title: Sertraline inhibits formalin-induced nociception and cardiovascular responses.
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.
authors.affiliation: Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Victória, ES, Brasil. cintiasantuzzi@yahoo.com.br
authors.forename: C H
authors.initials: CH
authors.lastname: Santuzzi
authors.forename: H A
authors.initials: HA
authors.lastname: Futuro Neto
authors.forename: J G P
authors.initials: JG
authors.lastname: Pires
authors.forename: W L S
authors.initials: WL
authors.lastname: Gonçalves
authors.forename: R V
authors.initials: RV
authors.lastname: Tiradentes
authors.forename: S A
authors.initials: SA
authors.lastname: Gouvea
authors.forename: G R
authors.initials: GR
authors.lastname: Abreu
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D005557:Formaldehyde / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects; D059225:Nociception / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D056152:Respiratory Rate / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects; D012701:Serotonin / Q000097:blood; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology*
chemical_list: D005557:Formaldehyde; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
references.citation: Prog Neurobiol. 1999 Jan;57(1):1-164
references.pmid: 9987804
references.citation: Yonsei Med J. 2010 Nov;51(6):960-4
references.pmid: 20879067
references.citation: Pain. 2011 Mar;152(3):687-697
references.pmid: 21239110
references.citation: Eur J Pharmacol. 2011 Apr 25;657(1-3):97-103
references.pmid: 21316357
references.citation: J Lab Clin Med. 2004 Jul;144(1):31-7
references.pmid: 15252405
references.citation: Neuroscience. 2010 Jan 20;165(2):561-8
references.pmid: 19837141
references.citation: Neuroscience. 2006 Sep 1;141(3):1517-24
references.pmid: 16750893
references.citation: Pain. 2006 May;122(1-2):130-6
references.pmid: 16527395
references.citation: J Anesth. 2001;15(3):154-8
references.pmid: 14566514
references.citation: Eur J Pain. 2009 May;13(5):441-7
references.pmid: 18656400
references.citation: Brain Res Bull. 2001 Nov 15;56(5):425-39
references.pmid: 11750788
references.citation: Respir Physiol Neurobiol. 2008 Dec 31;164(3):350-7
references.pmid: 18775520
references.citation: Am J Chin Med. 2006;34(4):565-74
references.pmid: 16883628
references.citation: Respir Physiol Neurobiol. 2008 Dec 10;164(1-2):222-32
references.pmid: 18595785
references.citation: J Pharmacol Exp Ther. 2010 Nov;335(2):497-505
references.pmid: 20675432
references.citation: Exp Physiol. 2005 May;90(3):259-66; discussion 266-9
references.pmid: 15728134
references.citation: Mol Neurobiol. 2004 Oct;30(2):117-25
references.pmid: 15475622
references.citation: Annu Rev Neurosci. 2003;26:239-66
references.pmid: 12598679
references.citation: Neuroscience. 1997 Oct;80(3):939-49
references.pmid: 9276504
references.citation: Pain. 1977 Dec;4(2):161-174
references.pmid: 564014
references.citation: Phytother Res. 2010 Jan;24(1):113-8
references.pmid: 19468987
references.citation: J Membr Biol. 2008 Mar;222(2):79-90
references.pmid: 18418539
references.citation: Pharmacol Biochem Behav. 1992 Jan;41(1):53-6
references.pmid: 1531705
references.citation: Respir Physiol Neurobiol. 2010 Jun 30;172(1-2):42-52
references.pmid: 20399913
references.citation: Eur Neuropsychopharmacol. 2004 Jan;14(1):29-37
references.pmid: 14659984
references.citation: Neuroscience. 2009 Aug 18;162(2):444-52
references.pmid: 19422883
references.citation: Neuroscience. 2001;102(4):937-44
references.pmid: 11182255
references.citation: Neuroscience. 2007 Mar 16;145(2):708-14
references.pmid: 17257768
references.citation: Pharmacol Biochem Behav. 1998 Feb;59(2):331-8
references.pmid: 9476978
references.citation: CNS Drug Rev. 2001 Spring;7(1):25-47
references.pmid: 11420571
references.citation: Pharmacol Res. 2003 Aug;48(2):157-65
references.pmid: 12798668
references.citation: Pain. 2011 Feb;152(2):274-284
references.pmid: 20943317
references.citation: Pain Med. 2000 Dec;1(4):310-6
references.pmid: 15101877
references.citation: Trends Pharmacol Sci. 2008 Sep;29(9):472-81
references.pmid: 19086344
references.citation: J Psychopharmacol. 2010 Dec;24(12):1793-801
references.pmid: 19825902
references.citation: J Neurosci. 2011 Jan 26;31(4):1410-8
references.pmid: 21273425
references.citation: Can J Physiol Pharmacol. 1997 Oct-Nov;75(10-11):1203-11
references.pmid: 9431444
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13525-30
references.pmid: 17686976