HDAC and HAT inhibitors differently affect analgesia mediated by group II metabotropic glutamate receptors
Conclusions: Our results demonstrate that systemically injected CUR is able to inhibit H3 and H4 acetylation in the DRG and to down-regulate mGlu2 receptors in the spinal cord. We also demonstrate that long term modification of the mGlu2 expression affects the analgesic properties of the orthosteric mGlu2/3 agonist, LY379268. These data open up the possibility that epigenetic modulators might be given in combination with "traditional" drugs in a context of a multi target approach for a better analgesic efficacy. (Source: Molecular Pain)
Source: Molecular Pain - November 18, 2014 Category: Molecular Biology Authors: Magda ZammataroMaria Angela SortinoCarmela ParentiRobert GereauSantina Chiechio Source Type: research

Cannabinoid receptor 2 agonist attenuates pain related behavior in rats with chronic alcohol/high fat diet induced pancreatitis
Conclusion: LY3038404 HCl, a potent CB2 receptor agonist, possesses tissue protective and analgesic properties without effects on higher brain function. Thus, activation of CB2 receptors is suggested as a potential therapeutic target for visceral inflammation and pain management. (Source: Molecular Pain)
Source: Molecular Pain - November 17, 2014 Category: Molecular Biology Authors: Liping ZhangRobert KlineTerry McNearneyMichael JohnsonKarin Westlund Source Type: research

TRPV1 antagonist attenuates postoperative hypersensitivity by central and peripheral mechanisms
Conclusions: Our experiments suggest that both peripheral and spinal cord TRPV1 receptors are involved in increased cutaneous sensitivity following surgical incision. The analgesic effect of the TRPV1 receptor antagonist was especially evident in the reduction of thermal hyperalgesia. The activation of TRPV1 receptors represents an important mechanism in the development of postoperative hypersensitivity. (Source: Molecular Pain)
Source: Molecular Pain - November 17, 2014 Category: Molecular Biology Authors: Eva UchytilovaDiana SpicarovaJiri Palecek Source Type: research

Adenylyl cyclase subtype 1 is essential for late-phase long term potentiation and spatial propagation of synaptic responses in the anterior cingulate cortex of adult mice
Long-term potentiation (LTP) is a key cellular mechanism for pathological pain in the central nervous system. LTP contains at least two different phases: early-phase LTP (E-LTP) and late-phase LTP (L-LTP). Among several major cortical areas, the anterior cingulate cortex (ACC) is a critical brain region for pain perception and its related emotional changes. Periphery tissue or nerve injuries cause LTP of excitatory synaptic transmission in the ACC. Our previous studies have demonstrated that genetic deletion of calcium-stimulated adenylyl cyclase 1 (AC1) or pharmacological application of a selective AC1 inhibitor NB001 blo...
Source: Molecular Pain - October 10, 2014 Category: Molecular Biology Authors: Tao ChenGerile O¿DenQian SongKohei KogaMing-Ming ZhangMin Zhuo Source Type: research

¿9-nicotinic acetylcholine receptors contribute to the maintenance of chronic mechanical hyperalgesia, but not thermal or mechanical allodynia
Conclusions: The alpha9-nAChR is not involved in acute pain perception or chronic thermal or mechanical allodynia but does contribute to the intensity and duration of chronic mechanical hyperalgesia, suggesting that pain-relieving actions of antagonists that target this site may be restricted to high threshold mechanosensation. The alpha9-nAChR appears to be a valid target for pharmacological compounds that alleviate long-term mechanical hyperalgesia and may be of use as a prophylactic drug to prevent the development of some symptoms of chronic pain. (Source: Molecular Pain)
Source: Molecular Pain - October 2, 2014 Category: Molecular Biology Authors: Sarasa MohammadiMacdonald Christie Source Type: research

Gabapentin reverses central hypersensitivity and suppresses medial prefrontal cortical glucose metabolism in rats with neuropathic pain
Conclusions: Our results indicate that GBP analgesic effect may be mediated by reversing central hypersensitivity, and suppressing mPFC, a crucial part of the cortical representation of pain, in the brain. (Source: Molecular Pain)
Source: Molecular Pain - September 25, 2014 Category: Molecular Biology Authors: Hsiao-Chun LinYu-Hsin HuangTzu-Hao ChaoWen-Ying LinWei-Zen SunChen-Tung Yen Source Type: research

Sustained pain-related depression of behavior: effects of intraplantar formalin and complete freund¿s adjuvant on intracranial self-stimulation (ICSS) and endogenous kappa opioid biomarkers in rats
Conclusions: These results suggest differential efficacy of sustained pain stimuli to depress brain reward function in rats as assessed with ICSS. Formalin-induced depression of ICSS does not appear to engage brain kappa opioid systems. (Source: Molecular Pain)
Source: Molecular Pain - September 23, 2014 Category: Molecular Biology Authors: Michael LeitlDavid PotterKejun ChengKenner RiceWilliam CarlezonS Negus Source Type: research

