Inflammatory pain treatments frequently lack efficacy and/or exhibit undesirable side effects. Neurokinin 1 receptor expressing (NK1R+) neurons in the lamina I region of the spinal cord are crucial for the manifestation of inflammatory pain [1]. Recent evidence has described an essential role for C-fibre nociceptors in the development of inflammatory pain [2] and it has been established that lamina I NK1R+ neurons predominantly receive monosynaptic C-fibre input [3, 4]. Therefore, identification of drugs which presynaptically modulate C-fibre nociceptive input to these neurons could aid analgesia development. Recent data have shown that chemerin receptor 23 (ChemR23) activation can attenuate inflammatory pain by a mechanism involving inhibition of potentiated spinal cord activity. Interestingly, ChemR23 was found to be expressed by likely C-fibre nociceptors that target lamina I NK1R+ neurons [5]. Therefore, we investigated whether chemerin, the natural ChemR23 ligand, can modulate potentiated C-fibre input to lamina I NK1R+ neurons. Whole-cell patch clamp recordings were made from presumptive NK1R+ neurons, identified following pre-incubation with tetramethylrhodamine conjugated substance P [3, 4], in rat (∼postnatal day 21) spinal cord slices (L4/5), with/without dorsal roots attached. Rats were either untreated (control) or had received an intraplantar injection of complete Freund’s adjuvant (CFA: 0.5mg/ml, 1μl/g body weight, under brief isoflurane anaesthesia) ∼4 days prior. Values are mean±SEM, compared with 2-way ANOVA unless stated otherwise. Miniature EPSCs (mEPSCs) were recorded, in control tissue, in the presence of the transient receptor potential subtype vanilloid 1 agonist capsaicin (1μM) to pharmacologically presynaptically potentiate likely C-fibre nociceptive input. Capsaicin was applied alone (n=12) or in the presence of chemerin (100ng/ml, n=10). Chemerin significantly reduced capsaicin potentiation of mEPSC frequency (capsaicin vs. capsaicin+chemerin: 20.79±5.19 vs. 9.67±2.71Hz, P<0.05, Bonferroni post-test), but was without effect in non-potentiated conditions (baseline vs. chemerin: 1.16±0.25 vs. 1.46±0.54Hz, P=0.824, Wilcoxon, n=11). Monosynaptic C-fibre input to lamina I NK1R+ neurons was identified in control and CFA tissue by dorsal root stimulation [3, 4] and C-fibre evoked EPSCs (eEPSCs) were recorded in the absence (no drug control) or presence of chemerin. In control tissue, chemerin exhibited no effect on C-fibre eEPSC peak amplitude. However, in CFA inflammation tissue chemerin significantly attenuated C-fibre eEPSC peak amplitude in a subset of neurons (P<0.01). Thus, we have novelly shown functional expression of ChemR23 on presynaptic terminals of likely C-fibre nociceptive synapses with lamina I NK1R+ neurons and suggest that activation of these receptors can attenuate C-fibre nociceptive input to these neurons in inflammatory pain.