title: Minocycline enhances the effectiveness of nociceptin/orphanin FQ during neuropathic pain.
abstract: Nociceptin/orphanin FQ (N/OFQ) antinociception, which is mediated selectively by the N/OFQ peptide receptor (NOP), was demonstrated in pain models. In this study, we determine the role of activated microglia on the analgesic effects of N/OFQ in a rat model of neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve. Repeated 7-day administration of minocycline (30 mg/kg i.p.), a drug that affects microglial activation, significantly reduced pain in CCI-exposed rats and it potentiates the analgesic effects of administered N/OFQ (2.5-5 μg i.t.). Minocycline also downregulates the nerve injury-induced upregulation of NOP protein in the dorsal lumbar spinal cord. Our in vitro study showed that minocycline reduced NOP mRNA, but not protein, level in rat primary microglial cell cultures. In [(35)S]GTPγS binding assays we have shown that minocycline increases the spinal N/OFQ-stimulated NOP signaling. We suggest that the modulation of the N/OFQ system by minocycline is due to the potentiation of its neuronal antinociceptive activity and weakening of the microglial cell activation. This effect is beneficial for pain relief, and these results suggest new targets for the development of drugs that are effective against neuropathic pain.
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Cracow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Popiolek-Barczyk
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Cracow, 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 Cracow, Poland.
authors.forename: Agnieszka M
authors.initials: AM
authors.lastname: Jurga
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Cracow, Poland.
authors.forename: Wioletta
authors.initials: W
authors.lastname: Makuch
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt 62 Street, Szeged 6726, Hungary.
authors.forename: Ferenz
authors.initials: F
authors.lastname: Zador
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt 62 Street, Szeged 6726, Hungary.
authors.forename: Anna
authors.identifier: 0000-0001-6187-1406
authors.initials: A
authors.lastname: Borsodi
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Cracow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Piotrowska
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Cracow, 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 Cracow, Poland.
authors.forename: Joanna
authors.identifier: 0000-0003-1986-7205
authors.initials: J
authors.lastname: Mika
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008954:Models, Biological; D009437:Neuralgia / Q000188:drug therapy* / Q000473:pathology; D018847:Opioid Peptides / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D008911:Minocycline; D018847:Opioid Peptides; D012333:RNA, Messenger; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat