Articles: hyperalgesia.
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Neuromolecular medicine · Mar 2013
Comparative StudyActivation of tetrodotoxin-resistant sodium channel NaV1.9 in rat primary sensory neurons contributes to melittin-induced pain behavior.
Tetrodotoxin-resistant (TTX-R) sodium channels NaV1.8 and NaV1.9 in dorsal root ganglion (DRG) neurons play important roles in pathological pain. We recently reported that melittin, the major toxin of whole bee venom, induced action potential firings in DRG neurons even in the presence of a high concentration (500 nM) of TTX, indicating the contribution of TTX-R sodium channels. This hypothesis is fully investigated in the present study. ⋯ Neither NaV1.8 AS ODN nor NaV1.9 AS ODN affects melittin-induced mechanical hypersensitivity. These results provide previously unknown evidence that upregulation of NaV1.9, but not NaV1.8, in small-sized DRG neurons contributes to melittin-induced heat hypersensitivity. Furthermore, melittin-induced biological effect indicates a potential strategy to study properties of TTX-R sodium channels.
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Yonsei medical journal · Mar 2013
Intrathecal lamotrigine attenuates mechanical allodynia and suppresses microglial and astrocytic activation in a rat model of spinal nerve ligation.
Lamotrigine, a novel anticonvulsant, is a sodium channel blocker that is efficacious in certain forms of neuropathic pain. Recently, microglial and astrocytic activation has been implicated in the development of nerve injury-induced neuropathic pain. We have assessed the effects of continuous intrathecal administration of lamotrigine on the development of neuropathic pain and glial activation induced by L5/6 spinal-nerve ligation in rats. ⋯ Continuously administered intrathecal lamotrigine blocked the development of mechanical allodynia induced by SNL with suppression of microglial and astrocytic activation. Continuous intrathecal administration of lamotrigine may be a promising therapeutic intervention to prevent neuropathy.
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Reg Anesth Pain Med · Mar 2013
Effects of chronic administration of amitriptyline, gabapentin and minocycline on spinal brain-derived neurotrophic factor expression and neuropathic pain behavior in a rat chronic constriction injury model.
In animal models of neuropathic pain (NP), promising results have been reported with the administration of minocycline, possibly through inhibition of spinal brain-derived neurotrophic factor (BDNF) expression. No data are available on the effect of amitriptyline and gabapentin on spinal BDNF expression. If the mechanism of action of the latter drugs does not involve brain-derived NP inhibition, further clinical research in BDNF is warranted. ⋯ Minocycline and amitriptyline both reduce NP behavior in a sciatic CCI rat model, but only minocycline reduces spinal BDNF, indicating different modes of action of these 2 drugs. The observed actions of minocycline closely fit the clinical needs for the treatment of NP.
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Pharmacol. Biochem. Behav. · Mar 2013
Dissociated modulation of conditioned place-preference and mechanical hypersensitivity by a TRPA1 channel antagonist in peripheral neuropathy.
Transient receptor potential ankyrin 1 (TRPA1) channel antagonists have suppressed mechanical hypersensitivity in peripheral neuropathy, while their effect on ongoing neuropathic pain is not yet known. Here, we assessed whether blocking the TRPA1 channel induces place-preference, an index for the relief of ongoing pain, in two experimental rat models of peripheral neuropathy. Diabetic neuropathy was induced by streptozotocin and spared nerve injury (SNI) model of neuropathy by ligation of two sciatic nerve branches. ⋯ In diabetic and SNI models of neuropathy, CHEM failed to induce CPP at a dose that significantly attenuated mechanical hypersensitivity, independent of the route of drug administration or number of successive conditioning sessions. Intrathecal clonidine (an α2-adrenoceptor agonist; 10μg), in contrast, induced CPP in SNI but not control animals. The results indicate that ongoing pain, as revealed by CPP, is less sensitive to treatment by the TRPA1 channel antagonist than mechanical hypersensitivity in peripheral neuropathy.
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Cell. Mol. Neurobiol. · Mar 2013
Activation of different signals identified with glia cells contribute to the progression of hyperalgesia.
Hyperalgesia results from a decreased pain threshold, often subsequent to peripheral tissue damage. Recent reports revealed several promising mechanisms of hyperalgesia, but many issues remain unclear. The glial activation accompanying inflammation of neurotransmission in the spinal cord might be related to the initiation and maintenance of hyperalgesia. ⋯ The present results revealed that microglial activation resulting from the release of the phosphatase p38-MAPK, the transcription factor NF-κB, and BDNF contributes to the early stage of inflammatory pain. Astrocyte activation accompanying JNK activation contributes to subsequent hyperalgesia. Activation of different signals identified with glia cells is thought to contribute to the progression of hyperalgesia, which represents an applicable finding for the treatment of hyperalgesia.