Top

Inflammopharmacology

Published in:

Open Access 01-04-2018 | Original Article

Evaluation of cebranopadol, a dually acting nociceptin/orphanin FQ and opioid receptor agonist in mouse models of acute, tonic, and chemotherapy-induced neuropathic pain

Authors: Kinga Sałat, Anna Furgała, Robert Sałat

Published in: Inflammopharmacology | Issue 2/2018

Abstract

Background

Cebranopadol (a.k.a. GRT-6005) is a dually acting nociceptin/orphanin FQ and opioid receptor agonist that has been recently developed in Phase 2 clinical trials for painful diabetic neuropathy or cancer pain. It also showed analgesic properties in various rat models of pain and had a better safety profile as compared to equi-analgesic doses of morphine. Since antinociceptive properties of cebranopadol have been studied mainly in rat models, in the present study, we assessed analgesic activity of subcutaneous cebranopadol (10 mg/kg) in various mouse pain models.

Methods

We used models of acute, tonic, and chronic pain induced by thermal and chemical stimuli, with a particular emphasis on pharmacoresistant chronic neuropathic pain evoked by oxaliplatin in which cebranopadol was used alone or in combination with simvastatin.

Key results

As shown in the hot plate test, the analgesic activity of cebranopadol developed more slowly as compared to morphine (90–120 min vs. 60 min). Cebranopadol displayed a significant antinociceptive activity in acute pain models, i.e., the hot plate, writhing, and capsaicin tests. It attenuated nocifensive responses in both phases of the formalin test and reduced cold allodynia in oxaliplatin-induced neuropathic pain model. Its efficacy was similar to that of morphine. Used in combination and administered simultaneously, 4 or 6 h after simvastatin, cebranopadol did not potentiate antiallodynic activity of this cholesterol-lowering drug. Cebranopadol did not induce any motor deficits in the rotarod test.

Conclusion

Cebranopadol may have significant potential for the treatment of various pain types, including inflammatory and chemotherapy-induced neuropathic pain.

Argoff C (2011) Mechanisms of pain transmission and pharmacologic management. Curr Med Res Opin 27(10):2019–2031. doi:10.1185/03007995.2011.614934 CrossRefPubMed

Baumhäkel M, Böhm M (2010) Recent achievements in the management of Raynaud’s phenomenon. Vasc Health Risk Manag 6:207–214CrossRefPubMedPubMedCentral

Bhalla S, Singh N, Jaggi AS (2015) Dose-related neuropathic and anti-neuropathic effects of simvastatin in vincristine-induced neuropathic pain in rats. Food Chem Toxicol 80:32–40. doi:10.1016/j.fct.2015.02.016 CrossRefPubMed

Bird MF, Lambert DG (2015) Simultaneous targeting of multiple opioid receptor types. Curr Opin Support Palliat Care 9:98–102. doi:10.1097/SPC.0000000000000129 CrossRefPubMed

Bombig MT, Ferreira C, Mora O et al (2003) Pravastatin protection from cold stress in myocardium of rats. Jpn Heart J 44(2):243–255CrossRefPubMed

Briscini L, Corradini L, Ongini E, Bertorelli R (2002) Up-regulation of ORL-1 receptors in spinal tissue of allodynic rats after sciatic nerve injury. Eur J Pharmacol 447:59–65. doi:10.1016/S0014-2999(02)01833-2 CrossRefPubMed

Chen Y, Sommer C (2006) Nociceptin and its receptor in rat dorsal root ganglion neurons in neuropathic and inflammatory pain models: implications on pain processing. J Peripher Nerv Syst 11:232–240. doi:10.1111/j.1529-8027.2006.0093.x CrossRefPubMed

Chen XY, Li K, Light AR, Fu KY (2013) Simvastatin attenuates formalin-induced nociceptive behaviors by inhibiting microglial RhoA and p38 MAPK activation. J Pain 14:1310–1319. doi:10.1016/j.jpain.2013.05.011 CrossRefPubMed

Corboz MR, Rivelli MA, Egan RW et al (2000) Nociceptin inhibits capsaicin-induced bronchoconstriction in isolated guinea pig lung. Eur J Pharmacol 402:171–179. doi:10.1016/S0014-2999(00)00505-7 CrossRefPubMed

