Descending controls on spinal nociception, particularly descending facilitatory pathways from the midbrain periaqueductal grey (PAG), play major roles in the initiation and maintenance of chronic pain, and are important determinants of the pain experience. A better understanding of these systems may inform the development of more effective chronic pain treatments. Prostaglandin receptors EP1-4 in the ventrolateral periaqueductal grey (vlPAG)1 contribute to acute inflammatory pain and in nerve injury vlPAG EP1 receptors contribute to tonic descending facilitation in naïve and injured rats2. Inflammatory arthritis was induced in male rats under brief isoflurane anaesthesia (2% in O2) by left knee intra-articular injection of Freund’s complete adjuvant (100µl/1mg.ml-1). Naïve animals were used as controls. After 7 days, rats were re-anesthetised with halothane (3% in O2) and maintained on alfaxan infusion (i.v. 25mg.kg.h 1). Bipolar steel wire electrodes were placed in the bicep femoris of the left hind limb to record electromyographic activity, and a micropipette positioned stereotaxically in the left PAG. A and C nociceptors were preferentially activated by application of fast (7.5°C.s-1) or slow (2.5°C.s-1) rates of contact skin heating applied to the dorsal surface of the left hind-paw3 respectively. Withdrawal thresholds to A- and C-nociceptor stimulation (interstimulus interval 8 min) were determined before and after delivery of drug/vehicle into the PAG by pressure ejection. There was a prolonged secondary (hindpaw) hyperalgesia 7 days after induction of inflammation, indicated by a reduction in A- but not C-nociceptor withdrawal thresholds (naïve vs. arthritic A-nociceptor thresholds: 57±1oC vs 54±1.2oC . p<0.0001 unpaired t test. n=16 naïve, 18 arthritic). In naïve animals EP3 receptor antagonism (GW671021B 250nM/200nl) in the vlPAG increased C- but not A-nociceptor evoked-reflexes. In contrast in secondary hyperalgesia, EP3 receptor antagonist increased A-nociceptor responses (AUC GW A-nociceptor effect vs AUC Vehicle A-nociceptor effect: 352.1±85.0oC.min vs 116.8±26.10oC.min. p<0.0357 Mann Whitney. n=5 for GW, n=3 for Vehicle.) with minimal effect on C-nociceptor reflexes. Inflammatory knee joint arthritis produces secondary hyperalgesia of the hind paw involving sensitisation of A- but not C-nociceptor-evoked spinal reflexes. Blockade of prostaglandin EP3 receptors in the vlPAG predominantly modulates A-nociceptor withdrawals in the hyperalgesic state but selectively alters C-nociceptor reflexes in the normal rat. In the transition to chronic inflammatory pain, descending EP3 receptor-mediated facilitation from vlPAG switches from C-nociceptor facilitation in naïve rats to A-nociceptor facilitation in inflammatory secondary hyperalgesia.