Selective inhibition from the anterior hypothalamus of C- versus A-fibre mediated spinal nociception.

Modulation of spinal nociception from the anterior hypothalamus/preoptic area (AH/POA), and consequent alterations in the pain experience may contribute to integrated responses brought into play during fear or stress and as part of the sickness response. This study was designed to compare the effects of descending control from AH/POA on A- versus C-fibre-evoked spinal nociception, since any differential control is of behavioural and clinical importance given that A-fibre and C-fibre nociceptors convey different qualities of the pain signal (first and second pain, respectively), and play different roles in the development and maintenance of chronic pain states. In anaesthetised rats, electromyographic responses were recorded to monitor thresholds of withdrawal to slow (2.5 degrees Cs(-1)) or fast (7.5 degrees Cs(-1)) rates of skin heating of the hindpaw, to preferentially activate C- or A-nociceptors, respectively. Neuronal activation by microinjection of dl-homocysteic acid at sites within a specific region of AH/POA, lateral area of the anterior hypothalamus (LAAH), significantly increased response thresholds to slow heating rates (p<0.02, n=11), but not those to fast rates of heating (p=0.48, n=10). Injection of DLH adjacent to LAAH (n=9) had no significant effect on responses to slow (n=8) or fast (n=9) rates of skin heating. The functional significance of differential descending control of spinal processing of C- and A-nociceptive inputs is discussed with respect to roles both of the LAAH in pain processing, and of C- and A-nociceptive inputs in acute and chronic pain.

A reliable method for the preferential activation of C- or A-fibre heat nociceptors.

There is strong evidence that A- and C-fibre nociceptors evoke significantly different sensory experiences, are differentially sensitive to pharmacological intervention, and play different roles in pain pathology. It is therefore of considerable interest to be able to selectively activate one fibre type or the other in studies of nociceptive processing. Here, we report significant modifications to a non-invasive technique, first described by Yeomans et al. [Pain 59 (1994) 85; Pain 68 (1996) 141; Pain 68 (1996) 133], which uses different rates of skin heating to preferentially activate A- or C-nociceptors. A copper disk (diameter: 4mm) was used to transfer heat evenly across the dorsal surface of the rat hindpaw. Initial experiments established the relationship between the temperature at the skin surface and the sub-epidermal temperature. Subsequently, the vanilloid capsaicin, which sensitises unmyelinated C-mechanoheat nociceptors, was shown to decrease the thresholds of reflex responses evoked by slow rates of heating. In contrast thresholds of responses to fast rates of skin heating were unchanged, indicating that nociceptors activated by this stimulus were capsaicin-insensitive A-fibre heat nociceptors.