Participation of ATP-sensitive K+ channels in the peripheral antinociceptive effect of fentanyl in rats

• Published in: Brazilian journal of medical and biological research Vol. 38; no. 1; pp. 91 - 97
• Main Authors: Rodrigues, A R A, Castro, M S A, Francischi, J N, Perez, A C, Duarte, I D G
• Format: Journal Article
• Language: English
• Published: Brazil Associação Brasileira de Divulgação Científica 01.01.2005
• Subjects: Analgesia; Analgesics, Opioid - antagonists & inhibitors; Analgesics, Opioid - pharmacology; Animals; BIOLOGY; Carrageenan; Dose-Response Relationship, Drug; Fentanyl; Fentanyl - antagonists & inhibitors; Fentanyl - pharmacology; Glibenclamide; K+ channel; Male; MEDICINE, RESEARCH & EXPERIMENTAL; Pain - chemically induced; Pain - drug therapy; Pain Measurement - drug effects; Peripheral antinociception; Potassium Channel Blockers - pharmacology; Potassium Channels - drug effects; Potassium Channels, Calcium-Activated; Rats; Rats, Wistar; Receptors, Opioid, mu; µ-Opioid receptor agonist; K+ channel; Fentanyl; µ-Opioid receptor agonist; Glibenclamide; Peripheral antinociception
• ISSN: 0100-879X; 1414-431X; 0100-879X; 1414-431X
• DOI: 10.1590/S0100-879X2005000100014

We examined the effect of several K+ channel blockers such as glibenclamide, tolbutamide, charybdotoxin (ChTX), apamin, tetraethylammonium chloride (TEA), 4-aminopyridine (4-AP), and cesium on the ability of fentanyl, a clinically used selective micro-opioid receptor agonist, to promote peripheral antinociception. Antinociception was measured by the paw pressure test in male Wistar rats weighing 180-250 g (N = 5 animals per group). Carrageenan (250 microg/paw) decreased the threshold of responsiveness to noxious pressure (delta = 188.1 +/- 5.3 g). This mechanical hyperalgesia was reduced by fentanyl (0.5, 1.5 and 3 microg/paw) in a peripherally mediated and dose-dependent fashion (17.3, 45.3 and 62.6%, respectively). The selective blockers of ATP-sensitive K+ channels glibenclamide (40, 80 and 160 microg/paw) and tolbutamide (80, 160 and 240 microg/paw) dose dependently antagonized the antinociception induced by fentanyl (1.5 microg/paw). In contrast, the effect of fentanyl was unaffected by the large conductance Ca2+-activated K+ channel blocker ChTX (2 microg/paw), the small conductance Ca2+-activated K+ channel blocker apamin (10 microg/paw), or the non-specific K+ channel blocker TEA (150 microg/paw), 4-AP (50 microg/paw), and cesium (250 microg/paw). These results extend previously reported data on the peripheral analgesic effect of morphine and fentanyl, suggesting for the first time that the peripheral micro-opioid receptor-mediated antinociceptive effect of fentanyl depends on activation of ATP-sensitive, but not other, K+ channels.