Articles: neuropathic-pain.
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Bioorg. Med. Chem. Lett. · Jul 2014
DDD-028: a potent potential non-opioid, non-cannabinoid analgesic for neuropathic and inflammatory pain.
DDD-028 (4), a novel pentacyclic pyridoindolobenzazepine derivative was evaluated in vitro for receptor binding affinity and in vivo for analgesic activity using rodent models of neuropathic and inflammatory pain. DDD-028 does not bind to opioid, cannabinoid, dopamine, or histamine receptors. ⋯ Visual observation of all the animals used in these studies indicated that DDD-028 is well tolerated without any sedation. Thus, DDD-028 seems to be a promising candidate for the treatment of neuropathic and inflammatory pain without the possible side effects or abuse potential associated with opioid or cannabinoid activities.
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Electroacupuncture has traditionally been used to treat pain, but its effect on pain following brachial plexus injury is still unknown. In this study, rat models of an avulsion injury to the left brachial plexus root (associated with upper-limb chronic neuropathic pain) were given electroacupuncture stimulation at bilateral Quchi (LI11), Hegu (LI04), Zusanli (ST36) and Yanglingquan (GB34). ⋯ Immunofluorescence staining showed that the expression of β-endorphins in the arcuate nucleus was significantly increased after therapy. Thus, experimental findings indicate that electroacupuncture can attenuate neuropathic pain after brachial plexus injury through upregulating β-endorphin expression.
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Comparative Study
Face-to-face comparison of the predictive validity of two models of neuropathic pain in the rat: analgesic activity of pregabalin, tramadol and duloxetine.
We compared the preclinical analgesic activity of three marketed drugs with different pharmacological properties, pregabalin, tramadol and duloxetine, described as effective against neuropathic pain in the clinic. These drugs were tested against evoked pain in two different neuropathic models in the rat, the Bennett (CCI) and the Chung (SNL) models. The selected endpoints were tactile allodynia, tactile hyperalgesia, heat hyperalgesia and cold allodynia. ⋯ It also displayed efficacy against tactile hyperalgesia in the CCI model and against cold allodynia in the Chung model. These data confirm that the CCI and the Chung models of neuropathic pain do not detect the activity of analgesics with the same sensitivity. Furthermore, the mode of stimulation (tactile or thermal) and the type of endpoint (allodynia or hyperalgesia) can further influence the observed efficacy of gold standards as well as novel compounds developed for treating neuropathic pain symptoms.
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Biochem. Biophys. Res. Commun. · Jul 2014
Upregulation of tumor necrosis factor-alpha in nucleus accumbens attenuates morphine-induced rewarding in a neuropathic pain model.
Treatment of neuropathic pain with opioid analgesics remains controversial and a major concern is the risk of addiction. Here, we investigated this issue with spared nerve injury (SNI) model of neuropathic pain in rats and mice. SNI prevented conditioned place preference (CPP) induced by low dose (3.5mg/kg) of morphine (MOR), which was effective for anti-allodynia, but not by high dose (⩾5.0 mg/kg) of MOR. ⋯ Accordingly, the increase in DA reuptake but not decrease in its synthesis may lead to the reduction of DA level. Finally, the upregulation of DAT in the NAcc of SNI animals was again blocked by either genetic deletion of TNFR1 or NAcc injection of anti-TNF-α, and was mimicked by NAcc injection of TNF-α in sham animals. Thus, our data provided novel evidence that upregulation of TNF-α in NAcc may attenuate MOR-induced rewarding by upregulation of DAT in NAcc under neuropathic pain condition.
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Ketamine, in subanesthetic doses, produces systemic analgesia in chronic pain settings, an action largely attributed to block of N-methyl-D-aspartate receptors in the spinal cord and inhibition of central sensitization processes. N-methyl-D-aspartate receptors also are located peripherally on sensory afferent nerve endings, and this provided the initial impetus for exploring peripheral applications of ketamine. Ketamine also produces several other pharmacological actions (block of ion channels and receptors, modulation of transporters, anti-inflammatory effects), and while these may require higher concentrations, after topical (e.g., as gels, creams) and peripheral application (e.g., localized injections), local tissue concentrations are higher than those after systemic administration and can engage lower affinity mechanisms. ⋯ In controlled trials of neuropathic pain with topical ketamine combinations, there were improvements in some outcomes, but optimal dosing and drug combinations were not clear. Given orally (as a gargle, throat swab, localized peritonsillar injections), ketamine produced significant oral/throat analgesia in controlled trials in postoperative settings. Topical analgesics are likely more effective in particular conditions (patient factors, disease factors), and future trials of topical ketamine should include a consideration of factors that could predispose to favorable outcomes.