[EXPRESS] Electrophysiological property and chemical sensitivity of primary afferent neurons that innervate rat whisker hair follicles
(Source: Molecular Pain)
Source: Molecular Pain - December 6, 2016 Category: Molecular Biology Authors: Ikeda, R., Gu, J. Tags: Articles Source Type: research
G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury
Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of dorsal root ganglia. G9a is a repressor of gene expression. We found that nerve injury-induced increases in G9a and its catalyzed repressive marker H3K9m2 are responsible for epigenetic silencing of Oprm1, Oprk1, and Oprd1 genes in the injured dorsal root ganglia. Blocking...
Source: Molecular Pain - December 6, 2016 Category: Molecular Biology Authors: Liang, L., Zhao, J.-Y., Gu, X., Wu, S., Mo, K., Xiong, M., Marie Lutz, B., Bekker, A., Tao, Y.-X. Tags: Research Article Source Type: research
Exploring novel paths towards protein signatures of chronic pain
Pain is a major symptom of many medical conditions and the worldwide number one reason for people to seek medical assistance. It affects the quality of life of patients and poses a heavy financial burden on society with high costs of treatment and lost productivity. Furthermore, the treatment of chronic pain presents a big challenge as pain therapeutics often lack efficacy and exhibit minimal safety profiles. The latter can be largely attributed to the fact that current therapies target molecules with key physiological functions throughout the body. In light of these difficulties, the identification of proteins specificall...
Source: Molecular Pain - December 4, 2016 Category: Molecular Biology Authors: Gomez-Varela, D., Schmidt, M. Tags: Commentary Source Type: research
Involvement of mesolimbic dopaminergic network in neuropathic pain relief by treadmill exercise: A study for specific neural control with Gi-DREADD in mice
Conclusion
Our findings suggest that the dopaminergic pathway from the ventral tegmental area to the nucleus accumbens is involved in the anti-nociception under low-intensity exercise under a neuropathic pain-like state. (Source: Molecular Pain)
Source: Molecular Pain - November 30, 2016 Category: Molecular Biology Authors: Wakaizumi, K., Kondo, T., Hamada, Y., Narita, M., Kawabe, R., Narita, H., Watanabe, M., Kato, S., Senba, E., Kobayashi, K., Kuzumaki, N., Yamanaka, A., Morisaki, H., Narita, M. Tags: Research Article Source Type: research
Selective antagonism of TRPA1 produces limited efficacy in models of inflammatory- and neuropathic-induced mechanical hypersensitivity in rats
The transient receptor potential ankyrin 1 (TRPA1) channel has been implicated in pathophysiological processes that include asthma, cough, and inflammatory pain. Agonists of TRPA1 such as mustard oil and its key component allyl isothiocyanate (AITC) cause pain and neurogenic inflammation in humans and rodents, and TRPA1 antagonists have been reported to be effective in rodent models of pain. In our pursuit of TRPA1 antagonists as potential therapeutics, we generated AMG0902, a potent (IC90 of 300 nM against rat TRPA1), selective, brain penetrant (brain to plasma ratio of 0.2), and orally bioavailable small molecule TRPA1 a...
Source: Molecular Pain - November 28, 2016 Category: Molecular Biology Authors: Lehto, S. G., Weyer, A. D., Youngblood, B. D., Zhang, M., Yin, R., Wang, W., Teffera, Y., Cooke, M., Stucky, C. L., Schenkel, L., Geuns-Meyer, S., Moyer, B. D., Wild, K. D., Gavva, N. R. Tags: Research Article Source Type: research
Consistent sex-dependent effects of PKM{zeta} gene ablation and pharmacological inhibition on the maintenance of referred pain
Conclusion
We show pharmacological inhibition and genetic ablation of PKM consistently attenuate long-lasting pain hypersensitivity. However, differential effects in models of referred versus inflammatory and neuropathic pain, and in males versus females, highlight the roles of afferent input-dependent masking and sex differences in the maintenance of pain hypersensitivity. (Source: Molecular Pain)
Source: Molecular Pain - November 28, 2016 Category: Molecular Biology Authors: Nasir, H., Mahboubi, H., Gyawali, S., Ding, S., Mickeviciute, A., Ragavendran, J. V., Laferriere, A., Stochaj, U., Coderre, T. J. Tags: Research Article Source Type: research
Hippocampal activation of microglia may underlie the shared neurobiology of comorbid posttraumatic stress disorder and chronic pain
The high comorbidity rates of posttraumatic stress disorder and chronic pain have been widely reported, but the underlying mechanisms remain unclear. Emerging evidence suggested that an excess of inflammatory immune activities in the hippocampus involved in the progression of both posttraumatic stress disorder and chronic pain. Considering that microglia are substrates underlying the initiation and propagation of the neuroimmune response, we hypothesized that stress-induced activation of hippocampal microglia may contribute to the pathogenesis of posttraumatic stress disorder-pain comorbidity. We showed that rats exposed t...
