الفهرس 
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Abstract
Background: Clinical observations recognized the co-existence and interactions of pain and depression a long time ago.
Aim: The aim of the present study was to investigate the effect of BCG-induced depression on formalin-induced pain related behaviour and on planter incision-induced mechanical allodynia, in Swiss albino mice. The effect of fluoxetine and ibuprofen on both pain behaviours were also studied. Finally, brain and spinal levels of NO, eNOS and PGE2 were estimated.
Methods and results: BCG induced a depressive behaviour that was seen in the FST and the TST. It also induced a decrease in pain-related behaviour in the formalin test, and an increase in the baseline of the 60% mechanical threshold compared to the control group in von Frey mechanical allodynia test. Fluoxetine (80 mg/L of drinking water) showed a significant decrease in the immobility time in the FST and TST and enhanced pain related behaviour in formalin test in the BCG-inoculated group. However, it did not affect the increase in the pain threshold in the planter incision allodynia model. Adding ibuprofen to drinking water (0.2 g/L of drinking water), reversed the depressive like behaviour induced by BCG and enhanced pain-related behaviour in formalin test, in both the total pain-related behaviour and phase 2. It also prevented the increase in the base line induced by BCG. On the other hand, the incisional pain model was not affected by BCG inoculation except at the 2-hour time point, where it showed hypoalgesia, as well. BCG increased cerebral NO, planter incision however, reduced NO in BCG inoculated mice. BCG also increased spinal NO level after incision, compared to the saline treated group. Both BCG and planter incision decreased cerebral eNOS level. However, when planter incision was performed in BCG inoculated mice, there was no difference compared to the BCG control group. Planter incision also decreased cerebral PGE2 level. However, when planter incision was performed in BCG inoculated mice, there was no difference compared to the BCG control group.
Conclusion: the model of chronic immune activation and depressive like behaviour induced by BCG inoculation resulted in hypoalgesia in formalin test that was reversed by fluoxetine and ibuprofen. It also resulted in an increase in mechanical threshold to Von Frey filaments, which was partially reversed by ibuprofen but not fluoxetine. NO and PGE2 may have a role in this altered pain sensation.