The very-high-efficacy 5-HT1A receptor agonist, F 13640, preempts the development of allodynia-like behaviors in rats with spinal cord injury.
Central neuropathic pain after spinal cord injury (SCI) presents a challenging clinical problem with limited treatment options. [(3-chloro-4-fluoro-phenyl)-[4-fluoro-4-([(5-methyl-pyridin-2-ylmethyl)-amino]-methyl)piperidin-1-yl]]-methadone (F 13640) is a recently discovered very-high-efficacy, selective 5-HT1A receptor agonist that produces a remarkably powerful, central analgesia through unprecedented neuroadaptive mechanisms. In a rat model of spinal cord injury pain, we previously found that chronic infusion of F 13640 alleviated pain-like behaviors. Here, we report that infusion of 0.63 mg/day of F 13640 for 8 weeks starting 24 h before the induction of injury significantly attenuates the development of chronic allodynia-like behavior in rats sustaining a photochemically-induced, ischaemic injury of the dorsal laminae of the L3-L5 segments of the spinal cord. Importantly, the preemptive effect of F 13640 persisted for 2 months after treatment was discontinued. The data warrant the study of the possible effects of the early administration of F 13640 in patients sustaining spinal cord injury.
Wu
Wei-Ping
WP
Division of Clinical Neurophysiology, Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Huddinge, Sweden.
Hao
Jing-Xia
JX
Xu
Xiao-Jun
XJ
Wiesenfeld-Hallin
Zsuzsanna
Z
Koek
Wouter
W
Colpaert
Francis C
FC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D003080:Cold Temperature; D005260:Female; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000209:etiology / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010777:Photochemistry; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000523:psychology*; D013997:Time Factors; D014828:Vocalization, Animal / Q000187:drug effects
D010880:Piperidines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A; D017366:Serotonin Receptor Agonists; C473959:befiradol