Source: Molecular Pain - November 14, 2016 Category: Molecular Biology Authors: Sun, R., Zhang, Z., Lei, Y., Liu, Y., Lu, C., Rong, H., Sun, Y., Zhang, W., Ma, Z., Gu, X. Tags: Research Article Source Type: research
A randomized placebo-controlled pilot study of the efficacy and safety of D-cycloserine in people with chronic back pain
Conclusion
The difference in mean pain between the D-cycloserine and placebo groups did not reach statistical significance. However, a clinically meaningful effect size in the magnitude of pain relief was observed with a consistent pattern across multiple outcome measures with good safety, supporting further research into the effectiveness of D-cycloserine for chronic back pain. (Source: Molecular Pain)
Source: Molecular Pain - November 14, 2016 Category: Molecular Biology Authors: Schnitzer, T. J., Torbey, S., Herrmann, K., Kaushal, G., Yeasted, R., Vania Apkarian, A. Tags: Research Article Source Type: research
Spinal astrocytic activation contributes to mechanical allodynia in a rat model of cyclophosphamide-induced cystitis
Conclusions
Our results demonstrated that astrocytic activation but not microglial activation contributed to the allodynia in cyclophosphamide-induced cystitis and IL-1β released from astrocytes might bind to its endogenous receptor on the neurons inducing the phosphorylation of NR1 subunit, leading to sensory neuronal hyperexcitability and pathological pain. (Source: Molecular Pain)
Source: Molecular Pain - November 14, 2016 Category: Molecular Biology Authors: Liu, B., Su, M., Tang, S., Zhou, X., Zhan, H., Yang, F., Li, W., Li, T., Xie, J. Tags: Research Article Source Type: research
Preventing painful age-related bone fractures: Anti-sclerostin therapy builds cortical bone and increases the proliferation of osteogenic cells in the periosteum of the geriatric mouse femur
Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient’s functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring. A major question, however, is whether an osteo-anabolic agent can stimulate the pr...
Source: Molecular Pain - November 10, 2016 Category: Molecular Biology Authors: Thompson, M. L., Chartier, S. R., Mitchell, S. A., Mantyh, P. W. Tags: Research Article Source Type: research
Differential contributions of vasopressin V1A and oxytocin receptors in the amygdala to pain-related behaviors in rats
Neuroplastic changes in the amygdala account for emotional-affective aspects of pain and involve neuropeptides such as calcitonin gene-related peptide and corticotropin-releasing factor. Another neuropeptide system, central arginine vasopressin, has been implicated in neuropsychiatric disorders, but its role in pain-related emotional expression and neuroplasticity remains to be determined. Here, we tested the hypothesis that arginine vasopressin in the amygdala contributes to pain-related emotional-affective responses, using stereotaxic applications of arginine vasopressin and antagonists for G-protein coupled vasopressin ...
Source: Molecular Pain - November 10, 2016 Category: Molecular Biology Authors: Cragg, B., Ji, G., Neugebauer, V. Tags: Short Report Source Type: research
A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels
Small fiber neuropathy is a painful sensory nervous system disorder characterized by damage to unmyelinated C- and thinly myelinated A- nerve fibers, clinically manifested by burning pain in the distal extremities and dysautonomia. The clinical onset in adulthood suggests a time-dependent process. The mechanisms that underlie nerve fiber injury in small fiber neuropathy are incompletely understood, although roles for energetic stress have been suggested. In the present study, we report time-dependent degeneration of neurites from dorsal root ganglia neurons in culture expressing small fiber neuropathy-associated G856D muta...
Source: Molecular Pain - November 6, 2016 Category: Molecular Biology Authors: Rolyan, H., Liu, S., Hoeijmakers, J. G., Faber, C. G., Merkies, I. S., Lauria, G., Black, J. A., Waxman, S. G. Tags: Research Article Source Type: research
Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis
Conclusions
The data for the first time revealed specific signaling pathways leading to cyclophosphamide-induced bladder hyperactivity and pain, including the activation of mTOR and PI3K. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis. (Source: Molecular Pain)
Source: Molecular Pain - October 24, 2016 Category: Molecular Biology Authors: Liang, S., Li, J., Gou, X., Chen, D. Tags: Research Article Source Type: research
MicroRNA-30b regulates expression of the sodium channel Nav1.7 in nerve injury-induced neuropathic pain in the rat
Voltage-gated sodium channels, which are involved in pain pathways, have emerged as major targets for therapeutic intervention in pain disorders. Nav1.7, the tetrodotoxin-sensitive voltage-gated sodium channel isoform encoded by SCN9A and predominantly expressed in pain-sensing neurons in the dorsal root ganglion, plays a crucial role in nociception. MicroRNAs are highly conserved, small non-coding RNAs. Through binding to the 3' untranslated region of their target mRNAs, microRNAs induce the cleavage and/or inhibition of protein translation. Based on bioinformatics analysis using TargetScan software, we determined that mi...
Source: Molecular Pain - October 18, 2016 Category: Molecular Biology Authors: Shao, J., Cao, J., Wang, J., Ren, X., Su, S., Li, M., Li, Z., Zhao, Q., Zang, W. Tags: Research Article Source Type: research
Transcriptome analysis of trigeminal ganglia following masseter muscle inflammation in rats
Conclusion
These findings should further advance our understanding of peripheral mechanisms involved in persistent craniofacial muscle pain conditions and provide a rational basis for identifying novel genes or sets of genes that can be potentially targeted for treating such conditions. (Source: Molecular Pain)
Source: Molecular Pain - October 3, 2016 Category: Molecular Biology Authors: Chung, M.-K., Park, J., Asgar, J., Ro, J. Y. Tags: Research Article Source Type: research
