Specific patterns of survival (defence) behaviours that are co-ordinated by the different functional columns of the midbrain periaqueductal grey (PAG) may be triggered by A- and C-nociceptive inputs that have different behavioural significance, in that they mediate ‘first’ and ‘slow’ pain respectively, and have different roles in the initiation and maintenance of chronic pain. It is of considerable importance therefore to determine to the columnar organisation of A- and C-nociceptor inputs in normal animals and in animal models of chronic pain. Our previous studies1,2 have shown that, in uninjured animals, inputs arising from these different fibre types target different regions of the PAG: C-fibre inputs target the ventrolateral column of the PAG (VL-PAG) and A-nociceptor inputs, the dorsolateral/lateral column (DL/L-PAG). This current study was designed to determine the activation of different regions of the PAG following either A- or C-nociceptor stimulation in an area of secondary hyperalgesia in a rat model of inflammatory arthritis. Arthritis was induced by injection of Freund’s Complete Adjuvant into the left knee joint under brief isoflurane/O2 anaesthesia (2% in O2). Animals (4-6/group) were re-anaesthetised 7 days later (halothane (2% in O2), alfaxan maintenance (i.v. 25.mg.kg.h-1) and either C- or A-nociceptors preferentially activated respectively, by slow (2.5°C.s-1, 30-55°C) or fast (7.5°C.s-1, 30-57°C) contact heating of the left hindpaw dorsum (area of secondary hyperalgesia). Some inflamed rats did not receive any stimulation (control group). Two hours after stimulation, animals were perfuse fixed and brains processed immunocytochemically for visualisation of Fos-like immunoreactivity (FLI). Fos-positive PAG neurones were counted (Image J, NIH) and their locations assigned to the different functional columns of the PAG throughout its rostrocaudal extent. FLI was greater in caudal than rostral PAG in stimulated and control animals. Hindpaw A-nociceptor stimulation increased FLI in the caudal right (contralateral) L-PAG but in no other area, in arthritic rats. These results demonstrate that caudal L-PAG activation is greater in response to A-nociceptor input from the area of secondary hyperalgesia than in inflamed unstimulated rats. These data may indicate that processing of ‘first’ pain in L-PAG is enhanced in secondary inflammatory hyperalgesia.