Corradini L, Briscini L, Ongini E, Bertorelli R (2001) The putative OP4 antagonist, [Nphe1]nociceptin(1-13)NH2, prevents the effects of nociceptin in neuropathic rats. Brain Res 905:127–133. doi:10.1016/S0006-8993(01)02520-3 CrossRefPubMed

Courteix C, Coudoré-Civiale MA, Privat AM et al (2004) Evidence for an exclusive antinociceptive effect of nociceptin/orphanin FQ, an endogenous ligand for the ORL1 receptor, in two animal models of neuropathic pain. Pain 110:236–245. doi:10.1016/j.pain.2004.03.037 CrossRefPubMed

Czopek A, Sałat K, Byrtus H et al (2016) Antinociceptive activity of novel amide derivatives of imidazolidine-2,4-dione in a mouse model of acute pain. Pharmacol Rep 68:529–535. doi:10.1016/j.pharep.2015.12.007 CrossRefPubMed

D’Agostino B, Orlotti D, Calò G et al (2010) Nociceptin modulates bronchoconstriction induced by sensory nerve activation in mouse lung. Am J Respir Cell Mol Biol 42:250–254. doi:10.1165/rcmb.2008-0488OC CrossRefPubMed

Delaney G, Dawe KL, Hogan R et al (2012) Role of nociceptin/orphanin FQ and NOP receptors in the response to acute and repeated restraint stress in rats. J Neuroendocrinol 24:1527–1541. doi:10.1111/j.1365-2826.2012.02361.x CrossRefPubMedPubMedCentral

Eddy NB, Leimbach D (1953) Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. J Pharmacol Exp Ther 107:385–393PubMed

Erb K, Liebel JT, Tegeder I et al (1997) Spinally delivered nociceptin/orphanin FQ reduces flinching behaviour in the rat formalin test. NeuroReport 8:1967–1970CrossRefPubMed

Finnerup NB, Attal N, Haroutounian S et al (2015) Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 14:162–173. doi:10.1016/S1474-4422(14)70251-0 CrossRefPubMedPubMedCentral

Gades NM, Danneman PJ, Wixson SK, Tolley EA (2000) The magnitude and duration of the analgesic effect of morphine, butorphanol, and buprenorphine in rats and mice. Contemp Top Lab Anim Sci 39(2):8–13PubMed

Gavioli EC, Romão PRT (2011) NOP receptor ligands as potential agents for inflammatory and autoimmune diseases. J Amino Acids 2011:836569. doi:10.4061/2011/836569 CrossRefPubMedPubMedCentral

Gavioli EC, de Medeiros IU, Monteiro MC et al (2015) Nociceptin/orphanin FQ-NOP receptor system in inflammatory and immune-mediated diseases. Vitam Horm 97:241–266. doi:10.1016/bs.vh.2014.11.003 CrossRefPubMed

Giuliani S, Lecci A, Maggi CA (2000) Nociceptin and neurotransmitter release in the periphery. Peptides 21:977–984. doi:10.1016/S0196-9781(00)00237-0 CrossRefPubMed

Günther T, Dasgupta P, Mann A et al (2017) Targeting multiple opioid receptors—improved analgesics with reduced side effects? Br J Pharmacol. doi:10.1111/bph.13809 PubMed

Hao S, Ogawa H (1998) Naltrexone, but not atropine or yohimbine, antagonizes suppression of formalin-induced spinal sensitization by intrathecal nociceptin. Life Sci 63:PL 167–73

Hao J-X, Xu IS, Wiesenfeld-Hallin Z, Xu X-J (1998) Anti-hyperalgesic and anti-allodynic effects of intrathecal nociceptin/orphanin FQ in rats after spinal cord injury, peripheral nerve injury and inflammation. Pain 76:385–393. doi:10.1016/S0304-3959(98)00071-2 CrossRefPubMed

Hunskaar S, Hole K (1987) The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 30:103–114. doi:10.1016/0304-3959(87)90088-1 CrossRefPubMed

