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 44degrees 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 microg 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 microg (P < 0.001) of SHG. 1 microg of noradrenaline, but not 0.5 microg, 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.

Concentration-effect relationship of intrapritoneal administration of 1, 25 [OH] 2-vitamin D in a chronic constriction model of neuropathic pain

Introduction: The presence of nuclear receptors of 1, 25 dihydroxy vitamin D3 [1, 25 vit D3], the biologically active metabolite of vitamin D, in neurons and glial cells indicates the biological effect of this vitamin in the nervous system. The present experiment was conducted to identify the effects of different doses of 1, 25 vit D3 on mechanical and cold allodynia in rodent model of neuropatinc pain. Methods: A mononeuropathy was produced by chronic constrictive injury [CCI] of the sciatic nerve. 1, 25 vit D3 [0.3, 0.6, 1 micro g/Kg] was administered by an i.p. injection every 2 days during a month after CCI. Mechanical and cold allodynia were evaluated by Von frey filament and acetone respectively. Results: These findings revealed the exaggerated responses in the group which received CCI. The group which was treated by 1 micro g/kg of 1, 25 vit D3 showed a significant reduction in pain behavior. Injection of 1, 25 vit D3 did not change the response of animals to the acetone drop and von frey filament. Discussion: Our results showed that antinoceptive effect of 1, 25 vit D3 in a rodent neuropathic pain model is dose dependent and this vitamin may provide new approach for treatment of chronic pain

Effect of intrathecal transplantation of adrenal medullary tissue on the sciatic nerve regeneration following chronic constriction injury in the rat

It has been demonstrated that the adrenal medullary transplants into the spinal subarachnoid space can alleviate neuropathic pain behaviors. The aim of the present study was to test the possibility that histological changes of the sciatic nerve in a neuropathic model as well as sensory dysfunction are repaired by adrenal medullary transplantation. Left sciatic nerve was ligated in three groups of rats by 4 loose ligatures [CCI]. After one week of nerve constriction, rats of first group were implanted with adrenal medullary tissue [CCI + adrenal medulla] and rats of the second group with striated muscle at the level of L1-L2 [CCI + muscle]. The third group received only left ligature [CCI] and in the fourth group the sciatic nerve was exposed and then muscle and skin sutured [sham]. Behavioral assessment was evaluated before surgery and 2, 4, 7, 10, 14, 21, 28, 42, and 56 days after the onset of experiment. According to behavioral results, 4 rats in each group were anesthetized and then the distal part of sciatic nerve were isolated and prepared for histological quantitative investigation of nerve regeneration. The results showed that CCI was accompanied with hyperalgesia and morphological changes in the distal part of sciatic nerve. In animals with adrenal medullary transplantation, not only hyperalgesia was markedly reduced or even eliminated, but also the number of myelinated fibers in the distal segment of nerve increased to nearly normal. Our findings showed that the implantation of adrenal medullary tissue might have caused regeneration of ligated nerves as well as alleviation of pain behavior