Pain may be present at secondary sites in arthritis, e.g. the contralateral limb; this is termed secondary hypersensitivity. In inflammatory arthritis, contralateral peripheral neurons fire antidromically1, suggestive of contralateral spinal neuronal activation2. This contralateral neuronal activation is hypothesised to be a protective mechanism, priming the organism for an immediate inflammatory or pain response should the contralateral limb be damaged2, 3. In this study, we tested the hypothesis that noxious stimulation of the ipsilateral hindpaw in knee joint arthritic rats results in greater activation of contralateral spinal neurons than in naïve rats, using Fos-like immunoreactivity (FLI) to identify activated spinal neurons4. Inflammatory arthritis was induced in male Wistar rats (250-300g, n=17) under isofluorane anaesthesia (2% in O2) by intra-articular injection of 100µl Freund’s complete adjuvant. Controls were naïve (n=14). After 7 days arthritic and naïve rats were anaesthetised (isofluorane induction, followed by i.v. alphaxolone infusion 25mg/kg/h), and A- or C-nociceptors were selectively stimulated in the hindpaw with a contact heat ramp stimulus5. Rats were left for 2 hours for development of Fos, overdosed with alphaxalone and perfuse fixed with 4% paraformaldehyde. After cryoprotection, 50-100 spinal cord sections from L3-L5 were processed for FLI. The 10 sections in which FLI was highest were previously identified, data on the ipsilateral FLI-positive neurons has been published4. Here, FLI-positive neurons were counted in contralateral dorsal horns from naïve (n=5), naïve + A-nociceptor stimulated (4), naïve + C-nociceptor stimulated (5), arthritic (6), arthritic + A-noci stim (5) and arthritic + C-noci stim rats (6). There was a significantly greater number of FLI-positive neurons only in lamina II of arthritic rats when C-nociceptors were stimulated compared to the same stimulation in naïve rats (18±6 neurons compared to 6±1.4, mean±SEM p<0.05 Holm-Sidak). There were no significant changes in any other laminae or when A-nociceptors were stimulated. There was no difference in number of FLI-positive neurons in the contralateral dorsal horn between control (naïve) rats and arthritic rats. Stimulation of one hindpaw significantly increased the number of FLI-positive neurons in the contralateral dorsal horn in naïve (2 way ANOVA, effect of stimulation F(2,55)=12.61, p<0.0001; effect of lamina F(4,55)=8.872, p<0.0001, interaction p=0.13), and arthritic rats (2 way ANOVA, effect of stimulation F(2,70)=7.751, p=0.0009; effect of lamina F(4,70)=5.231, p=0.001, interaction p=0.14). There is greater contralateral activation of lamina II spinal dorsal horn neurons when C-nociceptors are stimulated at secondary sites in arthritic rats compared to naïve rats.