Articles: neuralgia.
-
Lamiophlomis rotata (L. rotata, Duyiwei) is an orally available Tibetan analgesic herb widely prescribed in China. Shanzhiside methylester (SM) is a principle effective iridoid glycoside of L. rotata and serves as a small molecule glucagon-like peptide-1 (GLP-1) receptor agonist. This study aims to evaluate the signal mechanisms underlying SM anti-allodynia, determine the ability of SM to induce anti-allodynic tolerance, and illustrate the interactions between SM and morphine, or SM and β-endorphin, in anti-allodynia and anti-allodynic tolerance. ⋯ SM and exenatide specifically activated spinal p38 MAPK phosphorylation. These results indicate that SM reduces neuropathic pain by activating spinal GLP-1 receptors and subsequently stimulating microglial β-endorphin expression via the p38 MAPK signaling. Stimulation of the endogenous β-endorphin expression may be a novel and effective strategy for the discovery and development of analgesics for the long-term treatment of chronic pain.
-
Phosphodiesterase 4 (PDE4) is an adenosine cyclic 3,5-monophosphate-specific degradative enzyme, which is closely associated with the inflammatory response. Among its four subtypes (A-D), it remains unclear which one exerts suppressive effects on inflammation and reduces neuropathic pain. The present study aimed to examine the modulation of neuroinflammation by PDE4 subtypes in the spinal cord of a rat model of L5 spinal nerve ligation (SNL)-induced neuropathic pain. ⋯ Subtype-specific siRNA significantly suppressed the elevated expression levels; however, only rats treated with PDE4B siRNA exhibited improved MWT and TWL. Further analysis of the PDE4B siRNA-treated rats demonstrated that 8 days after SNL, the intensity of p-ERK was reduced, the expression levels of CD11b and glial fibrillary acidic protein GFAP were reduced, as well as the expression levels of proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β and IL-6. These results suggested that selective inhibition of PDE4B may relieve neuropathic pain, potentially via the suppression of glial activation and the release of cytokines in the spinal cord.
-
Journal of anesthesia · Feb 2016
The possible involvement of JNK activation in the spinal dorsal horn in bortezomib-induced allodynia: the role of TNF-α and IL-1β.
Bortezomib (BTZ), a widely used chemotherapeutic drug, is closely associated with the development of painful peripheral neuropathy, but the mechanism underlying the induction of this disorder by BTZ remains largely unclear. To examine this association, we have evaluated the activation of mitogen-activated protein kinase (MAPK) family members in the spinal dorsal horn and the role of tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) in BTZ-induced allodynia in rats. ⋯ Our results suggest that the TNF-α or IL-1β/JNK pathway in the spinal dorsal horn may play a critical role in the development of painful peripheral neuropathy induced by BTZ.
-
A workshop of the 2015 International Neuropathic Pain Congress was focused on potassium channels to propose emerging ideas on the role of these channels on pain modulation and to determine whether they can become relevant targets for designing novel analgesic compounds. Two kinds of potassium channels were particularly evoked: selected subunits of the voltage-gated potassium (Kv) and of the K2P channel families. ⋯ Throughout this review, the role of potassium channels in pain is obvious, which renders them potential targets for innovative analgesics with peripheral and/or central action depending on the channel. Clearly, some preliminary results obtained with known or novel potassium channel openers suggest that they might represent a novel class of analgesics in neuropathic pain or other pathological contexts.
-
The treatment of pain is a complex process that requires a team approach. This article provides an overview of the pharmaceutical treatments available. ⋯ Pharmaceuticals are an important component in the treatment of chronic pain and opioids are often not a good solution. Knowing what other medications are available can improve the care for these challenging patients.