Disease/Model | Species and Strain | Sex | Start Age or Size | Injection Site | Antagonist and Dose | Injection Regimen | Outcomes | References |
---|---|---|---|---|---|---|---|---|
Focal cerebral ischemia and excitotoxic brain injury | C57/SV129 mice | M | 25–30 g | i.c.v. | 3 mM oATP, 30 µM or 10 mM PPADS, or 2 mM KN-62 | 1 µl before and 30 min after MCAO and 0.5 µl before methanoglutamate infusion | Antagonists did not affect ischemic or excitotoxic cell death | Le Feuvre et al., 2003 |
Focal cerebral ischemia | Wistar rats | M | 270–290 g | i.p. | 10 and 100 mg/kg Reactive Blue 2 | 5 min after MCAO | Improved neurologic score and reduced infarct volume | Melani et al., 2006 |
Focal cerebral ischemia | Wistar rats | M | 260–300 g | i.c.v. | 100 mM oATP | 2 µl 60 min after onset of MCAO | Exacerbated behavioral dysfunction and ischemic neural injury | Yanagisawa et al., 2008 |
Focal cerebral ischemia | Wistar rats | M | 270–300 g | i.p. | 30 mg/kg BBG | Every 12 hours for 3 days beginning 30 min after MCAO | Reduced histologic brain damage and neurologic score | Arbeloa et al., 2012 |
Focal cerebral ischemia | C57BL/6 and Balb/c mice | M | 20–28 g | i.v. | 35 mg/kg BBG | Daily for 3 days after MCAO | Increased endogenous ciliary neurotrophic factor but no effect on histologic brain damage | Kang et al., 2013 |
Global cerebral ischemia/reperfusion | Sprague-Dawley rats | M | 260–320 g | i.c.v. | 10 µg of BBG, 1 µg of oATP, or 3 µg of A438079 | 2 µl at 0.5 µl/min 10 min before four-vessel occlusion | Reduced neuron death, neuronal DNA cleavage, glial activation, hippocampal cytokine overexpression, and behavioral deficits and improved survival rate | Chu et al., 2012 |
Anoxia-induced brain injury | Sprague-Dawley rats | N.S. | 2–3 weeks | i.p. | 10 mM oATP | 100 µl 1 hour before anoxia-induced brain ischemia and reperfusion injury | Inhibited whole-brain aquaporin 4 downregulation | Lee et al., 2008b |
Subarachnoid hemorrhage | Sprague-Dawley rats | M | 280–320 g | i.p. | 30 mg/kg BBG | 0.5, 24, and 48 hours after subarachnoid hemorrhage | Improved neurobehavioral functions, reduced brain edema, subcortical neuronal apoptosis, p38 MAPK activation and cleaved caspase-3, and increased Bcl-2 | Chen et al., 2013a |
Subarachnoid hemorrhage | Sprague-Dawley rats | M | 280–320 g | i.p. | 5, 30, or 100 mg/kg BBG | 30 min after subarachnoid hemorrhage | 30, but not 5 or 100, mg/kg improved neurologic score and brain edema, and decreased caspase-1, IL-1β, IL-18 and neutrophil infiltration | Chen et al., 2013b |
Brain trauma | Sprague-Dawley rats | M | Adult | Brain (cortex) | 2 mm3 foam soaked in 1 mM suramin | After corticectomy into surgery site | Reduced MCP-1 expression | Panenka et al., 2001 |
Mechanical injury-induced astrogliosis | Wistar rats | M | 280–320 g | Brain (nucleus accumbens) | 0.03 nmol PPADS | 1 µl at 12 µl/h 15 min before or with agonists | Reduced injury- and agonist-induced astrocyte activation | Franke et al., 2003 |
Mechanical injury- induced microglial activation | Wistar rats | M | 280–320 g | Brain (nucleus accumbens) | 30 pmol of PPADS or 1 pmol of BBG | 1 µl at a rate of 12 µl/h before P2X agonists | Reduced injury-induced P2X receptor expression and inhibited agonist-induced microglial activation | Franke et al., 2007 |
Spinal cord injury | Sprague-Dawley rats | F | 220–250 g | i.s. | 2 nM oATP and PPADS | 2 µl immediately before or 1 h after weight-drop | Improved functional recovery and reduced cell death | Wang et al., 2004 |
Spinal cord injury | Sprague-Dawley rats | N.S. | Adult | i.v. | 10 or 50 mg/kg BBG | 10–15 min after weight-drop and once daily for the next 2 days | Improved hindlimb motor function recovery and reduced spinal cord tissue loss | Peng et al., 2009 |
Spinal cord injury | Fischer rats | F | 220–250 g | i.s. | 10 mM PPADS or 0.2 mM BBG | 30 min after weight-drop | Did not improve locomotion or secondary histopathological changes after 7 weeks | Marcillo et al., 2012 |
Spinal cord injury | Sprague-Dawley rats | F | 220–250 g | i.v. | 10 or 50 mg/kg BBG | 15 min after weight-drop and then at 24 and 72 hours | Did not improve motor recovery or histopathological outcome after 6 weeks | Marcillo et al., 2012 |
