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Serotonergic modulation of pain and analgesic responses: A study in rats with constitutionally altered serotonin transporters
Author(s) -
Kesic M.,
Tvrdeic A.,
Kolaric D.,
Stojkovic R.,
CicinSain L.
Publication year - 2015
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.574
Subject(s) - serotonergic , analgesic , serotonin , serotonin transporter , pharmacology , medicine , receptor
Background A role of the serotonin (5 HT ) 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 the activity of the serotonin transporter, and 5 HT homeostasis in general, on the modulation on pain sensitivity and analgesic responses to drugs that utilize 5 HT mechanisms. Methods A novel genetic animal model, W istar‐ Z agreb 5 HT 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‐5 HT and low‐5 HT , differ in both central and peripheral serotonin homeostasis. Thermal pain sensitivity of 5 HT sublines was assessed at baseline and following administration of analgesic drugs, as determined by paw withdrawal latency to radiant heat stimulation. Results Animals from 5 HT sublines show differences in both basal pain sensitivity and analgesic responses. Rats with the low‐5 HT phenotype displayed decreased baseline paw withdrawal latencies (hyperalgesia) in comparison to their high‐5 HT 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, whereas administration of fluvoxamine did not produce an analgesic effect in either 5 HT subline. Conclusions 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 W istar‐ Z agreb 5 HT rats, with constitutionally up‐regulated/down‐regulated serotonin transporter, as a potential new genetic model for studying serotonergic modulation of pain responses.