Effect of Serotonin depletion and chemically-induced inflammation on nociceptive behavior and expression of 5-HT[subscript 2A] receptor in rat central nervous system

Abstract

Background – Serotonin (5-HT) is important neurotransmitters in pain pathway. This transmitter modulates pain perception via its diversity of receptor. 5-HT₂ receptor has controversial roles in pain modulation. Its role in nociceptive behavior and cortical activity are still unclear. Objectives- The proposed study aims at investigating (1) the role of 5-HT₂ receptor in chronic pain model as well as the development of chronic pain state (2) the effect of 5-HT depletion on the changes of pain sensation including role 5-HT₂ receptor as well. Methods – This study separated into 2 parts. The First experiment male Wistar rats were divided into inflammation and control group (25 rats each) The inflammation was induced by subcutaneous injection of complete Freund’s Adjuvant (CFA, 0.05 ml) or saline into rats’ right hind paw. After injection both groups were subdivided into 5 subgroups each (n=5) Rats were observed their behaviors at 0 hour 1,3,5 and 7 days Then were evaluated thermal hyperalgesia by paw withdrawal test. After that rats were sacrificed and brains were removed for Fos immunohistochemical study. The day-3 group was selected to study the effect of ketanserin a 5-HT₂ receptor antagonist Ketanserin (0.3 mg/kg body-weight) was i.p administered l hour prior to a 30-minute video recording the study their behavior Four hours after the first injection ketanserin was administered again to study its effect on thermal hyperalgesia Rats were sacrificed for Fos immunohistochemical study The second experiment, male Wistar rats were divided into 5-HT depletion and control group (25 rats each ) The 5-HT depleted state was induced by i.p injection of para-chlorophenylalanie (PCPA) 100 mg/kg body-weight Three days after rats were subcutaneous injection of saline into rats right hind paw Then subdivided ir.to 5 subgroups each (n=5) After that rats were evaluated by 3 procedures as in the first experiment The role of 5-HT2A was perfomed by using ketanserin same as in the first experiment.