Inoue M, Shimohira I, Yoshida A et al (1999) Dose-related opposite modulation by nociceptin/orphanin FQ of substance P nociception in the nociceptors and spinal cord. J Pharmacol Exp Ther 291:308–313PubMed

Işeri S, Ercan F, Gedik N, Yüksel M, Alican I (2007) Simvastatin attenuates cisplatin-induced kidney and liver damage in rats. Toxicology 230(2–3):256–264PubMed

Jaiswal SR, Sontakke SD (2012) Experimental evaluation of analgesic and anti-inflammatory activity of simvastatin and atorvastatin. Indian J Pharmacol 44:475–479. doi:10.4103/0253-7613.99311 CrossRefPubMedPubMedCentral

Ju J, Shin DJ, Na YC, Yoon MH (2013) Role of spinal opioid receptor on the antiallodynic effect of intrathecal nociceptin in neuropathic rat. Neurosci Lett 542:118–122. doi:10.1016/j.neulet.2013.03.026 CrossRefPubMed

Kamei J, Ohsawa M, Kashiwazaki T, Nagase H (1999) Antinociceptive effects of the ORL1 receptor agonist nociceptin/orphanin FQ in diabetic mice. Eur J Pharmacol 370:109–116. doi:10.1016/S0014-2999(99)00112-0 CrossRefPubMed

Khroyan TV, Polgar WE, Orduna J et al (2011) Differential effects of NOP receptor agonists in acute versus chronic pain: studies with bifunctional NOP/mu receptor agonists in the sciatic nerve ligation chronic pain model in mice. J Pharmacol Exp Ther 339:687–693. doi:10.1124/jpet.111.184663 CrossRefPubMedPubMedCentral

King MA, Rossi GC, Chang AH et al (1997) Spinal analgesic activity of orphanin FQ/nociceptin and its fragments. Neurosci Lett 223:113–116. doi:10.1016/S0304-3940(97)13414-0 CrossRefPubMed

Knowlton WM, Daniels RL, Palkar R, McCoy DD, McKemy DD (2011) Pharmacological blockade of TRPM8 ion channels alters cold and cold pain responses in mice. PLoS One 6(9):e25894. doi:10.1371/journal.pone.0025894 CrossRefPubMedPubMedCentral

Kono T, Satomi M, Suno M et al (2012) Oxaliplatin induced neurotoxicity involves TRPM8 in the mechanism of acute hypersensitivity to cold sensation. Brain Behav 2(1):68–73. doi:10.1002/brb3.34 CrossRefPubMedPubMedCentral

Lambert DG, Bird MF, Rowbotham DJ (2015) Cebranopadol: a first in-class example of a nociceptin/orphanin FQ receptor and opioid receptor agonist. Br J Anaesth 114:364–366. doi:10.1093/bja/aeu332 CrossRefPubMed

Leggett JD, Harbuz MS, Jessop DS, Fulford AJ (2006) The nociceptin receptor antagonist [Nphe1, Arg14, Lys15]nociceptin/orphanin FQ-NH2 blocks the stimulatory effects of nociceptin/orphanin FQ on the HPA axis in rats. Neuroscience 141:2051–2057. doi:10.1016/j.neuroscience.2006.05.036 CrossRefPubMed

Liang J, Yin K, Cao X et al (2017) Attenuation of low ambient temperature-induced myocardial hypertrophy by atorvastatin via promoting Bcl-2 expression. Cell Physiol Biochem 41(1):286–295. doi:10.1159/000456111 CrossRefPubMed

Linz K, Christoph T, Schiene K, Koch T, Englberger W (2013) GRT-TA2210, a selective NOP receptor agonist, is active in mouse models of inflammatory and neuropathic pain. In: EFIC–8th “Pain in Europe” Congress, 2013 October 9–12, Florence, Italy. Abstract 599

Linz K, Christoph T, Tzschentke TM et al (2014) Cebranopadol: a novel potent analgesic nociceptin/orphanin FQ peptide and opioid receptor agonist. J Pharmacol Exp Ther 349:535–548. doi:10.1124/jpet.114.213694 CrossRefPubMed

