Serotonergic modulation of pain and analgesic responses : a study in rats with constitutionally altered serotonin transporters

Kesić, Maja; Tvrdeić, Ante; Kolarić, Darko; Stojković, Ranko; Čičin-Šain, Lipa (2015) Serotonergic modulation of pain and analgesic responses : a study in rats with constitutionally altered serotonin transporters. European journal of pain, 19 (4). pp. 508-515. ISSN 1090-3801

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Abstract

A role of the serotonin (5HT) transporter, a key regulator of serotonergic transmission, in the physiology, pharmacology and genetics of pain responses has been proposed recently. The present study aimed to explore the impact of constitutive differences in activity of the serotonin transporter, and 5HT homeostasis in general, on the modulation on pain sensitivity and analgesic responses to drugs that utilize 5HT mechanisms. A novel genetic animal model, Wistar- Zagreb 5HT rats, obtained by selective breeding of animals for extreme activity of the platelet serotonin transporter was used. As a consequence of breeding, two sublines of this model, termed high-5HT and low-5HT, differ in both central and peripheral serotonin homeostasis. Thermal pain sensitivity of 5HT-sublines was assessed at baseline and following administration of analgesic drugs, as determined by paw withdrawal latency to radiant heat stimulation. Animals from 5HT-sublines show differences in both basal pain sensitivity and analgesic responses. Rats with the low-5HT phenotype displayed decreased baseline paw withdrawal latencies (hyperalgesia) in comparison to their high-5HT counterpart (25%, p<0.001). They also showed better analgesic response to acute and prolonged treatment with tramadol (p=0.027) and clomipramine (p=0.019), respectively, while administration of fluvoxamine did not produce an analgesic effect in either 5HT-subline. These findings support the idea that functionality of the serotonin transporter is one of the physiological/genetic determinants of individual differences in pain responses and modulation. They also validate Wistar-Zagreb 5HT rats, with constitutionally upregulated/downregulated serotonin transporter, as a potential new genetic model for studying serotonergic modulation of pain responses.

Item Type:	Article
Uncontrolled Keywords:	serotonin; 5HTT; pain; analgesia; animal model; antidepressants
Subjects:	BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Neuroscience
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Serotonergična neurotransmisija: geni, proteini i ponašanje- Jasminka Štefulj 098-1081870-2395 MZOS Serotonergični mehanizmi u alkoholizmu- Lipa Čičin-Šain 098-1081870-2397 MZOS
Depositing User:	Maja Kesić
Date Deposited:	03 Apr 2023 13:01
URI:	http://fulir.irb.hr/id/eprint/7799
DOI:	10.1002/ejp.574

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