Anti-allodynic Efficacy of NMDA Antagonist Peptide and Noradrenaline Alone and in Combination in Rodent Neuropathic Pain Model

Background: The present experiment was conducted to identify the cooperative effect of serine histogranin (SHG) and noradrenaline in alleviating peripheral neuropathic pain. Methods: Chronic constriction injury of the right sciatic nerve was used to induce chronic neuropathic pain. For drug delivery, a PE10 tube was inserted into the subarachnoid space. Acetone drops and a $44^{\circ}C$ water bath were used to evaluate the cold and heat allodynia, respectively. Placing and grasping reflexes were used to assess the locomotor system. Results: SHG at 0.5 and $1{\mu}g$significantly (P < 0.05) decreased the thermal allodynia. The cold allodynia was also significantly reduced by intrathecal injections of 0.5 (P < 0.05) and $1{\mu}g$(P < 0.001) of SHG. $1{\mu}g$of noradrenaline, but not $0.5{\mu}g$, significantly alleviated the cold (P < 0.01) and thermal (P < 0.05) allodynia. The ameliorating effect of noradrenaline or SHG disappeared when the two compounds were administrated in equal concentrations. A significant difference (P < 0.01 in the acetone and P < 0.05 in the heat) was observed in the groups under equal doses of the two compounds, with a lower effectiveness of the combination therapy. Conclusions: Our findings suggest that the simultaneous administrations of noradrenaline and SHG do not result in synergistic analgesia, and combination therapy may not be a good approach to the treatment of chronic neuropathic pain syndrome.