| Orphanin FQ/Nociceptin involved in the Neuropathic Painand Electro-Acupuncture Analgesia in RatsOrphanin FQ/ nociceptin (OFQ), a member of opioids family found in 1995, is an endogenous ligand of opioid receptor like receptor (ORL1), which has been identified as a member of opioids receptor family. OFQ is a 17 amino-acid peptide (FGGFTGARKSARKLANQ). In spite of its structural homology with the endogenous opioid peptides (especially dynorphin A), OFQ has high affinity to ORL1 receptor but does not show appreciable binding to either μ, δ or κ receptors. OFQ and ORL1 receptor are distributed widely in central nervous system, and have been shown to play a role in lots of physiological functions, such as pain modulation, motor modulation, suppression spatial learning and stimulation of food intake. In pain modulation, the role of supraspinal OFQ and spinal OFQ is different. Substantial evidences have indicated that spinal OFQ produced analgesia and potentiated morphine analgesia but supraspinal OFQ induced hyperalgesia and antagonized morphine analgesia. In the inflammatory pain rat model, the previous study in our lab showed that i.t. OFQ inhibited formalin-induced hyperalgesia. Neuropathic pain is a commonly chronic pain in clinics, and there are some nervous plasticity changes in neuropathic pain. It is unclear that what's the role of OFQ playing during neuropathic pain. In the chronic pathological pain rat model, chronic constriction injury (CCI) to rat sciatic nerve induced neuropathic pain was used as an animal model in our experiment. Four 4-0 gut sutures were each tied loosely with a square knot around the left sciatic nerve. The hyperalgesia appeared 3 days after the operation, stabled on the 7th day and last over 4 weeks. The result in our previous study has implicated that i.t. OFQ had analgesic effect on CCI induced neuropathic pain in rats. However, further studies are needed to investigate the role of OFQ in neuropathic pain. Numerous reports have indicated that electro-acupuncture (EA) has analgesic effect and has been used in clinics as a method of pain treatment, and EA has super effect on chronic pain especially on neuropathic pain. Studies show that EA plays its analgesic role via activating the endogenous pain modulating systems, i.e., opioid system. The role of OFQ playing in EA analgesia in neuropathic pain is still unclear. In the study we are to investigate the role of OFQ in the neuropathic pain rats and EA analgesia, and explore the mechanism further. In the present studies, we observed the analgesic effect of spinal OFQ in the neuropathic pain rats and EA analgesia, and investigated the changes of OFQ and its receptor in spinal and brain levels in neuropathic pain and EA analgesia.It was reported that the plasticity changes in CNS took place in the neuropathic pain and the high activity of glutamate system was an important reason for hyperalgesia of the neuropathic pain rats. Some studies have shown that protein kinase A (PKA) was involved in neuropathic pain. It was also unclear whether cAMP-PKA is one of intracellular signal pathway in OFQ analgesia. Then, another part of our studies was to explore the relationship of OFQ and glutamate system, and the signal transduction pathway of OFQ.By using the molecular biological techniques, including in situ hybridization, immuneohistochemistry, double labeled of fluorescein and Western-Blot in CCI-induced neuropathic pain rats, the present study was designed to observe the role of OFQ in neuropathic pain and EA analgesia, investigate the changes of OFQ system in neuropathic pain and EA analgesia, and explore the mechanism and the intracellular signal pathway of OFQ. The results are following:The role of spinal OFQ in neuropathic pain and EA analgesia1.1 Effects of i.t. OFQ on hyperalgesia of the neuropathic pain ratsOn day 7 after CCI, 3, 10, 30 μg OFQ and NS were i.t. administered in the neuropathic pain rats. 0, 10, 20, 30, 60, 90 min after OFQ administration,changes of paw withdrawal laten...
|
PDF Full Text Request