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Activation of NK-1 receptor in the locus coeruleus exerts analgesic effect on neuropathic pain though noradrenergic descending inhibition
| Content Provider | Semantic Scholar |
|---|---|
| Author | Muto, Y. Sakamoto, Atsuhiro Suzuki, Hidenori |
| Copyright Year | 2011 |
| Abstract | Neuropathic pain is intractable chronic pain resistant to conventional analgesics. Although noradrenergic drugs are effective in alleviating the pain in some cases, severe adverse effects limit its usefulness. Therefore, the activation of endogenous noradrenergic system involved in nociception may have potential as analgesic strategy with less adverse effects. The locus coeruleus (LC) is one of the noradrenergic neuronal nuclei involved in descending modulation of pain. It is reported that NK-1 receptor is expressed in the LC. In this study, we therefore examined whether substance P (SP), an endogenous ligand for NK-1 receptor, contributes to alleviating neuropathic pain. As a neuropathic pain model, chronic constrictive injury was performed on the left sciatic nerve of rats. SP was microinjected into the left LC through implanted cannula at day 7 after CCI, at which time point the neuropathic pain was established. Five minutes after SP injection, both mechanical allodynia and thermal hyperalgesia were significantly inhibited. These analgesic effects were completely blocked with the prior injection of an NK-1 receptor antagonist, WIN 51704, into the LC. In addition, the intrathecal administration of an 2-adrenoceptor antagonist, yohimbine, also blocked the analgesic effects of SP injected into the LC. Since the present study suggests that SP facilitates the descending inhibition by noradrenergic LC neurons to relieve neuropathic pain, the strategy to efficiently activate this pathway may provide a potential medication for neuropathic pain. |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.neures.2011.07.1577 |
| Volume Number | 71 |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S0168010211017603 |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S0168010211017603?dgcid=api_sd_search-api-endpoint |
| Alternate Webpage(s) | https://doi.org/10.1016/j.neures.2011.07.1577 |
| Journal | Neuroscience Research |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
