Increased prostaglandin E2 release and activated Akt/beta-catenin signaling pathway occur after opioid withdrawal in rat spinal cord.

Background: Prostaglandin E(2) is an important spinal modulator of nociception. However, the effects of chronic opioid administration and withdrawal on prostaglandin E(2) release and associated signaling pathways in the spinal cord are generally unknown.

Methods: This study sought to examine these effects using a spinal microdialysis technique in a model of chronic morphine administration and withdrawal in the rat.

Effects of recurrent withdrawal on spinal GABA release during chronic morphine infusion in the rat.

Chronic opioid administration is associated with altered nociception. The mechanisms underlying these changes are not fully understood. Nociceptive transmission within the spinal cord is modulated by both excitatory and inhibitory neurotransmitters.

Ketorolac prevents recurrent withdrawal induced hyperalgesia but does not inhibit tolerance to spinal morphine in the rat.

Chronic use of opioid is associated with pro-nociceptive phenomena such as hyperalgesia or tolerance. The interaction between opioid and non-steroidal anti-inflammatory drugs (NSAIDs) with respect to opioid-associated hyperalgesia and tolerance remains largely unknown. This study examines the effect of subcutaneous or intrathecal administration of ketorolac, an NSAID, on recurrent withdrawal induced hyperalgesia and tolerance to spinal morphine in rats.

Periodic abstinence enhances nociception without significantly altering the antinociceptive efficacy of spinal morphine in the rat.

Naloxone administration in the opioid dependent rat is associated with spinal glutamate release and NMDA receptor activation which reportedly is also responsible for opioid tolerance. We hypothesized that episodic withdrawal during chronic infusion of spinal morphine might paradoxically enhance tolerance. Rats (24/group) infused with intrathecal morphine (M) for 4 days (20 nmol/microl per h) were given a daily subcutaneous (s.