The critical role of spinal 5-HT7 receptors in opioid and non-opioid type stress-induced analgesia
Autor: | Emre Karakus, Melik Seyrek, Ahmet Dogrul, Zekai Halici, Serdar Kahraman, Ozgur Yesilyurt, Mehmet Salih Deveci, Serdar Tasdemir |
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Rok vydání: | 2015 |
Předmět: |
Male
medicine.drug_class Receptor expression Pharmacology Serotonergic Mice SB-269970 Phenols medicine Animals RNA Messenger Mice Inbred BALB C Sulfonamides Behavior Animal business.industry Pain Perception Receptor antagonist Spinal cord Lumbar Spinal Cord Nociception medicine.anatomical_structure Opioid Gene Expression Regulation Spinal Cord Anesthesia Receptors Serotonin Receptors Opioid Serotonin Antagonists business Stress Psychological medicine.drug Serotonergic Neurons |
Zdroj: | European journal of pharmacology. 762 |
ISSN: | 1879-0712 |
Popis: | The opioid and non-opioid types of stress-induced analgesia have been well defined. One of the non-opioid type involve the endocannabinoid system. We previously reported that the spinal serotonin 7 receptor (5-HT7) blockers inhibit both morphine and cannabinoid-induced analgesia, thus we hypothesized that descending serotonergic pathways-spinal 5-HT7 receptor loop might contribute to stress-induced analgesia. Stress-induced analgesia was induced with warm (32°C) or cold (20°C) water swim stress in male Balb-C mice. The effects of intrathecal injection of a selective 5-HT7 receptor antagonist, SB 269970, of the denervation of serotonergic neurons by intrathecal administration of 5,7-dihydroxytryptamine (5,7-DHT) and of lesions of the dorsolateral funiculus on opioid and non-opioid type stress-induced analgesia were evaluated with the tail-flick and hot plate tests. The expression of 5-HT7 receptors mRNA in the dorsal lumbar region of spinal cord were analyzed by RT-PCR following spinal serotonin depletion or dorsolateral funiculus lesion. The effects of the selective 5-HT7 receptor agonists LP 44 and AS 19 were tested on nociception. Intrathecal SB 269970 blocked both opioid and non-opioid type stress-induced analgesia. Dorsolateral funiculus lesion or denervation of the spinal serotonergic neurons resulted in a marked decrease in 5-HT7 receptor expression in the dorsal lumbar spinal cord, accompanied by inhibition of opioid and non-opioid type stress-induced analgesia. However, the systemic or intrathecal LP 44 and AS 19 alone did not produce analgesia in unstressed mice. These results indicate that descending serotonergic pathways and the spinal 5-HT7 receptor loop play a crucial role in mediating both opioid and non-opioid type stress-induced analgesia. |
Databáze: | OpenAIRE |
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