Linz K, Schröder W, Frosch S, Christoph T (2017) Opioid-type respiratory depressant side effects of cebranopadol in rats are limited by its nociceptin/orphanin FQ Peptide receptor agonist activity. Anesthesiology 126:708–715. doi:10.1097/ALN.0000000000001530 CrossRefPubMed

Manji H (2013) Drug-induced neuropathies. Handb Clin Neurol 115:729–742. doi:10.1016/B978-0-444-52902-2.00042-4 CrossRefPubMed

Mansouri MT, Khodayar MJ, Tabatabaee A, Ghorbanzadeh B, Naghizadeh B (2015) Modulation of morphine antinociceptive tolerance and physical dependence by co-administration of simvastatin. Pharmacol Biochem Behav 137:38–43. doi:10.1016/j.pbb.2015.08.002 CrossRefPubMed

Mansouri MT, Naghizadeh B, Ghorbanzadeh B, Alboghobeish S (2017) Systemic and local anti-nociceptive effects of simvastatin in the rat formalin assay: role of peroxisome proliferator-activated receptor γ and nitric oxide. J Neurosci Res. doi:10.1002/jnr.24008 PubMed

Marwaha L, Bansal Y, Singh R et al (2016) TRP channels: potential drug target for neuropathic pain. Inflammopharmacology 24:305–317CrossRefPubMed

Massicot F, Hache G, David L et al (2013) P2X7 cell death receptor activation and mitochondrial impairment in oxaliplatin-induced apoptosis and neuronal injury: cellular mechanisms and approach. PLoS One 8:e66830. doi:10.1371/journal.pone.0066830 CrossRefPubMedPubMedCentral

McNamara CR, Mandel-Brehm J, Bautista DM et al (2007) TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci 104:13525–13530. doi:10.1073/pnas.0705924104 CrossRefPubMedPubMedCentral

Micheli L, Di Cesare Mannelli L, Rizzi A et al (2015) Intrathecal administration of nociceptin/orphanin FQ receptor agonists in rats: a strategy to relieve chemotherapy-induced neuropathic hypersensitivity. Eur J Pharmacol 766:155–162. doi:10.1016/j.ejphar.2015.10.005 CrossRefPubMed

Miranda HF, Noriega V, Olavarria L et al (2011) Antinociception and Anti-Inflammation Induced by Simvastatin in Algesiometric Assays in Mice. Basic Clin Pharmacol Toxicol 109:438–442. doi:10.1111/j.1742-7843.2011.00746.x CrossRefPubMed

Nassini R, Gees M, Harrison S et al (2011) Oxaliplatin elicits mechanical and cold allodynia in rodents via TRPA1 receptor stimulation. Pain 152:1621–1631. doi:10.1016/j.pain.2011.02.051 CrossRefPubMed

Nassini R, Fusi C, Materazzi S et al (2015) The TRPA1 channel mediates the analgesic action of dipyrone and pyrazolone derivatives. Br J Pharmacol 172:3397–3411. doi:10.1111/bph.13129 CrossRefPubMedPubMedCentral

Ohsawa M, Ishikura K, Mutoh J, Hisa H (2016) Involvement of inhibition of RhoA/Rho kinase signaling in simvastatin-induced amelioration of neuropathic pain. Neuroscience 333:204–213. doi:10.1016/j.neuroscience.2016.07.029 CrossRefPubMed

Plein LM, Rittner HL (2017) Opioids and the immune system—friend or foe. Br JPharmacol. doi:10.1111/bph.13750

Qiu Y, Chen WY, Wang ZY et al (2016) Simvastatin attenuates neuropathic pain by inhibiting the RhoA/LIMK/Cofilin pathway. Neurochem Res 41(9):2457–2469. doi:10.1007/s11064-0161958-1 CrossRefPubMed

Raffa RB, Burdge G, Gambrah J et al (2017) Cebranopadol: novel dual opioid/NOP receptor agonist analgesic. J Clin Pharm Ther 42:8–17. doi:10.1111/jcpt.12461 CrossRefPubMed

