McGaraughty_2007_Neurosci_146_1817

Reference

Title : P2X7-related modulation of pathological nociception in rats - McGaraughty_2007_Neurosci_146_1817
Author(s) : McGaraughty S , Chu KL , Namovic MT , Donnelly-Roberts D , Harris RR , Zhang XF , Shieh CC , Wismer CT , Zhu CZ , Gauvin DM , Fabiyi AC , Honore P , Gregg RJ , Kort ME , Nelson DW , Carroll WA , Marsh K , Faltynek CR , Jarvis MF
Ref : Neuroscience , 146 :1817 , 2007
Abstract :

Growing evidence supports a role for the immune system in the induction and maintenance of chronic pain. ATP is a key neurotransmitter in this process. Recent studies demonstrate that the glial ATP receptor, P2X7, contributes to the modulation of pathological pain. To further delineate the endogenous mechanisms that are involved in P2X7-related antinociception, we utilized a selective P2X7 receptor antagonist, A-438079, in a series of in vivo and in vitro experiments. Injection of A-438079 (10-300 micromol/kg, i.p.) was anti-allodynic in three different rat models of neuropathic pain and it attenuated formalin-induced nocifensive behaviors. Using in vivo electrophysiology, A-438079 (80 micromol/kg, i.v.) reduced noxious and innocuous evoked activity of different classes of spinal neurons (low threshold, nociceptive specific, wide dynamic range) in neuropathic rats. The effects of A-438079 on evoked firing were diminished or absent in sham rats. Spontaneous activity of all classes of spinal neurons was also significantly reduced by A-438079 in neuropathic but not sham rats. In vitro, A-438079 (1 microM) blocked agonist-induced (2,3-O-(4-benzoylbenzoyl)-ATP, 30 microM) current in non-neuronal cells taken from the vicinity of the dorsal root ganglia. Furthermore, A-438079 dose-dependently (0.3-3 microM) decreased the quantity of the cytokine, interleukin-1beta, released from peripheral macrophages. Thus, ATP, acting through the P2X7 receptor, exerts a wide-ranging influence on spinal neuronal activity following a chronic injury. Antagonism of the P2X7 receptor can in turn modulate central sensitization and produce antinociception in animal models of pathological pain. These effects are likely mediated through immuno-neural interactions that affect the release of endogenous cytokines.

PubMedSearch : McGaraughty_2007_Neurosci_146_1817
PubMedID: 17478048

Related information

Citations formats

McGaraughty S, Chu KL, Namovic MT, Donnelly-Roberts D, Harris RR, Zhang XF, Shieh CC, Wismer CT, Zhu CZ, Gauvin DM, Fabiyi AC, Honore P, Gregg RJ, Kort ME, Nelson DW, Carroll WA, Marsh K, Faltynek CR, Jarvis MF (2007)
P2X7-related modulation of pathological nociception in rats
Neuroscience 146 :1817

McGaraughty S, Chu KL, Namovic MT, Donnelly-Roberts D, Harris RR, Zhang XF, Shieh CC, Wismer CT, Zhu CZ, Gauvin DM, Fabiyi AC, Honore P, Gregg RJ, Kort ME, Nelson DW, Carroll WA, Marsh K, Faltynek CR, Jarvis MF (2007)
Neuroscience 146 :1817