D-serine in the midbrain periaqueductal gray contributes to morphine tolerance in rats
Conclusions Our data indicate that the development of antinociceptive tolerance to morphine is partially mediated by ventrolateral midbrain periaqueductal gray D-serine content, and the activation of the ventrolateral midbrain periaqueductal gray P2X7 receptor is an essential prelude to D-serine release. These results suggest that a cascade involving P2X7 receptor–D-serine–N-methyl-D-aspartate receptor mediated signaling pathway in the supraspinal mechanism of morphine tolerance. (Source: Molecular Pain)
Source: Molecular Pain - May 11, 2016 Category: Molecular Biology Authors: Cao, S., Xiao, Z., Sun, M., Li, Y. Tags: Research Article Source Type: research

Ulinastatin attenuates neuropathic pain induced by L5-VRT via the calcineurin/IL-10 pathway
Previous studies have shown that ulinastatin, an effective inhibitor of the inflammatory response in clinical applications, can attenuate hyperalgesia in rodents. However, the underlying mechanism remains unclear. In the present study, we first examined the change in the calcineurin level, which plays an important role in regulating cytokine release in the nervous system, following lumbar 5 ventral root transection in the rat. Furthermore, we determined whether intraperitoneal (i.p.) injection of ulinastatin attenuated pain behavior via inhibition of the calcineurin-mediated inflammatory response induced by lumbar 5 ventra...
Source: Molecular Pain - May 11, 2016 Category: Molecular Biology Authors: Ouyang, H., Nie, B., Wang, P., Li, Q., Huang, W., Xin, W., Zeng, W., Liu, X. Tags: Research Article Source Type: research

Interleukin-1{beta} overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents
Conclusions Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression. (Source: Molecular Pain)
Source: Molecular Pain - May 11, 2016 Category: Molecular Biology Authors: Gui, W.-S., Wei, X., Mai, C.-L., Murugan, M., Wu, L.-J., Xin, W.-J., Zhou, L.-J., Liu, X.-G. Tags: Research Article Source Type: research

Spinal astrocytic activation contributes to both induction and maintenance of pituitary adenylate cyclase-activating polypeptide type 1 receptor-induced long-lasting mechanical allodynia in mice
Conclusion Our data suggest that spinal astrocytic activation triggered by the PAC1 receptor stimulation contributes to both induction and maintenance of the long-term mechanical allodynia. (Source: Molecular Pain)
Source: Molecular Pain - May 11, 2016 Category: Molecular Biology Authors: Yokai, M., Kurihara, T., Miyata, A. Tags: Research Article Source Type: research

Inefficient constitutive inhibition of P2X3 receptors by brain natriuretic peptide system contributes to sensitization of trigeminal sensory neurons in a genetic mouse model of familial hemiplegic migraine
Conclusions P2X3 receptors on mouse trigeminal ganglion neurons are subjected to contrasting modulation by inhibitory brain natriuretic peptide and facilitatory calcitonin gene-related peptide that both operate via complex intracellular signaling. In the familial hemiplegic migraine type-1 migraine model, the action of calcitonin gene-related peptide appears to prevail over brain natriuretic peptide, thus suggesting that peripheral inhibition of P2X3 receptors becomes insufficient and contributes to trigeminal pain sensitization. (Source: Molecular Pain)
Source: Molecular Pain - May 11, 2016 Category: Molecular Biology Authors: Marchenkova, A., Vilotti, S., Ntamati, N., van den Maagdenberg, A. M., Nistri, A. Tags: Research Article Source Type: research

Reduced acute nociception and chronic pain in Shank2-/- mice
Autism spectrum disorder is a debilitating mental illness and social issue. Autism spectrum disorder patients suffer from social isolation, cognitive deficits, compulsive behavior, and sensory deficits, including hyposensitivity to pain. However, recent studies argued that autism spectrum disorder patients show physiological pain response and, in some cases, even extremely intense pain response to harmless stimulation. Recently, Shank gene family was reported as one of the genetic risk factors of autism spectrum disorder. Thus, in this study, we used Shank2–/– (Shank2 knock-out, KO) mice to investigate the cont...
Source: Molecular Pain - May 3, 2016 Category: Molecular Biology Authors: Ko, H.-G., Oh, S.-B., Zhuo, M., Kaang, B.-K. Tags: Short Report Source Type: research

The brain-derived neurotrophic factor pathway, life stress, and chronic multi-site musculoskeletal pain
Conclusions This study suggests that the BDNF gene marks vulnerability for chronic pain. Although life stress did not alter the impact of BDNF on chronic pain, it seems an independent factor in the onset and persistence of chronic pain. (Source: Molecular Pain)
Source: Molecular Pain - May 3, 2016 Category: Molecular Biology Authors: Generaal, E., Milaneschi, Y., Jansen, R., Elzinga, B. M., Dekker, J., Penninx, B. W. Tags: Research Article Source Type: research