Rizzi A, Nazzaro C, Marzola GG et al (2006) Endogenous nociceptin/orphanin FQ signalling produces opposite spinal antinociceptive and supraspinal pronociceptive effects in the mouse formalin test: pharmacological and genetic evidences. Pain 124:100–108. doi:10.1016/j.pain.2006.03.021 CrossRefPubMed

Sakurada T, Komatsu T, Moriyama T et al (2005) Effects of intraplantar injections of nociceptin and its N-terminal fragments on nociceptive and desensitized responses induced by capsaicin in mice. Peptides 26:2505–2512. doi:10.1016/j.peptides.2005.05.022 CrossRefPubMed

Sałat K, Filipek B (2015) Antinociceptive activity of transient receptor potential channel TRPV1, TRPA1, and TRPM8 antagonists in neurogenic and neuropathic pain models in mice. J Zhejiang Univ B 16:167–178. doi:10.1631/jzus.B1400189 CrossRef

Sałat K, Filipek B, Wiȩckowski K, Malawska B (2009) Analgesic activity of 3-mono-substituted derivatives of dihydrofuran-2-one in experimental rodent models of pain. Pharmacol Rep 61:807–818. doi:10.1016/S1734-1140(09)70136-7 CrossRefPubMed

Sałat K, Librowski T, Moniczewski A et al (2012) Analgesic, antioedematous and antioxidant activity of γ-butyrolactone derivatives in rodents. Behav Pharmacol 23:407–416. doi:10.1097/FBP.0b013e3283566042 CrossRefPubMed

Sałat K, Kulig K, Gajda J et al (2013a) Evaluation of anxiolytic-like, anticonvulsant, antidepressant-like and antinociceptive properties of new 2-substituted 4-hydroxybutanamides with affinity for GABA transporters in mice. Pharmacol Biochem Behav 110:145–153. doi:10.1016/j.pbb.2013.06.013 CrossRefPubMed

Sałat K, Moniczewski A, Librowski T (2013b) Transient receptor potential channels—emerging novel drug targets for the treatment of pain. Curr Med Chem 20:1409–1436. doi:10.2174/09298673113209990107 CrossRefPubMed

Sałat K, Cios A, Wyska E et al (2014) Antiallodynic and antihyperalgesic activity of 3-[4-(3-trifluoromethyl- phenyl)-piperazin-1-yl]-dihydrofuran-2-one compared to pregabalin in chemotherapy-induced neuropathic pain in mice. Pharmacol Biochem Behav 122:173–181. doi:10.1016/j.pbb.2014.03.025 CrossRefPubMed

Sałat K, Jakubowska A, Kulig K (2015a) Cebranopadol: a first-in-class potent analgesic agent with agonistic activity at nociceptin/orphanin FQ and opioid receptors. Expert Opin Investig Drugs 24:837–844. doi:10.1517/13543784.2015.1036985 CrossRefPubMed

Sałat K, Podkowa A, Kowalczyk P et al (2015b) Anticonvulsant active inhibitor of GABA transporter subtype 1, tiagabine, with activity in mouse models of anxiety, pain and depression. Pharmacol Rep 67:465–472. doi:10.1016/j.pharep.2014.11.003 CrossRefPubMed

Schröder W, Lambert DG, Ko MC, Koch T (2014) Functional plasticity of the N/OFQ-NOP receptor system determines analgesic properties of NOP receptor agonists. Br J Pharmacol 171:3777–3800. doi:10.1111/bph.12744 CrossRefPubMedPubMedCentral

Sehgal N, Smith HS, Manchikanti L (2011) Peripherally acting opioids and clinical implications for pain control. Pain Physician 14(3):249–258PubMed

Shah S, Page CP, Spina D (1998) Nociceptin inhibits non-adrenergic non-cholinergic contraction in guinea-pig airway. Br J Pharmacol 125:510–516. doi:10.1038/sj.bjp.0702068 CrossRefPubMedPubMedCentral

Shi XQ, Lim TKY, Lee S et al (2011) Statins alleviate experimental nerve injury-induced neuropathic pain. Pain 152:1033–1043. doi:10.1016/j.pain.2011.01.006 CrossRefPubMed