Sustained pain-related depression of behavior: effects of intraplantar formalin and complete freund's adjuvant on intracranial self-stimulation (ICSS) and endogenous kappa opioid biomarkers in rats
Conclusions: These results suggest differential efficacy of sustained pain stimuli to depress brain reward function in rats as assessed with ICSS. Formalin-induced depression of ICSS does not appear to engage brain kappa opioid systems. (Source: Molecular Pain)
Source: Molecular Pain - September 23, 2014 Category: Molecular Biology Authors: Michael LeitlDavid PotterKejun ChengKenner RiceWilliam CarlezonS Negus Source Type: research

Transient receptor potential ankyrin 1 in spinal cord dorsal horn is involved in neuropathic pain in nerve root constriction rats
Conclusion: These data showed that the TRPA1 antagonist had an inhibitory effect on mechanical hypersensitivity and hyperalgesia as well as on physiological pain transmission in the spinal cord dorsal horn. This suggests that TRPA1 is consistently involved in excitatory synaptic transmission even in the physiological state and has a role in coordinating pain transmission. (Source: Molecular Pain)
Source: Molecular Pain - September 6, 2014 Category: Molecular Biology Authors: Tsuyoshi MiyakawaYoshinori TerashimaTsuneo TakebayashiKatsumasa TanimotoTakehito IwaseIzaya OgonTakeshi KobayashiNoritsugu TohseToshihiko Yamashita Source Type: research

Validation of four reference genes for quantitative mRNA expression studies in a rat model of inflammatory injury
Conclusions: This study validated the four genes Hprt1, Actb, Mapk6 or B2m and showed that any one or combination of two of them are good reference genes for normalization of mRNA expression in qPCR experiments in the spinal cord and RVM in the CFA model of inflammatory injury. (Source: Molecular Pain)
Source: Molecular Pain - September 4, 2014 Category: Molecular Biology Authors: Roxanne WalderAnne-Sophie WattiezStephanie WhiteBlanca Marquez de PradoMarta HamityDonna Hammond Source Type: research

Optimization of a cisplatin model of chemotherapy-induced peripheral neuropathy in mice: use of vitamin C and sodium bicarbonate pretreatments to reduce nephrotoxicity and improve animal health status
Conclusions: Studies employing cisplatin should include NaHCO3 or vitamin C pretreatment to improve animal health status and reduce nephrotoxicity (lower creatinine and kidney weight ratio) without affecting the development of chemotherapy-induced neuropathy or analgesic efficacy. (Source: Molecular Pain)
Source: Molecular Pain - September 4, 2014 Category: Molecular Biology Authors: Josée GuindonLiting DengBaochang FanJim Wager-MillerAndrea Hohmann Source Type: research

Spatial and temporal pattern of changes in the number of GAD65-immunoreactive inhibitory terminals in the rat superficial dorsal horn following peripheral nerve injury
Inhibitory interneurons are an important component of dorsal horn circuitry where they serve to modulate spinal nociception. There is now considerable evidence indicating that reduced inhibition in the spinal dorsal horn contributes to neuropathic pain. A loss of these inhibitory neurons after nerve injury is one of the mechanisms being proposed to account for reduced inhibition; however, this remains controversial. This is in part because previous studies have focused on global measurements of inhibitory neurons without assessing the number of inhibitory synapses. To address this, we conducted a quantitative analysis of t...
Source: Molecular Pain - September 4, 2014 Category: Molecular Biology Authors: Louis-Etienne LorenzoClaire MagnussenAndrea BaileyManon LouisYves De KoninckAlfredo Ribeiro-da-Silva Source Type: research

Preclinical toxicity evaluation of AAV for pain: evidence from human AAV studies and from the pharmacology of analgesic drugs
Gene therapy with adeno-associated virus (AAV) has been advanced in the last few years from promising results in animal models to >100 clinical trials (reported or under way). While vector availability was a substantial hurdle a decade ago, innovative new production methods now routinely match the scale of AAV doses required for clinical testing. These advances may become relevant to translational research in the chronic pain field. AAV for pain targeting the peripheral nervous system was proven to be efficacious in rodent models several years ago, but has not yet been tested in humans. The present review addresses the ste...
Source: Molecular Pain - September 2, 2014 Category: Molecular Biology Authors: Josef PletichaLukas HeilmannChristopher EvansAravind AsokanRichard SamulskiAndreas Beutler Source Type: research

Involvement of the chemokine CCL3 and the purinoceptor P2X7 in the spinal cord in paclitaxel-induced mechanical allodynia
Conclusions: Our findings suggest a contribution of CCL3 and P2X7Rs in the SDH to paclitaxel-induced allodynia and may provide new therapeutic targets for paclitaxel-induced painful neuropathy. (Source: Molecular Pain)
Source: Molecular Pain - August 15, 2014 Category: Molecular Biology Authors: Ryutaro Ochi-ishiKenichiro NagataTomoyuki InoueHidetoshi Tozaki-SaitohMakoto TsudaKazuhide Inoue Source Type: research

Cyclic phosphatidic acid relieves osteoarthritis symptoms
Conclusions: Our results suggest that 2ccPA significantly reduces the pain response to OA by inducing hyaluronic acid production and suppressing MMP-1, -3, and -13 production in synoviocytes and chondrocytes. (Source: Molecular Pain)
Source: Molecular Pain - August 14, 2014 Category: Molecular Biology Authors: Mari GotohAya NaganoRyoko TsukaharaHiromu MurofushiToshiro MorohoshiKazuyuki OtsukaKimiko Murakami-Murofushi Source Type: research