Previous work from our laboratory has studied the functional roles of distinct types of nociceptors in acute pain processing [1, 2]. We have demonstrated that descending control can differentially modulate A- vs C-fibre evoked responses and we have shown that thermal nociception is under tonic regulation by descending noradrenergic control [3]. However, the different roles these nociceptors have in the development of heat hyperalgesia during chronic pain states and the changes descending control are poorly understood. Here we have investigated the descending noradrenergic control of A- and C-heat nociceptor evoked responses during the development of neuropathic hyperalgesia. Wistar rats (300-350g) had tibial nerve transection (TNT) under ketamine (50mg/kg) and medetomidine (300µg/kg) recovery anaesthesia [4]. Subsequently heat ramp withdrawal experiments were performed at day 3-5 or day 19-21 post-TNT under alphaxalone (9 – 15mg.kg-1.h-1 i.v.) anaesthesia. Fast (7.5°C/s) or slow (2.5°C/s) rates of skin heating were applied to the dorsal hindpaw to preferentially activate A- or C-heat nociceptors, respectively. EMG withdrawal response thresholds were recorded from the biceps femoris. A 32 gauge intrathecal catheter was inserted at the L5-L6 interspace for administration of yohimbine (α2-AR antagonist, 30μg) or clonidine (α2-AR agonist, 15μg). Changes in dopamine-beta-hydroxyalse (DBH) immunoreactivity were analysed at days 19-21. Data are expressed as mean withdrawal thresholds ± SEM or %DBH immunoreactivity analysed using either t-test or one-way ANOVA with Bonferroni’s post tests. Following TNT animals showed substantial A- but not C-fibre evoked ipsilateral hyperalgesia by day 21 (TNT: A-fibre: day 3 55.2±0.7°C vs day 21 47.8±0.9°C P<0.001 n=5) when compared to sham. Intrathecal yohimbine revealed sensitivity of A- but not C-fibre evoked responses at day 3 (control 55.2±0.7°C vs 51.6±0.6°C post yohimbine P<0.001 n=4). Once hyperalgesia had developed (by day 19) yohimbine had no further sensitising effect on A-fibre responses however intrathecal clonidine increased A-fibre thresholds to beyond cut off (>58°C, P<0.01, n=3). Yohimbine was without effect in sham animals (n=3). Interestingly, yohimbine revealed contralateral heat hypersensitivity mediated by A- but not C-fibres at days 19-21 (A-fibre: 54.6±0.8°C to 49.0±0.8°C P<0.01, n=5). By days 19-21 there was a loss of DBH-ir in the ipsilateral L4-L6 spinal cord when compared to sham (n=3).These data demonstrate that descending pontospinal noradrenergic tone preferentially modulates, both temporally and spatially, the development of fast, prickling, heat hypersensitivity mediated by A-fibres following a loss of descending noradrenergic innervation to the lumbar region.