Spinal Antinociceptive Action of Na+-K+Pump Inhibitor Ouabain and Its Interaction with Morphine and Lidocaine in Rats 

Abstract

Intrathecally administered ouabain produces antinociception, at least in part, via an enhancement of cholinergic transmission in the spinal nociceptive processing system. The results of the interaction of ouabain with morphine and lidocaine suggest that modulation of Na+-,K+-electrochemical gradients and thus subsequent release of neurotransmitters in the spinal cord are likely to play important roles in the spinal antinociceptive effect of intrathecally administered ouabain.

Role of Na+,K+-ATPase in Morphine-Induced Antinociception

“…These results demonstrate a difference between the effects of i.c.v.-and i.t.-administered ouabain on the morphine-induced antinociception. Previous studies have reported that i.t.-administered ouabain enhanced (Zeng et al, 1999) or did not modify the antinociception induced by i.t. morphine (Horvath et al, 2003).…”

“…It has been shown that i.t. administration of ouabain enhanced (Zeng et al, 1999) or did not modify the antinociception induced by i.t. morphine (Horvath et al, 2003) and produced a small antagonism of the effect of low (but not high) doses of i.t.…”

Antinociceptive Synergistic Interaction Between Clonidine and Ouabain on Thermal Nociceptive Tests in the Rat

“…All surgical procedures were performed with the rats under intraperitoneal midazolam (2 mg/kg) and ketamine (40 mg/kg) anesthesia. Using the method described by Zeng et al, 29 an intrathecal catheter (PE-10, 8.5 cm) was inserted through an opening in the cisternal magna to the lumbar subarachnoid space. After surgery, animals were allowed to recover for 1 week before the administration of drugs.…”

“…We have also reported that intrathecally administered ouabain potentiated the antinociceptive synergistic interaction with morphine. 29 However, the interactions of the inhibitor of Na ϩ , K ϩ -ATPase, and ␣ 2 -adrenergic agonist on antinociception at the spinal cord level have not been reported. In the present study, on conscious rats, we examined whether intrathecal ouabain modulates the antinociceptive action of spinal clonidine on somatic nociception.…”

Intrathecal Catheter Insertion and Analgesia is a Safe and Effective Method of Pain Control in Patients with Advanced and Intractable Cancer Pain

“…In addition, combination therapy reduced the development of opioid tolerance while proving synergistic analgesic effects [19]. While the mechanisms of synergism are not completely known, this has been postulated to be in part due to the modulation of Na+-, K+-electrochemical gradients and thus subsequent release of neurotransmitters in the spinal cord resulting in an enhancement of cholinergic transmission in the spinal nociceptive processing system [20].…”