Proceedings of The Physiological Society
Cardiff University (2009) Proc Physiol Soc 17, C15
Midbrain control of spinal cold processing
J. Leith1, S. Koutsikou1, B. M. Lumb1, R. Apps1
1. Department of Physiology & Pharmacology, University of Bristol, Bristol, United Kingdom.
Peripheral mechanisms of cold somatosensation in normal and pathophysiological states have received much recent interest. However, information about the central processing of cold sensory input is lacking, particularly whether these inputs may be modulated by descending control systems that have profound effects on the processing of other sensory modalities. This study characterised spinal responses to low and high intensity cold stimuli and established the extent to which they are modulated by descending control from the periaqueductal grey (PAG), a major determinant of acute and chronic pain. In alphaxalone-anaesthetised (Alfaxan; 15-30mg.kg-1.hr-1, i.v.) male Wistar rats (280-300g) either paw withdrawal reflexes (measured as EMG activity from biceps femoris; n=5) or extracellular neuronal activity from lumbar spinal dorsal horn neurones (32 cells, from n=19) was recorded in response to hindpaw cooling with acetone and ethyl chloride (both 1ml topically). Ethyl chloride, but not acetone, produced sufficiently noxious cold to evoke withdrawal reflexes in lightly anaesthetised rats, which were significantly depressed (p<0.01, ANOVA) by chemical stimulation of the ventrolateral (VL)-PAG with D,L-homocysteic acid (DLH, 80nl, 50mM in physiological saline saturated with pontamine sky blue dye to mark injection sites). Dorsal horn neurones were characterised according to their responses to low (brush, tap) and high (pinch) threshold mechanical stimulation applied to the receptive field 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 thermal responses with acetone, ethyl chloride and noxious heat. The majority of class 1 and 2 cells responded to both acetone and ethyl chloride (66 & 85% respectively), in contrast to only around half (55%) of class 3 cells. The effects of VL-PAG stimulation were tested in cold responsive cells, which produced differential effects on cold responses dependent on cell type and stimulus intensity. All cold-evoked activity in non-nociceptive class 1 cells and innocuous cold (acetone) responses of class 2 neurones remained unaltered (n=3-6; all p>0.05, ANOVA). In contrast, noxious cold (ethyl chloride) responses of class 2 neurones and all cold-evoked activity in nociceptive-specific class 3 neurones were significantly depressed (n=3-7; all p<0.01, ANOVA). The data demonstrate that spinal responses to noxious cold can be powerfully modulated by descending control systems originating in the PAG, and suggests that this control is selective for noxious versus innocuous stimulus intensities.
Where applicable, experiments conform with Society ethical requirements