title: Minocycline prevents dynorphin-induced neurotoxicity during neuropathic pain in rats.
abstract: Despite many advances, our understanding of the involvement of prodynorphin systems in the development of neuropathic pain is not fully understood. Recent studies suggest an important role of neuro-glial interactions in the dynorphin effects associated with neuropathic pain conditions. Our studies show that minocycline reduced prodynorphin mRNA levels that were previously elevated in the spinal and/or dorsal root ganglia (DRG) following sciatic nerve injury. The repeated intrathecal administration of minocycline enhanced the analgesic effects of low-dose dynorphin (0.15 nmol) and U50,488H (25-100 nmol) and prevented the development of flaccid paralysis following high-dose dynorphin administration (15 nmol), suggesting a neuroprotective effect. Minocycline reverts the expression of IL-1β and IL-6 mRNA within the spinal cord and IL-1β mRNA in DRG, which was elevated following intrathecal administration of dynorphin (15 nmol). These results suggest an important role of these proinflammatory cytokines in the development of the neurotoxic effects of dynorphin. Similar to minocycline, a selective inhibitor of MMP-9 (MMP-9 levels are reduced by minocycline) exerts an analgesic effect in behavioral studies, and its administration prevents the occurrence of flaccid paralysis caused by high-dose dynorphin administration (15 nmol). In conclusion, our results underline the importance of neuro-glial interactions as evidenced by the involvement of IL-1β and IL-6 and the minocycline effect in dynorphin-induced toxicity, which suggests that drugs that alter the prodynorphin system could be used to better control neuropathic pain.
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Rojewska
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
authors.forename: Wioletta
authors.initials: W
authors.lastname: Makuch
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Przewlocka
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland. Electronic address: joamika@if-pan.krakow.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Mika
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004399:Dynorphins / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology; D007278:Injections, Spinal; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology*; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010264:Paraplegia / Q000503:physiopathology / Q000517:prevention & control; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D020426:Sciatic Neuropathy; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology
chemical_list: D018712:Analgesics, Non-Narcotic; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D008911:Minocycline
keywords: Dynorphin; Interleukins; MMP-9; Microglia; Minocycline; Neuropathic pain