Cellular and molecular neurobiology
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Cell. Mol. Neurobiol. · Apr 2013
Capsaicin up-regulates protease-activated receptor-4 mRNA and protein in primary cultured dorsal root ganglion neurons.
Previous study has shown that there is a functional link between the transient receptor potential vanilloid type 1 (TRPV1) receptor and protease-activated receptor-4 (PAR4) in modulation of inflammation and pain. Capsaicin activation of TRPV1 is involved in enhancement of the expression of TRPV1 in mRNA and protein in dorsal root ganglion (DRG) in vivo. Whether capsaicin could influence expression of PAR4 in primary sensory neurons remains unknown. ⋯ Consistent with the involvement of PKA in the modulation of PAR4 expression, this evoked expression both at mRNA and protein levels was significantly inhibited after PKA was inhibited by pre-incubation with PKI14-22. Taken together, these results provide evidence that TRPV1 activation significantly increases the expression of PAR4 mRNA and protein levels in primary cultures of DRG neurons after capsaicin incubation. Effects of capsaicin on PAR4 expression appear to be mediated by cAMP/PKA signal pathways in DRG neurons.
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Cell. Mol. Neurobiol. · Mar 2013
TRPV1 properties in thoracic dorsal root ganglia neurons are modulated by intraperitoneal capsaicin administration in the late phase of type-1 autoimmune diabetes.
Pharmacological therapies in type 1 diabetes for efficient control of glycemia and changes in pain alterations due to diabetic neuropathy are a continuous challenge. Transient receptor potential vanilloid type 1 (TRPV1) from dorsal root ganglia (DRG) neurons is one of the main pharmacological targets in diabetes, and its ligand capsaicin can be a promising compound for blood-glucose control. Our goal is to elucidate the effect of intraperitoneal (i.p.) capsaicin administration in type 1 diabetic mice against TRPV1 receptors from pancreatic DRG primary afferent neurons. ⋯ A TRPV1 hypoalgesia profile was observed in late-phase diabetes, which was partly reversed to normoalgesic profile upon capsaicin i.p. administration. According to the soma dimensions of the thoracic DRG neurons, a detailed analysis of the TRPV1 expression upon capsaicin i.p. treatment was done, and the proportion of large A-fiber neurons expressing TRPV1 increased in dTg capsaicin-treated mice. In conclusion, the benefits of low-dose capsaicin intraperitoneal treatment in late-phase type-1 diabetes should be further exploited.
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Cell. Mol. Neurobiol. · Mar 2013
Activation of different signals identified with glia cells contribute to the progression of hyperalgesia.
Hyperalgesia results from a decreased pain threshold, often subsequent to peripheral tissue damage. Recent reports revealed several promising mechanisms of hyperalgesia, but many issues remain unclear. The glial activation accompanying inflammation of neurotransmission in the spinal cord might be related to the initiation and maintenance of hyperalgesia. ⋯ The present results revealed that microglial activation resulting from the release of the phosphatase p38-MAPK, the transcription factor NF-κB, and BDNF contributes to the early stage of inflammatory pain. Astrocyte activation accompanying JNK activation contributes to subsequent hyperalgesia. Activation of different signals identified with glia cells is thought to contribute to the progression of hyperalgesia, which represents an applicable finding for the treatment of hyperalgesia.
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Cell. Mol. Neurobiol. · Jan 2013
The reverse roles of transient receptor potential canonical channel-3 and -6 in neuronal death following pilocarpine-induced status epilepticus.
Transient receptor potential canonical channel (TRPC) is a nonselective cation channel permeable to Ca(2+), which is expressed in many cell types, including neurons. However, the alterations in TRPC receptor expressions in response to status epilepticus (SE) have not been explored. Therefore, the present study was designated to elucidate the roles of TRPC3 and TRPC6 in neuronal death following SE. ⋯ Hyperforin (a TRPC6 activator) effectively prevented down-regulation of neuronal TRPC6 expression induced by SE. In addition, both Pyr3 and hyperforin effectively protected neuronal damages from SE. Therefore, the present study yields novel information regarding the role of TRPC3 and 6 in epileptogenic insults and suggests that TRPC 3 and 6 may be involved in neurodegeneration following SE.
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Cell. Mol. Neurobiol. · Jan 2013
An evaluation of the antinociceptive effects of Phα1β, a neurotoxin from the spider Phoneutria nigriventer, and ω-conotoxin MVIIA, a cone snail Conus magus toxin, in rat model of inflammatory and neuropathic pain.
Voltage-sensitive calcium channels (VSCCs) underlie cell excitability and are involved in the mechanisms that generate and maintain neuropathic and inflammatory pain. We evaluated in rats the effects of two VSCC blockers, ω-conotoxin MVIIA and Phα1β, in models of inflammatory and neuropathic pain induced with complete Freund's adjuvant (CFA) and chronic constrictive injury (CCI), respectively. We also evaluated the effects of the toxins on capsaicin-induced Ca(2+) influx in dorsal root ganglion (DRG) neurons obtained from rats exposed to both models of pain. ⋯ The management of chronic inflammatory and neuropathic pain is still a major challenge for clinicians. Phα1β, a reversible inhibitor of VSCCs with a preference for N-type Ca(2+) channels, has potential as a novel therapeutic agent for inflammatory and neuropathic pain. Clinical studies are necessary to establish the role of Phα1β in the treatment of chronic pain.