Midbrain control of spinal neuronal responses to cold

J Lianne Leith, Stella Koutsikou, Richard Apps, Bridget Lumb. University of Bristol, Bristol, United Kingdom.

Peripheral mechanisms of cool and cold somatosensation in both acute and pathophysiological pain states have received much recent interest. However, information about the central processing of cool and cold-evoked responses is lacking, particularly whether these responses may be modulated by descending control systems that have profound effects on the processing of other sensory modalities. The current study aimed to further investigate the responses of spinal dorsal horn neurones to cool and cold stimuli in the rat, and to determine whether their activity may be modulated by the PAG, which is an important source of descending control.

Extracellular recordings were made from lumbar dorsal horn neurones with receptive fields on the hind limb in alphaxalone-anaesthetised adult male Wistar rats. Cells were characterised according to their responses to low (brush, tap) and high (pinch) threshold mechanical stimulation applied to the receptive field of the cell and classified as class 1 (low threshold), class 2 (wide dynamic range) and class 3 (nociceptive-specific; Menetrey et al, 1977). Cells were then tested for responsiveness to thermal stimuli: acetone (‘cool’), ethyl chloride (‘cold’; both 1ml topically) and noxious heat (55°C water). For cells that responded to acetone and/or ethyl chloride, the effects of activation of the ventrolateral (VL)-PAG were tested. After 3 control responses to acetone or ethyl chloride (applied at 5min intervals), 60-80nl of D,L-homocysteic acid (DLH; 50mM in physiological saline saturated with pontamine sky blue dye to mark injection sites) was pressure injected under stereotaxic guidance into the VL-PAG. Test responses to acetone or ethyl chloride were measured 10s after DLH injection and 3 further recovery responses to acetone or ethyl chloride were measured at 5 min intervals.

Of the recorded units, the majority of class 1 and 2 cells responded to both acetone and ethyl chloride (80 & 85% respectively). In contrast, only approximately half of class 3 cells responded to acetone/ethyl chloride (55%). Descending control from the VL-PAG produced differential effects on responses to acetone and ethyl chloride. In class 1 cells, responses to both acetone and ethyl chloride remained unaltered after VL-PAG stimulation. In class 2 cells, responses to ethyl chloride were significantly depressed by VL-PAG stimulation, whereas responses to acetone were unaltered. In class 3 cells, responses to ethyl chloride were significantly depressed by VL-PAG stimulation.

The data demonstrate that cold-evoked responses in class 2 and 3 dorsal horn neurones, like other sensory modalities, can be modulated by descending control systems that originate in the PAG, and suggest that this control is selective for noxious versus innocuous stimuli.

Menetrey et al (1977) Exp Brain Res 27(1):15-33.