Polyamine deprivation alters formalin-induced hyperalgesia and decreases morphine efficacy

Although the exact functions of polyamines in the nervous system remain sti ll unclear, they are thought to have a physiological role in intracellular signal processing and neurotransmission. Polyamine deprivation which consis ts in the reduction of both the endogenous and exogenous sources of polyami nes is a promising treatment for cancer. In a previous study we have shown that this treatment provokes an analgesic effect in rats submitted to brief phasic nociceptive tests. The present study examined the effect of polyami ne deprivation on pain-related behaviors and spinal c-fos expression evoked in the formalin test presumed to better reflect clinical pain, using morph ine as analgesia control. Polyamine deprivation per se altered the characte ristic pain-related behaviors, reducing the interphase depression of pain, without inducing changes in the spinal Fos staining. In addition this treat ment prevented the antinociceptive effect of morphine both on behavioral re sponses and on spinal c-fos expression. In polyamine-deprived rats, despite morphine injection, nociceptive scores remained dramatically high during t he intermediate and the late phases of the response and the number of Fos i mmunoreactive neurons remained largely higher in deeper layers than in morp hine control rats. Altogether these data support a modulatory role of polya mines both on the neuronal circuitry mediating sensory information, and on mechanisms underlying morphine analgesia.