Pre‐emptive analgesia and its supraspinal mechanisms: enhanced descending inhibition and decreased descending facilitation by dexmedetomidine

• Published in: The Journal of physiology 2016-04, Vol.594 (7), p.1875-1890
• Main Authors: You, Hao‐Jun, Lei, Jing, Xiao, Ying, Ye, Gang, Sun, Zhi‐Hong, Yang, Lan, Niu, Nan
• Format: Article
• Language: English
• Subjects: Analgesics, Non-Narcotic - administration & dosage; Analgesics, Non-Narcotic - pharmacology; Analgesics, Non-Narcotic - therapeutic use; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacology; Analgesics, Opioid - therapeutic use; Animals; Cognitive and Behavioural Neuroscience; Dexmedetomidine - administration & dosage; Dexmedetomidine - pharmacology; Dexmedetomidine - therapeutic use; Fentanyl - administration & dosage; Fentanyl - pharmacology; Fentanyl - therapeutic use; Hyperalgesia - drug therapy; Imidazoles - pharmacology; Male; Neural Circuits and Systems; Neural Inhibition; Neuroscience ‐ Behavioural/Systems/Cognitive; Nociception; Pain Threshold; Piperazines - pharmacology; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Research Paper; Thalamic Nuclei - drug effects; Thalamic Nuclei - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/JP271991

Key points Despite the clinical importance of pre‐emptive analgesia, the mechanisms by which it attenuates pain associated with central sensitization are poorly understood. We find that fentanyl and the α2‐adrenoceptor agonist dexmedetomidine (Dex) differ significantly in their modulatory actions on noxious mechanical and noxious heat‐evoked nociception in vivo. Unlike fentanyl, Dex modified descending control of nociception by decreasing the threshold for descending inhibition and/or increasing the threshold for descending facilitation. Dex exhibited after‐actions on activities of thalamus in prolongation of noxious heat‐evoked paw withdrawal latency that persisted for at least 7 days. This study provides insight into the organization of thalamic modulation in pre‐emptive analgesia. We investigated and compared the antinociceptive effects of intraperitoneal administration of fentanyl (2–60 μg kg−1) and dexmedetomidine (Dex, 1–10 μg kg−1; a highly selective α2‐adrenoceptor agonist) in the regulation of nociception assessed by measuring noxious paw withdrawal reflexes in rats. Fentanyl elevated noxious mechanical paw withdrawal threshold and prolonged paw withdrawal heat latency within 1–1.5 h (P