The critical role of spinal 5-HT7 receptors in opioid and non-opioid type stress-induced analgesia.
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.
Dept of Pharmacology, Gulhane Academy of Medicine, Ankara, Turkey. Electronic address: oyesilyurt@gata.edu.tr.
Ozgur
O
Yesilyurt
Dept of Pharmacology, Gulhane Academy of Medicine, Ankara, Turkey.
Melik
M
Seyrek
Dept of Neurology, Gulhane Academy of Medicine, Ankara, Turkey.
Serdar
S
Tasdemir
Dept of Neurosurgery, Gulhane Academy of Medicine, Ankara, Turkey; Dept of Neurosurgery Yeniyuzyil University, Istanbul, Turkey.
Serdar
S
Kahraman
Dept of Pathology, Gulhane Academy of Medicine, Ankara, Turkey.
Mehmet Salih
MS
Deveci
Dept of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
Emre
E
Karakus
Dept of Pharmacology, Gulhane Academy of Medicine, Ankara, Turkey; Dept of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
Zekai
Z
Halici
Dept of Pharmacology, Gulhane Academy of Medicine, Ankara, Turkey; Pain Research Center, Gulhane Academy of Medicine, Ankara, Turkey.
Ahmet
A
Dogrul
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D058748:Pain Perception / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology
D010636:Phenols; D012333:RNA, Messenger; D011957:Receptors, Opioid; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor
5-HT(7) receptors; Serotonin; Stress-induced analgesia