Nerve fusion | Sprague-Dawley rats | F | N.S. | Nerve bathed directly | 100 µM Brilliant Blue | After sciatic nerve transection and before nerve rejoining | Decreased compound action potential amplitudes and improved behavioral recovery | Rodriguez-Feo et al., 2013 |
Neuropathic pain | Rats | N.S. | N.S. | i.p. | 10–300 µmol/kg A438079 | 7–14 days after spinal nerve ligation | Dose-dependently reversed mechanical allodynia | Nelson et al., 2006 |
Neuropathic pain | Sprague-Dawley rats | M | 200–300 g | i.p. or p.o. | 4–105 (i.p.) or 142 mg/kg (p.o.) A740003 | 2 weeks after nerve ligation/constriction or vincristine infusion | Dose-dependently attenuated mechanical allodynia in all models | Honore et al., 2006 |
Neuropathic pain | Sprague-Dawley rats | M | 250–400 g | i.p. or i.v. | 10–300 µmol/kg A438079 | 2 weeks after nerve ligation/constriction or vincristine infusion | Dose-dependently attenuated mechanical allodynia in all models (i.p.) and reduced activity of spinal neurons after spinal nerve ligation (i.v.) | McGaraughty et al., 2007 |
Neuropathic pain | C57BL/6 mice | N.S. | 8 weeks | i.p.l. | 4 mg/kg oATP | Daily, starting day of sciatic nerve constriction | Reduced hyperalgesia | Fulgenzi et al., 2008 |
Neuropathic pain | Sprague-Dawley rats | M | 200–250 g | s.c. | 30 mg/kg AACBA | 22–24 days after spinal nerve ligation | Did not alter mechanical hypersensitivity | Broom et al., 2008 |
Neuropathic pain | Rats | N.S. | N.S. | i.p. or p.o. | 10–100 (i.p.) or 100 µmol/kg (p.o.) Compound 53 | After spinal nerve ligation, once (i.p.) or twice daily for 4 days (p.o.) before testing | Reduced tactile allodynia | Perez-Medrano et al., 2009 |
Neuropathic pain | Wistar rats | M | 250–350 g | i.p. | 6.25–50 mg/kg PPADS or 1–100 mg/kg BBG | 7 days after partial ligation of sciatic nerve | Slightly attenuated mechanical allodynia at lower doses | Andó et al., 2010 |
Neuropathic pain | Sprague-Dawley rats | N.S. | 180–220 g | i.t. | 10 µM BBG | 10 µl daily for 14 days starting right after chronic constriction of sciatic nerve | Partially attenuated mechanical allodynia and thermal hypersensitivity | He et al., 2012 |
Neuropathic pain | Sprague-Dawley rats | M | 180–350 g | i.t. | 300 µM oATP or 20 µM BBG | 5 µl/min for 4 min 0.5 hours before tetanic stimulation of sciatic nerve | Prevented spinal long-term potentiation and reduced mechanical allodynia; BBG also inhibited the upregulation of microglial P2X7 and expression of Iba-1, phosphorylated p38, IL-1β and GluR1 | Chu et al., 2010 |
Neuropathic pain | Sprague-Dawley rats | N.S. | N.S. | s.c. | 3, 30, or 100 mg/kg JNJ-47965567 | Once after spinal nerve ligation | 30, but not 3 or 100, mg⋅kg−1 reduced mechanical allodynia after 30–60 min | Bhattacharya et al., 2013 |
Orofacial pain | Sprague-Dawley rats | M | 200–250 g | i.t. | 35 µg of A438079 | Immediately after CCI of the infraorbital nerve | Inhibited tactile allodynia/ hyperalgesia and prevented TNF-α upregulation in trigeminal sensory nuclear complex | Ito et al., 2013 |
Acute thermal nociception | Sprague-Dawley rats | M | 200–300 g | i.p. | 142 mg/kg A740003 | 30 min before hot-plate test | Did not affect paw withdrawal latencies in response to heat | Honore et al., 2006 |
Acute thermal nociception | Wistar rats | M | 170–300 g | i.p. | 6.25–50 mg/kg PPADS or 3–100 mg/kg BBG | 30 min before hot-plate test | 25 and 50 mg/kg PPADS elevated heat threshold; 10 mg/kg BBG reduced heat threshold | Andó et al., 2010 |
Morphine tolerance | Sprague-Dawley rats | M | 180–350 g | i.t. | 25 mg/kg BBG | 2×/day for 5 days, 30 min before each morphine dose | Reduced tolerance to morphine analgesia | Chen et al., 2012 |
BzATP-induced IL-1β release | Sprague-Dawley rats | M | 280–320 g | s.c. | 30 or 100 mg/kg JNJ-47965567 | 30 min before Bz-ATP | 100, but not 30, mg/kg attenuated IL-1β release from hippocampus | Bhattacharya et al., 2013 |
BzATP; 2′(3′)-O-(4-benzoylbenzoyl) ATP; CCI, chronic constriction injury; GFAP, glial fibrillary acidic protein; Iba-1, ionized calcium-binding adapter molecule 1; IL, interleukin; i.p.l., intraplantar; i.s., intraspinal; MAPK, mitogenactivated protein kinase; MCAO, middle cerebral artery occlusion; MCP-1, monocyte chemoattractant protein-1; N.S., not stated; PKC, protein kinase C; TNF, tumor necrosis factor.