Starowicz Katarzyna, Przewlocki Ryszard, Gispen Willem Hendrik, Przewlocka Barbara
Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Str., 31-343 Cracow, Poland.
Neuroreport. 2002 Dec 20;13(18):2447-52. doi: 10.1097/00001756-200212200-00015.
Co-localization of opioid and melanocortin receptor expression, especially at the spinal cord level in the dorsal horn and in the gray matter surrounding the central canal led to the suggestion that melanocortins might play a role in nociceptive processes. In the present studies, we aimed to determine the effects of melanocortins, administered intrathecally, on allodynia, and to ascertain whether there is an interaction between opioid and melanocortin systems at the spinal cord level. Neuropathic pain was induced by chronic constriction injury (CCI) of the right sciatic nerve in rats. Tactile allodynia was assessed using von Frey filaments, while thermal hyperlagesia was evaluated in cold water allodynia test. In the present experiments, melanocortin receptor antagonist, SHU9119 was much more potent than mu-opioid receptor agonist, morphine after their intrathecal (i.th.) administration in neuropathic rats. SHU9119 alleviated allodynia in a comparable manner to DAMGO, a selective and potent mu-opioid receptor agonist. Administration of melanocortin receptor agonist, melanotan-II (MTII) increased the sensitivity to tactile and cold stimulation. Moreover, we demonstrated that the selective blockade of mu-opioid receptor by cyprodime (CP) enhanced antiallodynic effect of SHU9119 as well as pronociceptive action of MTII, whereas the combined administration of mu receptor agonist (DAMGO) and SHU9119 significantly reduced the analgesic effect of those ligands. DAMGO also reversed the proallodynic effect of melanocortin receptor agonist, MTII. In conclusion, it seems that the endogenous opioidergic system acts as a functional antagonist of melanocortinergic system, and mu-opioid receptor activity appears to be involved in the modulation of melanocortin system function.
阿片类和黑皮质素受体表达的共定位，尤其是在脊髓背角和围绕中央管的灰质水平，提示黑皮质素可能在伤害感受过程中发挥作用。在本研究中，我们旨在确定鞘内注射黑皮质素对异常性疼痛的影响，并确定阿片类和黑皮质素系统在脊髓水平是否存在相互作用。通过对大鼠右侧坐骨神经进行慢性缩窄损伤（CCI）诱导神经性疼痛。使用von Frey细丝评估触觉异常性疼痛，同时在冷水异常性疼痛试验中评估热痛觉过敏。在本实验中，鞘内注射后，黑皮质素受体拮抗剂SHU9119比μ-阿片受体激动剂吗啡在神经性大鼠中更有效。SHU9119减轻异常性疼痛的方式与选择性强效μ-阿片受体激动剂DAMGO相当。黑皮质素受体激动剂黑素otan-II（MTII）的给药增加了对触觉和冷刺激的敏感性。此外，我们证明环丙吗啉（CP）对μ-阿片受体的选择性阻断增强了SHU9119的抗异常性疼痛作用以及MTII的促伤害感受作用，而μ受体激动剂（DAMGO）和SHU9119的联合给药显著降低了这些配体的镇痛作用。DAMGO还逆转了黑皮质素受体激动剂MTII的促异常性疼痛作用。总之，内源性阿片能系统似乎作为黑皮质素能系统的功能性拮抗剂起作用，并且μ-阿片受体活性似乎参与黑皮质素系统功能的调节。
