Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical and thermal allodynia after burn injury
The primary complaint of burn victims is an intense, often devastating spontaneous pain, with persistence of mechanical and thermal allodynia. The transient receptor potential channels, TRPV1 and TRPA1, are expressed by a subset of nociceptive sensory neurons and contribute to inflammatory hypersensitivity. Although their function in the periphery is well known, a role for these TRP channels in central pain mechanisms is less well defined. Lipid agonists of TRPV1 are released from peripheral tissues via enzymatic oxidation after burn injury; however, it is not known if burn injury triggers the release of oxidized lipids in...
Source: Molecular Pain - July 11, 2016 Category: Molecular Biology Authors: Green, D. P., Ruparel, S., Gao, X., Ruparel, N., Patil, M., Akopian, A., Hargreaves, K. M. Tags: Research Article Source Type: research

EXPRESS: Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injury
(Source: Molecular Pain)
Source: Molecular Pain - July 11, 2016 Category: Molecular Biology Authors: Green, D., Ruparel, S., Gao, X., Ruparel, N., Patil, M., Akopian, A., Hargreaves, K. Tags: Articles Source Type: research

Histone hyperacetylation modulates spinal type II metabotropic glutamate receptor alleviating stress-induced visceral hypersensitivity in female rats
Stress is often a trigger to exacerbate chronic pain including visceral hypersensitivity associated with irritable bowel syndrome, a female predominant functional bowel disorder. Epigenetic mechanisms that mediate stress responses are a potential target to interfere with visceral pain. The purpose of this study was to examine the effect of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, on visceral hypersensitivity induced by a subchronic stressor in female rats and to investigate the involvement of spinal glutamate receptors. Three daily sessions of forced swim induced visceral hypersensitivity. Intrathe...
Source: Molecular Pain - July 4, 2016 Category: Molecular Biology Authors: Cao, D.-Y., Bai, G., Ji, Y., Karpowicz, J., Traub, R. J. Tags: Research Article Source Type: research

Voltage-dependent sodium (NaV) channels in group IV sensory afferents
Patients with intermittent claudication suffer from both muscle pain and an exacerbated exercise pressor reflex. Excitability of the group III and group IV afferent fibers mediating these functions is controlled in part by voltage-dependent sodium (NaV) channels. We previously found tetrodotoxin-resistant NaV1.8 channels to be the primary type in muscle afferent somata. However, action potentials in group III and IV afferent axons are blocked by TTX, supporting a minimal role of NaV1.8 channels. To address these apparent differences in NaV channel expression between axon and soma, we used immunohistochemistry to identify t...
Source: Molecular Pain - July 4, 2016 Category: Molecular Biology Authors: Ramachandra, R., Elmslie, K. S. Tags: Research Article Source Type: research

F-actin links Epac-PKC signaling to purinergic P2X3 receptor sensitization in dorsal root ganglia following inflammation
Sensitization of purinergic P2X3 receptors (P2X3Rs) contributes to the production of exaggerated nociceptive responses following inflammatory injury. We showed previously that prostaglandin E2 (PGE2) potentiates P2X3R-mediated ATP currents in dorsal root ganglion neurons isolated from both control and complete Freund’s adjuvant-induced inflamed rats. PGE2 potentiation of ATP currents depends only on PKA signaling in control neurons, but it depends on both PKA and PKC signaling in inflamed neurons. We further found that inflammation evokes an increase in exchange proteins directly activated by cAMP (Epacs) in dorsal r...
Source: Molecular Pain - July 4, 2016 Category: Molecular Biology Authors: Gu, Y., Wang, C., Li, G., Huang, L.-Y. M. Tags: Research Article Source Type: research

EXPRESS: Histone hyperacetylation modulates spinal type II metabotropic glutamate receptor alleviating stress-induced visceral hypersensitivity in female rats
(Source: Molecular Pain)
Source: Molecular Pain - July 4, 2016 Category: Molecular Biology Authors: Cao, D.-Y., Bai, G., Ji, Y., Karpowicz, J. M., Traub, R. J. Tags: Articles Source Type: research

EXPRESS: Voltage-dependent sodium (NaV) channels in group IV sensory afferents
(Source: Molecular Pain)
Source: Molecular Pain - July 4, 2016 Category: Molecular Biology Authors: Ramachandra, R., Elmslie, K. S. Tags: Articles Source Type: research

EXPRESS: F-actin links Epac-PKC signaling to purinergic P2X3 receptors sensitization in dorsal root ganglia following inflammation
(Source: Molecular Pain)
Source: Molecular Pain - July 4, 2016 Category: Molecular Biology Authors: Gu, Y., Wang, C., Li, G., Huang, L.-Y. M. Tags: Articles Source Type: research

