Regulatory mechanisms and therapeutic potential of microglial inhibitors in neuropathic pain and morphine tolerance.

Microglia are important cells involved in the regulation of neuropathic pain (NPP) and morphine tolerance. Information on their plasticity and polarity has been elucidated after determining their physiological structure, but there is still much to learn about the role of this type of cell in NPP and morphine tolerance. Microglia mediate multiple functions in health and disease by controlling damage in the central nervous system (CNS) and endogenous immune responses to disease. Microglial activation can result in altered opioid system activity, and NPP is characterized by resistance to morphine. Here we investigate the regulatory mechanisms of microglia and review the potential of microglial inhibitors for modulating NPP and morphine tolerance. Targeted inhibition of glial activation is a clinically promising approach to the treatment of NPP and the prevention of morphine tolerance. Finally, we suggest directions for future research on microglial inhibitors.

Effect of tetramethylpyrazine on acute nociception mediated by signaling of P2X receptor activation in rat.

Tetramethylpyrazine (TMP) has been used in traditional Chinese medicine as an analgesic for dysmenorrhea. In the present study, we try to investigate the effects of TMP on acute nociception mediated by P2X receptor activation of rat hindpaw and the membrane depolarization of rat dorsal root ganglion (DRG) neurons induced by P2X receptor agonists. The subcutaneous administration of TMP (0.1-10 mmol) into rat hindpaw in a dose-dependent manner decreased acute paw flinching responses mediated by adenosine 5'-triphosphate (ATP, 1000 nmol) or alpha,beta-methylene ATP (alpha,beta-meATP, 600 nmol). The subcutaneous administration of TMP (5 or 10 mmol) into rat hindpaw inhibited significantly the first phase of nociceptive behaviors induced by 5% formalin and attenuated slightly the second phase of nociceptive behaviors induced by 5% formalin. The subcutaneous administration of TMP (10 mmol) into rat hindpaw reduced the nociceptive responses induced by alpha,beta-meATP (200 nmol) co-injected with Prostaglandin E2 (PGE2), 5 micromol). The membrane depolarization induced by ATP (200 micromol) or alpha,beta-meATP (50 micromol) in DRG neurons was inhibited by TMP (300 micromol). The data suggest that the antinociceptive effect of TMP is involved in blocking the signaling of P2X3 receptor activation in rat.