Antagonism of P2X7 in rodent models of compound-induced inflammation
| Disease/Model | Species and Strain | Sex | Start Age or Size | Injection Site | Antagonist and Dose | Injection Regimen | Outcomes | References |
|---|---|---|---|---|---|---|---|---|
| Formalin-induced pain | Sprague-Dawley rats | M | 100–200 g | s.c., hindpaw | 50–500 nmol of suramin or 5–500 nmol of PPADS | Coadministered with formalin or formalin/ATP | Dose-dependently inhibited amplification of the formalin response (flinching) by ATP but not to formalin alone | Sawynok and Reid, 1997 |
| Formalin-induced pain | Sprague-Dawley rats | M | 250–400 g | i.p. | 30–300 µmol/kg A438079 | After injecting formalin into hind paw | Dose-dependently attenuated nocifensive behaviors (paw flinching, licking, guarding) | McGaraughty et al., 2007 |
| Formalin-induced pain | BALB/cJ mice | N.S. | 6–8 weeks | s.c. | 300 µmol/kg A438079 | 30 min before formalin injection | Attenuated nocifensive behaviors (licking, biting) | Hansen et al., 2011 |
| Acetic acid-induced visceral pain | C57BL/6 mice | N.S. | 8 weeks | i.p. | 4 mg/kg oATP | 30 min before inducing visceral pain | Reduced writhing responses | Fulgenzi et al., 2008 |
| LPS-induced inflammation | Wistar rats | M | 280–320 g | i.p. | 5, 25, or 100 mg/kg suramin; 5 or 25 mg/kg PPADS; or 40 or 100 mg/kg BBG | 5 min before i.p. LPS injection | Attenuated fever (all), increased plasma IL-1β and IL-6 (PPADS, BBG), and increased plasma TNF-α (BBG) | Gourine et al., 2005 |
| LPS-induced inflammation | Wistar rats | M | 200–300 g | s.c. | 1–30 mg/kg AACBA | 1 hour before i.p. LPS injection | Dose-dependently reduced plasma IL-6 release | Broom et al., 2008 |
| LPS-induced inflammation | Wistar rats | M | 200–300 g | i.p. | 25 mg/kg PPADS, 100 mg/kg BBG, or 0.9 mg/kg oATP | 30 min (PPADS and BBG) or 2 hours (oATP) before i.p. LPS injection | Reduced hippocampal IL-1β release; BBG also reduced basal release | Csölle and Sperlágh, 2010 |
| LPS-induced inflammation | C57Bl/6J mice | M | 2–3 months | i.p. | 100 mg/kg BBG, 0.9 mg/kg oATP | 30 min (BBG) or 2 hours (oATP) before i.p. LPS injection | Reduced hippocampal IL-1β release; also reduced basal release | Csölle and Sperlágh, 2010 |
| LPS-induced inflammation | C57BL/6 mice | N.S. | N.S.. | i.p. | 100 µmol/kg A438079 | 1 hour before i.p. LPS injection | Impaired body temperature increase | Barberà-̀Cremades et al., 2012 |
| LPS-induced CNS inflammation | Sprague-Dawley rats | M | 240–260 g | i.c.v. | 1 µM oATP | 30 min before striatal LPS injection | Reduced activated microglia, phosphorylation of p38 MAPK, iNOS production, nitration of proteins, lipid peroxidation, oxidative DNA damage, and caspase-3 activation and increased neuronal survival | Choi et al., 2007 |
| LPS-induced CNS inflammation | Wistar rats | M | N.S. | i.t. | 50 µg of oATP or 50 µg of A438079 | With or without LPS 24 h after 1st i.t. LPS injection | Attenuated mechanical hyperalgesia and prevented phosphorylation of p38 MAPK in microglia | Clark et al., 2010 |
| Carrageenan-induced inflammation | Wistar rats | M | ∼250 g | i.p.l., p.o., or i.v. | 50–200 μM oATP | 3 hours after i.p.l. carrageenan injection | Reduced thermal hyperalgesia (all routes), expression of chemokines and P2X7, and macrophage infiltrates (i.p.l, i.v.) | Fulgenzi et al., 2005 |
| Carrageenan-induced inflammation | Sprague-Dawley rats | M | 200–300 g | i.p. | 14–142 mg/kg A740003 | 90 min after i.p.l. carrageenan injection | Dose-dependently reduced thermal hyperalgesia and paw edema | Honore et al., 2006 |
| Carrageenan-induced inflammation | Sprague-Dawley rats | M | 200–250 g | s.c. | 3–100 mg/kg AACBA | 30 min before (prophylactic) or 1–1.5 hours after (therapeutic) i.p.l. carrageenan injection | Prophylactically and therapeutically reduced mechanical hypersensitivity, and therapeutically reduced paw swelling | Broom et al., 2008 |
| Carrageenan-induced inflammation | Albino Wistar rats | M | 200–250 g | TMJ | 100, 300, and 900 µg of A438079 | Coinjected with carrageenan | Did not alter TMJ hyperalgesia | Teixeira et al., 2010a |
| Carrageenan-induced inflammation | Wistar rats | M | 200–250 g | s.c., hindpaw | 0.5, 2, or 6 µg/paw oATP or 100 or 300 µg/paw A438079 | Coinjected with carrageenan | Reduced hyperalgesia and the concentration of TNF-α, IL-6, and CINC, but not IL-1β, in hindpaw | Teixeira et al., 2010b |
| MO-induced inflammation | Sprague-Dawley rats | M | 275–420 g | i.t. | 1 µM BBG or 100 µM oATP | Continuous superfusion over MDH for 2 hours | Attenuated MDH central sensitization | Itoh et al., 2011 |
| CO-induced irritant contact dermatitis | Swiss mice | M | 6–8 weeks | i.p. | 80 µmol/kg A438079 | 2 hours after CO application | Reduced neutrophil infiltration, myeloperoxidase levels, IL-1β, Gr1+ cell recruitment, dendritic cells, and macrophages and decreased ear edema | Da Silva et al., 2013 |
| Venom-induced pain and inflammation | Sprague-Dawley rats | M | 250–300 g | i.t. | 0.1, 1, or 10 µg of A438079 | 10 min before venom injection | Dose-dependently inhibited spontaneous flinching and mechanical allodynia but not edema | Zhou et al., 2012 |
CINC, cytokine-induced neutrophil chemoattractant 1; CNS, central nervous system; CO, croton oil; IL, interleukin; iNOS, inducible nitric-oxide synthase; i.p.l., intraplantar; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MDH, medullary dorsal horn; MO, mustard oil; N.S., not stated; TMJ, temporomandibular joint; TNF, tumor necrosis factor.