Singh SR, Sullo N, Matteis M et al (2016) Nociceptin/orphanin FQ (N/OFQ) modulates immunopathology and airway hyperresponsiveness representing a novel target for the treatment of asthma. Br J Pharmacol 173:1286–1301. doi:10.1111/bph.13416 CrossRefPubMedPubMedCentral

Sobczak M, Salaga M, Storr M, Fichna J (2013) Nociceptin/orphanin FQ (NOP) receptors as novel potential target in the treatment of gastrointestinal diseases. Curr Drug Targets 14:1203–1209CrossRefPubMed

Sobczak M, Pilarczyk A, Jonakowski M et al (2014) Anti-inflammatory and antinociceptive action of the dimeric enkephalin peptide biphalin in the mouse model of colitis: new potential treatment of abdominal pain associated with inflammatory bowel diseases. Peptides 60:102–106. doi:10.1016/j.peptides.2014.08.005 CrossRefPubMed

Sukhtankar DD, Zaveri NT, Husbands SM, Ko M-C (2013) Effects of spinally administered bifunctional nociceptin/orphanin fq peptide receptor/-Opioid receptor ligands in mouse models of neuropathic and inflammatory pain. J Pharmacol Exp Ther 346:11–22. doi:10.1124/jpet.113.203984 CrossRefPubMedPubMedCentral

Sun J, Yang T, Wang P et al (2014) Activation of cold-sensing transient receptor potential melastatin subtype 8 antagonizes vasoconstriction and hypertension through attenuating RhoA/Rho kinase pathway. Hypertension 63(6):1354–1363. doi:10.1161/HYPERTENSIONAHA.113.02573 CrossRefPubMed

Tajti J, Szok D, Majlath Z et al (2015) Migraine and neuropeptides. Neuropeptides 52:19–30. doi:10.1016/j.npep.2015.03.006 CrossRefPubMed

Tian J-H, Xu W, Fang Y et al (1997) Bidirectional modulatory effect of orphanin FQ on morphine-induced analgesia: antagonism in brain and potentiation in spinal cord of the rat. Br J Pharmacol 120:676–680. doi:10.1038/sj.bjp.0700942 CrossRefPubMedPubMedCentral

Tjølsen A, Berge O-G, Hunskaar S et al (1992) The formalin test: an evaluation of the method. Pain 51:5–17. doi:10.1016/0304-3959(92)90003-T CrossRefPubMed

Torrance N, Ferguson JA, Afolabi E et al (2013) Neuropathic pain in the community: more under-treated than refractory? Pain 154:690–699. doi:10.1016/j.pain.2012.12.022 CrossRefPubMedPubMedCentral

Tzschentke TM, Linz K, Frosch S, Christoph T (2017) Antihyperalgesic, antiallodynic, and antinociceptive effects of cebranopadol, a novel potent nociceptin/orphanin FQ and opioid receptor agonist, after peripheral and central administration in rodent models of neuropathic pain. Pain Pract. doi:10.1111/papr.12558 PubMed

Vitale G, Filaferro M, Micioni Di Bonaventura MV et al (2017) Effects of [Nphe ¹, Arg ¹⁴, Lys ¹⁵] N/OFQ-NH ₂ (UFP-101), a potent NOP receptor antagonist, on molecular, cellular and behavioural alterations associated with chronic mild stress. J Psychopharmacol 31:691–703. doi:10.1177/0269881117691456 CrossRefPubMed

Vogel HG, Vogel WH (1997) Analgesic, anti-inflammatory, and antipyretic activity. Drug discovery and evaluation. Springer, Berlin, pp 360–420CrossRef

Wang JL, Bin ZhuC, Cao XD, Wu GC (1999) Distinct effect of intracerebroventricular and intrathecal injections of nociceptin/orphanin FQ in the rat formalin test. Regul Pept 79:159–163. doi:10.1016/S0167-0115(98)00161-X CrossRefPubMed

Wang L, Peng J, Huang H et al (2015) Simvastatin protects Sertoli cells against cisplatin cytotoxicity through enhanced gap junction intercellular communication. Oncol Rep 34(4):2133–2141. doi:10.3892/or.2015.4192 CrossRefPubMed

