Neuroscience bulletin
-
Neuroscience bulletin · Apr 2012
Increased function of the TRPV1 channel in small sensory neurons after local inflammation or in vitro exposure to the pro-inflammatory cytokine GRO/KC.
Inflammation at the level of the sensory dorsal root ganglia (DRGs) leads to robust mechanical pain behavior and the local inflammation has direct excitatory effects on sensory neurons including small, primarily nociceptive, neurons. These neurons express the transient receptor potential vanilloid-1 (TRPV1) channel, which integrates multiple signals of pain and inflammation. The aim of this study was to characterize the regulation of the TRPV1 channel by local DRG inflammation and by growth-related oncogene (GRO/KC, systemic name: CXCL1), a cytokine known to be upregulated in inflamed DRGs. ⋯ Function of the TRPV1 channel is enhanced by DRG inflammation and these effects are preserved in vitro during short-term culture. The effects (decreased tachyphylaxis) are mimicked by incubation with GRO/KC, which has previously been found to be strongly upregulated in this and other pain models.
-
Neuroscience bulletin · Apr 2012
Chemokine signaling involving chemokine (C-C motif) ligand 2 plays a role in descending pain facilitation.
Despite accumulating evidence on a role of immune cells and their associated chemicals in mechanisms of pain, few studies have addressed the potential role of chemokines in the descending facilitation of persistent pain. The present study was undertaken to test the hypothesis that the chemokine (C-C motif) ligand 2 (CCL2) (commonly known as monocyte chemoattractant protein-1) signaling in the rostral ventromedial medulla (RVM), a pivotal structure in brainstem pain modulatory circuitry, is involved in descending pain facilitation in rats. ⋯ The IL-1β and CCL2-CCR2 signaling cascades play a role in neuron-glia-cytokine interactions and the descending facilitation of neuropathic pain.
-
Neuroscience bulletin · Apr 2012
Formaldehyde up-regulates TRPV1 through MAPK and PI3K signaling pathways in a rat model of bone cancer pain.
Our previous study showed that tumor tissue-derived formaldehyde at low concentrations plays an important role in bone cancer pain through activating transient receptor potential vanilloid subfamily member 1 (TRPV1). The present study further explored whether this tumor tissue-derived endogenous formaldehyde regulates TRPV1 expression in a rat model of bone cancer pain, and if so, what the possible signal pathways are during the development of this type of pain. ⋯ Formaldehyde at a very low concentration up-regulates TRPV1 expression through mitogen-activated protein kinase and PI3K, but not PKC, signaling pathways. These results further support our previous finding that TRPV1 in peripheral afferents plays a role in bone cancer pain.
-
Neuroscience bulletin · Apr 2012
Effects of a non-selective TRPC channel blocker, SKF-96365, on melittin-induced spontaneous persistent nociception and inflammatory pain hypersensitivity.
Melittin is the main peptide in bee venom and causes both persistent spontaneous nociception and pain hypersensitivity. Our recent studies indicated that both transient receptor potential (TRP) vanilloid receptor 1 (TRPV1) and canonical TRPs (TRPCs) are involved in mediating the melittin-induced activation of different subpopulations of primary nociceptive cells. Here, we further determined whether TRPC channels are involved in melittin-induced inflammatory nociceptive responses in behavioral assays. ⋯ Besides TRPV1, SKF-96365-sensitive TRPC channels might also be involved in the pathophysiological processing of melittin-induced inflammatory pain and hypersensitivity. Therapeutically, SKF-96365 is equally effective in preventing primary thermal and mechanical hyperalgesia as well as persistent spontaneous nociception. However, this drug is likely to be more effective in the relief of thermal hyperalgesia than mechanical hyperalgesia when applied 5 min after establishment of primary afferent activation.
-
Neuroscience bulletin · Apr 2012
Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice.
To investigate the role of oxidative stress in itch-indicative scratching behavior in mice, and furthermore, to define the cellular and molecular mechanisms underlying oxidative stress-mediated itch. ⋯ Oxidative stress by different oxidants induces profound scratching behavior, which is largely histamine- and TRPV1-independent but TRPA1-dependent. Antioxidants and TRPA1 antagonists may be used to treat human itch conditions associated with oxidative stress.