Sertraline inhibits formalin-induced nociception and cardiovascular responses

C.H Santuzzi,W.L.S Gonçalves,G.R Abreu,J.G.P Pires,R.V Tiradentes,H.A Futuro Neto,S.A Gouvea

doi:10.1590/s0100-879x2011007500154

Abstract

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 µL) 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.

Highlights

Several studies in rodents have suggested that serotonin (5-HT) modulates nociceptive responses [1,2,3]
The present study showed that sertraline inhibits a classical experimental model of pain, the formalin-induced nociception
McNamara et al [26] showed that formalin activates primary afferent sensory neurons through a specific and direct action on TRPA1, a member of the transient receptor potential family of cation channels that is highly expressed by a subset of C-fiber nociceptors

Summary

Introduction

Several studies in rodents have suggested that serotonin (5-HT) modulates nociceptive responses [1,2,3]. Its involvement in pain processing is complex since 5-HT may inhibit and/or facilitate nociceptive transmission depending on the type of nociceptive stimuli and the nature of the 5-HT receptors expressed, i.e., peripheral and/or central [3,4]. Peripheral 5-HT2, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors are involved in the sensitization of primary afferent fibers activated by formalin injection [10]. Among these receptor subtypes, 5-HT2A receptors have an important role in inflammatory pain [3,11]. It is reasonable to infer that a surge in neuronal afferent activity after formalin injection, in a nerve ramus that was previously silent, can be due to nociceptive receptor activation

Objectives

Methods

Results

Conclusion