The interaction of morphine and selective serotonin reuptake inhibitors on mechanical allodynia in rats with a spinal nerve ligation. |
Mi young Kwon, In gu Jun, Tae hee Kim, Jong Yeon Park |
Department of Anesthesiology and Pain Medicine, Seoul Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea. jongyeon_park@amc.seoul.kr |
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Abstract |
BACKGROUND Nerve injury may produce a tactile allodynia.
However, there are few reports regarding the interaction of morphine and selective serotonin reuptake inhibitors (SSRIs) during a neuropathic pain state. Therefore, we investigated the antiallodynic interaction between morphine and SSRIs in a rat model of neuropathic pain. METHODS Rats were prepared with a tight ligation of the left fifth and sixth lumbar spinal nerves and chronic intrathecal catheter implantation. Mechanical allodynia was then measured by application of von Frey filaments.
Morphine, citalopram and paroxetine were administered intrathecally to obtain the dose-response curves. The 50% effective dose of morphine and citalopram or paroxetine were then coadministered to evaluate the drug interaction. In addition, naloxone and methysergide were administered to examine the reversal of the antiallodynic effect. RESULTS Intrathecal morphine produced a dose-dependent antagonism of the tactile allodynia, but intrathecal citalopram or paroxetine showed no antiallodynic effects. In addition, a morphine-citalopram or paroxetine combination produced an increase in the withdrawal threshold, but naloxone and methysergide reversed the antiallodynic effect.
In addition, no interactions were observed between naloxone and citalopram or paroxetine, or morphine and methysergide. CONCLUSIONS These results suggest that activation of both micron-opioid and serotonin receptors is required for the increased interaction to occur between morphine and SSRIs administered to reduce tactile allodynia. Thus, serotonin receptors take part in the antiallodynic action of morphine at the spinal level. |
Key Words:
allodynia; citaloparam; interaction; morphine; paroxetine; serotonin |
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