (upper traces) and extracellular recordings (middle traces) of an individual neurone to illustrate the relationship between skin temperature (lower traces) and responses evoked by slow (A) and fast (B) rates of skin heating. C, temperature–response relationships of Class 2 neurones to slow (open symbols, n = 11) and fast (filled symbols, n = 12) rates of skin heating; data are means ±s.e.m.; responses to fast rates of heating follow a linear relationship (r²= 0.9), whereas responses to slow rates best fit a bell-shaped function (r²= 0.63); *P < 0.05, **P < 0.01 (two-way Student's t test), statistical significance between responses at any given temperature above threshold (hashed line).

Figure 6. Effect of PAG stimulation on response profiles

Effects of neuronal activation in the periaqueductal grey on the responses of Class 2 neurones to slow (A, n = 11) and fast (B, n = 12) rates of skin heating. Data (means ±s.e.m.) are normalized to threshold responses in the control period.

Figure 3. Midbrain sites at which microinjection of 50 mm dl-homocysteic acid evoked pressor responses

Sections shown are 7.5, 8.0 and 8.72 mm caudal to bregma (redrawn from Paxinos & Watson, 1986). NB, one pressor site that was not confirmed histologically is not included.

Figure 4. Effects of neuronal activation in the PAG on the responses of an individual neurone to slow (A) and fast (B) rates of skin heating

Traces: top, action potential frequency; second, extracellular recording; third, skin temperature; bottom, arterial blood pressure. Arrows indicate the timing of microinjection of DLH (dl-homocysteic acid) in the periaqueductal grey.

Figure 5. Effect of PAG stimulation on response thresholds

Scatterplots illustrating the effect of microinjection of DLH in the periaqueductal grey on thresholds of neuronal responses to slow (A, n = 11) and fast (B, n = 12) heating ramps. *P < 0.05, ***P < 0.001 (two-way ANOVA).