Introduction
The neutrophil to lymphocyte ratio (NLR) is an easily calculated, systemic inflammation-based parameter. The NLR correlation with inflammatory, neo-plastic, and cardiovascular diseases has been evaluated in various studies. In a number of studies, the NLR has been suggested as a marker of acute pancreatitis prognosis. However, there are limited number of studies investigating the correlation between NLR and chronic inflammatory pain responses. In this study, we investigated the changes of NLR following Freund\'s Complete Adjuvant (CFA) injection in mice and the antinociceptive or anti-inflammatory effect of Nefopam and Indomethacin.

Methods
Male ICR mouse (20-25g) was used. CFA 10 μl was injected subcutaneously into the plantar surface of the left hind paw. Their nocifensive behaviors were observed at the POD 1, 2, 3, 5, and 7 day time points. Behavior tests were conducted at 1, 2, 3, 5, and 7 day after administration of CFA. Tactile threshold was measured by applying a von Frey filament to the midplantar surface of the left hindpaw until a positive sign for pain behaviour was elicited. A series of eight calibrated fine von Frey filaments (0.07, 0.16, 0.4, 0.6, 1.0, 1.4, 2.0, 4.0 g) was presented serially to the lesioned hindpaw in ascending order of strength with sufficient force to cause slight bending against the paw where it was held for six seconds. A brisk withdrawal or paw flinching was considered a positive response, in which case the next filament tested was the next lower force. In the absence of such response, the next filament tested was the next greater force. In the absence of a response at 15 g pressure, the animal was assigned this cutoff value. The tactile stimulus producing a 50% likelihood of withdrawal was determined by using the up-down method. Saline 0.1 ml, Nefopam 20 mg/kg, and Indomethacin 10 mg/kg were intraperitoneally administered 30 minutes before CFA administration (n = 7). 1, 2, 3, 5, and 7 days after CFA administration, blood was drawn from the heart under sevoflurane anaesthesia for the analysis of the NLR. Total leukocyte counts and the NLR were estimated using automatic hemocytometer. The results were expressed as number of cells × 103/μl.

Results
In each group, the mechanical allodynia was produced and it progressively decreased as time passed. In the pretreatment groups (Nefopam and Indomethacin) the paw withdrawal threshold was significantly higher compared to the saline group. The NLR was increased 1 and 2day after CFA administration. After then progressively decreased. Intraperitoneally administered Nefopam 20 mg/kg significantly attenuated the NLR after 2 day. However, the NLR was not significantly affected by indomethacin.

Conclusions
The Neutrophil to Lymphocyte ratio could be used as an marker of chronic imflammatory pain. It needs further evaluation