Further observations on the behavioral and neural effects of bone marrow stromal cells in rodent pain models
Conclusions Collectively, the present work adds convergent evidence supporting the use of BMSCs in pain control. As PKC activity related to N-methyl-D-aspartate receptor activation is critical in opioid tolerance, these results help to understand the mechanisms of BMSC-produced long-term antihyperalgesia, which requires opioid receptors in rostral ventromedial medulla and apparently lacks the development of tolerance. (Source: Molecular Pain)
Source: Molecular Pain - June 20, 2016 Category: Molecular Biology Authors: Guo, W., Chu, Y.-X., Imai, S., Yang, J.-L., Zou, S., Mohammad, Z., Wei, F., Dubner, R., Ren, K. Tags: Research Article Source Type: research

Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: Mechanisms underlying hypoalgesia in Buruli ulcer
Conclusion Mycolactone induces toxic effects in DRG neurons, leading to impaired nociceptor function, neurite degeneration, and cell death, resembling the cutaneous hypoalgesia and nerve damage in individuals with M. Ulcerans infection. (Source: Molecular Pain)
Source: Molecular Pain - June 19, 2016 Category: Molecular Biology Authors: Anand, U., Sinisi, M., Fox, M., MacQuillan, A., Quick, T., Korchev, Y., Bountra, C., McCarthy, T., Anand, P. Tags: Research Article Source Type: research

Novel CLCN7 mutation identified in a Han Chinese family with autosomal dominant osteopetrosis-2
Osteopetrosis is a heritable bone condition featuring increased bone density due to defective osteoclastic bone resorption. Exome sequencing and Sanger sequencing were conducted in Han Chinese family members, some of whom had typical osteopetrosis, and a novel missense variant c.2350A>T (p.R784W) in the chloride channel 7 gene (CLCN7) was identified. This variant cosegregated with the disorder in the family but was not observed in 800 controls. The data indicate that exome sequencing is a powerful and effective molecular diagnostic tool for detecting mutations in osteopetrosis, which is a genetically and clinically hete...
Source: Molecular Pain - June 19, 2016 Category: Molecular Biology Authors: Deng, H., He, D., Rong, P., Xu, H., Yuan, L., Li, L., Lu, Q., Guo, Y. Tags: Research Article Source Type: research

Characterization of methadone as a {beta}-arrestin-biased {mu}-opioid receptor agonist
Conclusions These results suggest that methadone may, at least partly, produce its pharmacological effect as a β-arrestin-biased µ-opioid receptor agonist, similar to fentanyl, and NMDA receptor blockade is not the main contributor to the pharmacological profile of methadone. (Source: Molecular Pain)
Source: Molecular Pain - June 16, 2016 Category: Molecular Biology Authors: Doi, S., Mori, T., Uzawa, N., Arima, T., Takahashi, T., Uchida, M., Yawata, A., Narita, M., Uezono, Y., Suzuki, T., Narita, M. Tags: Research Article Source Type: research

Estrogen-dependent visceral hypersensitivity following stress in rats: An fMRI study
This study is the first to examine estrogen-stress dependent interactions in response to noxious visceral stimulation using functional MRI. Future studies that include other control groups and larger sample sizes are needed to fully understand the interactions between sex hormones, stress, and noxious stimulation on brain activity. (Source: Molecular Pain)
Source: Molecular Pain - June 16, 2016 Category: Molecular Biology Authors: Hubbard, C. S., Karpowicz, J. M., Furman, A. J., da Silva, J. T., Seminowicz, D. A., Traub, R. J. Tags: Research Article Source Type: research

Dopaminergic Modulation of Excitatory Transmission in the Anterior Cingulate Cortex of Adult Mice
Dopamine (DA) possesses potent neuromodulatory properties in the central nervous system. In the anterior cingulate cortex, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) are key ion channels in mediating nerve injury induced long-term potentiation (LTP) and chronic pain phenotype. In the present study, we reported the effects of DA on glutamate mediated excitatory post-synaptic currents (EPSCs) in pyramidal neurons of layer II/III of the ACC in adult mice. Bath application of DA (50 μM) caused a significant, rapid and reversible inhibition of evoked EPSCs (eEPSC). This inhibitory effect is...
Source: Molecular Pain - June 16, 2016 Category: Molecular Biology Authors: Darvish-Ghane, S., Yamanaka, M., Zhuo, M. Tags: Research Article Source Type: research

Methylcobalamin ameliorates neuropathic pain induced by vincristine in rats: Effect on loss of peripheral nerve fibers and imbalance of cytokines in the spinal dorsal horn
Conclusions Methylcobalamin attenuated vincrinstine-induced neuropathic pain, which was accompanied by inhibition of intraepidermal nerve fibers loss and mitochondria impairment. Inhibiting the activation of NADPH oxidase and the downstream NF-B pathway, resulting in the rebalancing of proinflammatory and anti-inflammatory cytokines in the spinal dorsal horn might also be involved. These findings might provide potential target for preventing vincristine-induced neuropathic pain. (Source: Molecular Pain)
Source: Molecular Pain - June 14, 2016 Category: Molecular Biology Authors: Xu, J., Wang, W., Zhong, X.-X., Feng, Y.-W., Wei, X.-H., Liu, X.-G. Tags: Research Article Source Type: research