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 (GH), an ATP-sensitive K⁺ (K(ATP)) 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 K(ATP) channels to producing the antinociception.