cangrelor and Neuralgia

cangrelor has been researched along with Neuralgia* in 2 studies

Other Studies

2 other study(ies) available for cangrelor and Neuralgia

ArticleYear
Nerve injury-activated microglia engulf myelinated axons in a P2Y12 signaling-dependent manner in the dorsal horn.
    Glia, 2010, Nov-15, Volume: 58, Issue:15

    The mechanisms underlying neuropathic pain are poorly understood. However, several studies have implied a role for reactive microglia located in the dorsal horn in neuropathic pain. To clarify the roles of activated microglia in neuropathic pain, we investigated the interactions among microglia and other neural components in the dorsal horn using electron microscopy. Microglia were more abundantly localized in layers II-III of the dorsal horn than in other areas, and some of them adhered to and engulfed both injured and uninjured myelinated axons. This microglial engulfment was rarely observed in the normal dorsal horn, and the number of microglia attached to myelinated axons was markedly increased on postoperative day 7 on the operated side. However, after blocking the P2Y12 ATP receptor in microglia by intrathecal administration of its antagonist, AR-C69931MX, the increase in the number of microglia attached to myelinated axons, as well as the development of tactile allodynia, were markedly suppressed, although the number of activated microglia did not change remarkably. These results indicate that engulfment of myelinated axons by activated microglia via P2Y12 signaling in the dorsal horn may be a critical event in the pathogenesis of neuropathic pain.

    Topics: Adenosine Monophosphate; Animals; Calcium-Binding Proteins; Cell Proliferation; Disease Models, Animal; Functional Laterality; Gene Expression Regulation; Hyperalgesia; Male; Microfilament Proteins; Microglia; Microscopy, Immunoelectron; Nerve Fibers, Myelinated; Neuralgia; Posterior Horn Cells; Purinergic P2Y Receptor Antagonists; Rats; Rats, Wistar; Receptors, Purinergic P2Y12; Signal Transduction; Spinal Cord; Spinal Nerves

2010
P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury.
    The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008, May-07, Volume: 28, Issue:19

    Extracellular nucleotides have been implicated as signaling molecules used by microglia to sense adverse physiological conditions, such as neuronal damage. They act through purinoceptors, especially the G-protein-coupled P2Y receptor P2Y(12)R. Emerging evidence has indicated that activated spinal microglia responding to nerve injury are key cellular intermediaries in the resulting highly debilitating chronic pain state, namely neuropathic pain. However, the role of microglial P2Y(12)Rs in neuropathic pain remains unknown. Here, we show that the level of P2Y(12)R mRNA expression was markedly increased in the spinal cord ipsilateral to the nerve injury and that this expression was highly restricted to ionized binding calcium adapter molecule 1-positive microglia. An increase in the immunofluorescence of P2Y(12)R protein in the ipsilateral spinal cord was also observed after nerve injury, and P2Y(12)R-positive cells were double labeled with the microglial marker OX-42. Blocking spinal P2Y(12)R by the intrathecal administration of its antagonist AR-C69931MX prevented the development of tactile allodynia (pain hypersensitivity to innocuous stimuli), a hallmark of neuropathic pain syndrome. Furthermore, mice lacking P2ry(12) (P2ry(12)(-/-)) displayed impaired tactile allodynia after nerve injury without any change in basal mechanical sensitivity. Moreover, a single intrathecal administration of AR-C69931MX or oral administration of clopidogrel (a P2Y(12)R blocker clinically in use) to nerve-injured rats produced a striking alleviation of existing tactile allodynia. Together, our findings indicate that activation of P2Y(12)Rs in spinal microglia may be a critical event in the pathogenesis of neuropathic pain and suggest that blocking microglial P2Y(12)R might be a viable therapeutic strategy for treating neuropathic pain.

    Topics: Adenosine Monophosphate; Administration, Oral; Animals; Clopidogrel; Hyperesthesia; Injections, Spinal; Male; Membrane Proteins; Mice; Mice, Knockout; Microglia; Neuralgia; Purinergic P2 Receptor Antagonists; Rats; Rats, Wistar; Receptors, Purinergic P2; Receptors, Purinergic P2Y12; Spinal Cord; Spinal Nerves; Ticlopidine; Up-Regulation

2008