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With the aim of assessing its therapeutic potential, we examined the effect of antisense oligonucleotide knockdown of spinal metabotropic glutamate receptor 1 (mGluR<jats:sub>1<\/jats:sub>) in neuropathic rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We chronically infused rats intrathecally with either vehicle, or 50\u2003\u03bcg day<jats:sup>\u22121<\/jats:sup> antisense or missense oligonucleotides beginning either 3 days prior to or 5 days after nerve injury. Cold, heat and mechanical sensitivity was assessed prior to any treatment and again every few days after nerve injury.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Here we show that knockdown of mGluR<jats:sub>1<\/jats:sub> significantly reduces cold hyperalgesia, heat hyperalgesia and mechanical allodynia in the ipsilateral (injured) hindpaw of neuropathic rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Moreover, we show that morphine analgesia is reduced in neuropathic rats, but not in sham\u2010operated rats, and that knockdown of mGluR<jats:sub>1<\/jats:sub> restores the analgesic efficacy of morphine.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We also show that neuropathic rats are more sensitive to the excitatory effects of intrathecally injected N\u2010methyl\u2010D\u2010aspartate (NMDA), and have elevated protein kinase C (PKC) activity in the spinal cord dorsal horn, two effects that are reversed by knockdown of mGluR<jats:sub>1<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results suggest that activity at mGluR<jats:sub>1<\/jats:sub> contributes to neuropathic pain through interactions with spinal NMDA receptors and PKC, and that knockdown of mGluR<jats:sub>1<\/jats:sub> may be a useful therapy for neuropathic pain in humans, both to alleviate pain directly, and as an adjunct to opioid analgesic treatment.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>132<\/jats:bold>, 354\u2013367; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703810\">10.1038\/sj.bjp.0703810<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703810","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:06:00Z","timestamp":1106946360000},"page":"354-367","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Knockdown of spinal metabotropic glutamate receptor 1 (mGluR<sub>1<\/sub>) alleviates pain and restores opioid efficacy after nerve injury in rats"],"prefix":"10.1111","volume":"132","author":[{"given":"Marian E","family":"Fundytus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Yashpal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Guy","family":"Chabot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G","family":"Osborne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste D","family":"Lefebvre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Dray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence J","family":"Coderre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"13361","DOI":"10.1016\/S0021-9258(18)42219-3","article-title":"Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate\/Ca2+ signal transduction","volume":"267","author":"ABE T.","year":"1992","journal-title":"J. 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