Waseem M, Parvez S (2016) Neuroprotective activities of curcumin and quercetin with potential relevance to mitochondrial dysfunction induced by oxaliplatin. Protoplasma 253:417–430. doi:10.1007/s00709-015-0821-6 CrossRefPubMed

Witkin JM, Statnick MA, Rorick-Kehn LM et al (2014) The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence. Pharmacol Ther 141:283–299CrossRefPubMed

Xu XJ, Hao JX, Wiesenfeld-Hallin Z (1996) Nociceptin or antinociceptin: potent spinal antinociceptive effect of orphanin FQ/nociceptin in the rat. NeuroReport 7:2092–2094PubMed

Yamamoto T, Nozaki-Taguchi N, Kimura S (1997a) Analgesic effect of intrathecally administered nociceptin, an opioid receptor-like receptor agonist, in the rat formalin test. Neuroscience 81:249–254. doi:10.1016/S0306-4522(97)00166-8 CrossRefPubMed

Yamamoto T, Nozaki-Taguchi N, Kimura S (1997b) Effects of intrathecally administered nociceptin, an opioid receptor-like1 (ORL1) receptor agonist, on the thermal hyperalgesia induced by unilateral constriction injury to the sciatic nerve in the rat. Neurosci Lett 224:107–110. doi:10.1016/S0304-3940(97)13475-9 CrossRefPubMed

Yashpal K, Coderre TJ (1998) Influence of formalin concentration on the antinociceptive effects of anti-inflammatory drugs in the formalin test in rats: separate mechanisms underlying the nociceptive effects of low-and high-concentration formalin. Eur J Pain 2:63–68. doi:10.1016/S1090-3801(98)90047-7 CrossRefPubMed

Zhang Y, Simpson-Durand CD, Standifer KM (2015) Nociceptin/orphanin FQ peptide receptor antagonist JTC-801 reverses pain and anxiety symptoms in a rat model of post-traumatic stress disorder. Br J Pharmacol 172:571–582. doi:10.1111/bph.12701 CrossRefPubMed

Zhao M, Isami K, Nakamura S et al (2012) Acute cold hypersensitivity characteristically induced by oxaliplatin is caused by the enhanced responsiveness of TRPA1 in mice. Mol Pain 8:55. doi:10.1186/1744-8069-8-55 PubMedPubMedCentral

Zhu CB, Cao XD, Xu SF, Wu GC (1997) Orphanin FQ potentiates formalin-induced pain behavior and antagonizes morphine analgesia in rats. Neurosci Lett 235:37–40. doi:10.1016/S0304-3940(97)00704-0 CrossRefPubMed

Title: Evaluation of cebranopadol, a dually acting nociceptin/orphanin FQ and opioid receptor agonist in mouse models of acute, tonic, and chemotherapy-induced neuropathic pain
Authors: Kinga Sałat
Anna Furgała
Robert Sałat
Publication date: 01-04-2018
Publisher: Springer International Publishing
Published in: Inflammopharmacology / Issue 2/2018
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-017-0405-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Evaluation of cebranopadol, a dually acting nociceptin/orphanin FQ and opioid receptor agonist in mouse models of acute, tonic, and chemotherapy-induced neuropathic pain

Abstract

Background

Methods

Key results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Key results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2018

Carbon monoxide-releasing molecule, CORM-3, modulates alveolar macrophage M1/M2 phenotype in vitro

Curcumin affords neuroprotection and inhibits α-synuclein aggregation in lipopolysaccharide-induced Parkinson’s disease model

The peripheral corticotropin-releasing factor (CRF)-induced analgesic effect on somatic pain sensitivity in conscious rats: involving CRF, opioid and glucocorticoid receptors

The effects of β-d-mannuronic acid (M2000), as a novel NSAID, on COX1 and COX2 activities and gene expression in ankylosing spondylitis patients and the murine monocyte/macrophage, J774 cell line

Diethylcarbamazine attenuates the expression of pro-fibrogenic markers and hepatic stellate cells activation in carbon tetrachloride-induced liver fibrosis

Acid-gastric antisecretory effect of the ethanolic extract from Arctium lappa L. root: role of H+, K+-ATPase, Ca2+ influx and the cholinergic pathway