Sertraline inhibits formalin-induced nociception and cardiovascular responses

The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT) levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g) were divided into 4 groups (N = 8 per group): sertraline-treated group (Sert + Saline (Sal) and Sert + Formalin (Form); 3 mg.kg(-1).day(-1), ip, for 7 days) and saline-treated group (Sal + Sal and Sal + Form). The rats were injected with 5% (50 mu L) formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency), assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 +/- 14.7%), mean arterial pressure (+1.4 +/- 3 mmHg), heart rate (+13 +/- 6.8 bpm), respiratory frequency (+4.6 +/- 5 cpm) and serum 5-HT increased to 1162 +/- 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 +/- 6.9%, -3.3 +/- 2 mmHg, -13.1 +/- 10.8 bpm, -9.8 +/- 5.7 cpm) and serum 5-HT level dropped to 634 +/- 69 ng/mL (P < 0.05). These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism.