Synergistic antinociception between zaprinast and morphine in the spinal cord of rats on the formalin test

Abstract

Intrathecal zaprinast and morphine are effective against acute pain and facilitated pain state. Zaprinast interacts synergistically with morphine.

Additive Antinociception between Intrathecal Sildenafil and Morphine in the Rat Formalin Test

“…Intrathecal morphine reduced the flinching response in both phases of the formalin test in the present study, corroborating with previous results (11-14). Therefore, opioid receptors are involved in the modulation of acute pain as well as the facilitated state.…”

“…These findings suggest that sildenafil may be active against acute pain and the facilitated state at the spinal level, which is consistent with the previous observation (9). Another cGMP-specific phosphodiesterase inhibitor, zaprinast, was effective to attenuate the nociception induced by formalin (14). Therefore, it is conceivable that the increased cGMP level by inhibition of phosphodiesterase may contribute to the antinociception in the spinal cord.…”

“…Thus, sildenafil may not interact with morphine in a synergistic fashion. On the other hand, zaprinast, another phosphodiesterase inhibitor, interacted synergistically with morphine in the spinal cord (14). Moreover, local sildenafil increased the antinociception produced by morphine (25).…”

“…Recently, it has been reported that intrathecal sildenafil produced an antinociception, which is mediated through the nitric oxide (NO)-cGMP pathway (9, 10). It is demonstrated that morphine reversed not only acute nociception but also tissue injury hyperalgesia through the action on spinal opioid receptor (11-14). Furthermore, several lines of evidence suggest that opioid-induced antinociception may be related to the activation of the NO-cGMP pathway (15-17).…”

Endogenous opiates and behavior: 2009

“…The I2-imidazoline binding site ligand, phenyzoline enhanced morphine analgesia on the tail-flick and hot-plate tests, whereas its ortho-phenyl derivative decreased this response (394). Synergistic analgesia occurs between the phosphodiesterase inhibitor, zaprinast and morphine in the spinal cord of rats on the formalin test (1276), whereas riboflavin enhanced this measure as well (84). Blockers of the gap junction channel, carbenoxolone and Gap27 reduced morphine analgesia after intrathecal administration (1090).…”