ATP-sensitive K+ channels are involved in the mediation of intrathecal norepinephrine- or morphine-induced antinociception at the spinal level: a study using EMG planimetry of flexor reflex in rats.
The effects of intrathecally (IT) administered glibenclamide (Gli), an ATP-sensitive K+ (KATP) channel blocker, on the antinociception produced by IT norepinephrine (NE), serotonin (5-HT), morphine (Mor), or adenosine agonist, 5'-N-ethylcarboxamide adenosine (NECA) were investigated using integrated EMG measurement of hindlimb flexor reflex (FR) in lightly pentobarbital-anesthetized rats. The results showed that: 1) NE (3, 6, or 12 nmol) or 5-HT (60, 120, or 240 nmol) each produced a dose-dependent suppression of FR EMG, respectively; 2) pretreatment with Gli (5, 10, or 20 nmol) antagonized the NE (6 nmol)-induced antinociception in a dose-dependent manner and failed to modulate the 5-HT (120 nmol)-induced suppression of FR EMG; 3) pretreatment with Gli (5, 10, or 20 nmol) also antagonize the Mor (2 nmol)-induced suppression of FR EMG in a dose-dependent manner; 4) pretreatment with naloxone (Nal, 60, 120, or 240 nmol) also antagonize the NE (6 nmol)-induced suppression of FR EMG in a dose-dependent manner; and 5) NECA (0.5, 1.0, or 2.0 nmol) produced a dose-dependent suppression of FR EMG, while pretreatment with Gli (5, 10, or 20 nmol) failed to modulate the NECA (1.0 nmol)-induced suppression of FR EMG. The results show that (a) ATP-sensitive K+ channels are involved in the NE- and Mor-induced antinociception but not 5-HT- or NECA-induced antinociception at the spinal level; (b) endogenous opioids might act as a successor of NE and then activate KATP channels to producing the antinociception.
Kang
Y M
YM
Department of Neurobiology, Shanxi Medical College, Taiyuan.
Zhang
Z H
ZH
Yang
S W
SW
Qiao
J T
JT
Dafny
N
N
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D005905:Glyburide / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012026:Reflex, Stretch / Q000187:drug effects*
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D015221:Potassium Channels; D009270:Naloxone; D009020:Morphine; D000255:Adenosine Triphosphate; D005905:Glyburide; D009638:Norepinephrine