Overexpression of GRK6 attenuates neuropathic pain via suppression of CXCR2 in rat dorsal root ganglion
This study was designed to investigate the role of GRK6 and its interaction with substrate chemokine receptors in dorsal root ganglion (DRG) in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Following induction of CCI, GRK6 expression was significantly downregulated in rat DRGs at L4-L6 segments. Overexpression of GRK6 using lentiviral-mediated production strategy via sciatic nerve injection markedly attenuated mechanical allodynia and thermal hyperalgesia in CCI rats. Overexpression of GRK6 also drastically reversed the hyperexcitability of DRG neurons innervating the hind paw and suppressed...
Source: Molecular Pain - May 3, 2016 Category: Molecular Biology Authors: Zhou, Y., Li, R.-J., Li, M., Liu, X., Zhu, H.-Y., Ju, Z., Miao, X., Xu, G.-Y. Tags: Research Article Source Type: research

Peripheral nerve injury induces loss of nociceptive neuron-specific G{alpha}i-interacting protein in neuropathic pain rat
Conclusion Our results show that GINIP is predominantly expressed by small nonpeptidergic nociceptive neurons and that nerve injury triggers loss of GINIP expression. Signal transduction roles of GINIP may be diverse as it colabeled with various subgroups of nociceptive neurons. Future studies may investigate details of the signaling mechanism engaged by GINIP, as well as the pathophysiological significance of lost expression of GINIP in neuropathic pain. (Source: Molecular Pain)
Source: Molecular Pain - May 3, 2016 Category: Molecular Biology Authors: Liu, Z., Wang, F., Fischer, G., Hogan, Q. H., Yu, H. Tags: Research Article Source Type: research

Comprehensive and differential long-term characterization of the alpha-galactosidase A deficient mouse model of Fabry disease focusing on the sensory system and pain development
Conclusions Mice with alpha-galactosidase A deficiency show age-dependent and distinct deficits of the sensory system. alpha-galactosidase A-deficient mice seem to model human Fabry disease and may be helpful when studying the pathophysiology of Fabry-associated pain. (Source: Molecular Pain)
Source: Molecular Pain - May 3, 2016 Category: Molecular Biology Authors: Üceyler, N., Biko, L., Hose, D., Hofmann, L., Sommer, C. Tags: Research Article Source Type: research

Neuronal cell lines as model dorsal root ganglion neurons: A transcriptomic comparison
Conclusions This paper provides insights into the receptor repertoire expressed in common dorsal root ganglion neuron-derived cell lines compared with whole murine dorsal root ganglions, and illustrates the limits and potentials of these cell lines as tools for neuropharmacological exploration. (Source: Molecular Pain)
Source: Molecular Pain - April 28, 2016 Category: Molecular Biology Authors: Yin, K., Baillie, G. J., Vetter, I. Tags: Research Article Source Type: research

A cell-permeant peptide corresponding to the cUBP domain of USP5 reverses inflammatory and neuropathic pain
Conclusions Our findings reveal a crucial region in the cUBP domain of USP5 that is important for substrate recognition and binding to the III-IV linker of Cav3.2 channels. Targeting the interaction of this region with the Cav3.2 channel can be exploited as the basis for therapeutic intervention into inflammatory and neuropathic pain. (Source: Molecular Pain)
Source: Molecular Pain - April 28, 2016 Category: Molecular Biology Authors: Garcia-Caballero, A., Gadotti, V. M., Chen, L., Zamponi, G. W. Tags: Research Article Source Type: research

Enhanced itch elicited by capsaicin in a chronic itch model
Chronic itch (pruritus) is an important clinical problem. However, the underlying molecular basis has yet to be understood. The Transient Receptor Potential Vanilloid 1 channel is a heat-sensitive cation channel expressed in primary sensory neurons and involved in both thermosensation and pain, but its role in chronic itch remains elusive. Here, we for the first time revealed an increased innervation density of Transient Receptor Potential Vanilloid 1-expressing sensory fibers in the skin afflicted with chronic itch. Further analysis indicated that this phenomenon is due to an expansion of Transient Receptor Potential Vani...
Source: Molecular Pain - April 25, 2016 Category: Molecular Biology Authors: Yu, G., Yang, N., Li, F., Chen, M., Guo, C. J., Wang, C., Hu, D., Yang, Y., Zhu, C., Wang, Z., Shi, H., Gegen, T., Tang, M., He, Q., Liu, Q., Tang, Z. Tags: Research Article Source Type: research

Impacts of anti-nerve growth factor antibody on pain-related behaviors and expressions of opioid receptor in spinal dorsal horn and dorsal root ganglia of rats with cancer-induced bone pain
Conclusions Anti-nerve growth factor could reduce hyperalgesia in the cancer-induced bone pain rats, and the antinociceptive effects were related with the upregulation of μ-opioid receptor. (Source: Molecular Pain)
Source: Molecular Pain - April 25, 2016 Category: Molecular Biology Authors: Yao, P., Ding, Y., Wang, Z., Ma, J., Hong, T., Zhu, Y., Li, H., Pan, S. Tags: Research Article Source Type: research

ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue
Conclusions These findings suggest that the pERK-pGluR1 cascade is involved in central sensitization of trigeminal spinal subnucleus caudalis nociceptive neurons, thus resulting in tongue mechanical hyperalgesia associated with tongue drying. (Source: Molecular Pain)
Source: Molecular Pain - April 25, 2016 Category: Molecular Biology Authors: Nakaya, Y., Tsuboi, Y., Okada-Ogawa, A., Shinoda, M., Kubo, A., Chen, J. Y., Noma, N., Batbold, D., Imamura, Y., Sessle, B. J., Iwata, K. Tags: Research Article Source Type: research