Articles: neuropathic-pain.
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VGF (nonacronymic) is a granin-like protein that is packaged and proteolytically processed within the regulated secretory pathway. VGF and peptides derived from its processing have been implicated in neuroplasticity associated with learning, memory, depression, and chronic pain. In sensory neurons, VGF is rapidly increased following peripheral nerve injury and inflammation. ⋯ In mice injected intradermally with complete Freund adjuvant, intrathecal treatment with anti-TLQP-21 immediately prior to or 5hours after induction of inflammation dose-dependently inhibited tactile hypersensitivity and thermal hyperalgesia. Intrathecal anti-TL21 administration also attenuated the development and maintenance of tactile hypersensitivity in the spared nerve injury model of neuropathic pain. These results provide evidence that endogenous TLQP-21 peptide contributes to the mechanisms of spinal neuroplasticity after inflammation and nerve injury.
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Peripheral nerve injury can result in the formation of neuroma/nerve entrapment, a persistent peripheral neuropathic pain state which is often refractory to invasive interventions or medications. Therefore, there is a need in the field of pain management to develop innovative noninvasive therapy in treating post-traumatic peripheral neuropathic pain states. A new intervention, transcutaneous magnetic stimulation (tMS), is derived from the use of transcranial magnetic stimulation in which a rapid discharge of electric current is converted into dynamic magnetic flux for modulating neuronal functions. ⋯ tMS offers a noninvasive treatment option for neuroma-related neuropathic pain conditions. Randomized controlled studies are required in further validating the efficacy of this treatment modality. Additional studies are also needed to assess the underlying electrophysiological mechanisms of the observed analgesic benefit.
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Annals of neurosciences · Jul 2014
Pathogenesis of spinal cord injury induced edema and neuropathic pain: expression of multiple isoforms of wnk1.
Neuropathic pain (NP) is a common occurrence following spinal cord injury (SCI). Identification of specific molecular pathways that are involved in pain syndromes has become a major priority in current SCI research. We have investigated the role of a cation-dependent chloride transporter, Cl-regulatory protein Na(+)-K(+)-Cl(-) 1 (NKCC1), phosphorylation profile of NKCC1 and its specific involvement in neuropathic pain following contusion SCI (cSCI) using a rat model. Administration of the NKCC1 inhibitor bumetanide (BU) increases the mean hindpaw withdrawal latency time (WLT), thermal hyperalgesia (TH) following cSCI. These results demonstrate implication of NKCC1 co-transporter and BUin SCI-induced neuropathic pain. The with-no-lysine (K)-1 (WNK1) kinase has been shown to be an important regulator of NKCC1 phosphorylation in many systems, including nocioception. Mutations in a neuronal-specific exon of WNK1 (HSN2) was identified in patients that have hereditary sensory neuropathy type II (HSANII) also implicates WNK1 in nocioception, such that these patients have loss of perception to pain, touch and heat. In our ongoing research we proposed two studies utilizing our contusion SCI (cSCI) NP model of rat. ⋯ This data implicates the NKCC1/WNK1/WNK1HSN2 involvement in post-injury response that contributes to the development of neuropathic pain. Targeting this system may have therapeutic benefit.
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Anesthesia and analgesia · Jul 2014
Phα1β, a Peptide from the Venom of the Spider Phoneutria nigriventer Shows Antinociceptive Effects after Continuous Infusion in a Neuropathic Pain Model in Rats.
Neuropathic pain is a severe painful pathology that is difficult to treat. One option for its management is the continuous intrathecal (i.t.) infusion of ziconotide (the Conus magnus peptide ω-conotoxin MVIIA), which, in addition to being effective, produces serious adverse effects at analgesic doses. Single i.t. administration of Phα1β, a peptide purified from the venom of the spider Phoneutria nigriventer, has antinociceptive effects with a greater therapeutic window than ziconotide in rodents. To further evaluate its analgesic potential, we investigated the antinociceptive and toxic effects of Phα1β after single or continuous i.t. infusion in a rat model of neuropathic pain. ⋯ Thus, we have shown for the first time that the continuous i.t. delivery of Phα1β produces analgesia disconnected from toxicity in a relevant model of neuropathic pain, indicating that it is an effective and safe drug with a great potential to treat pain.
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Anesthesia and analgesia · Jul 2014
The Effect of Intrathecal Administration TRPA1 Antagonists in a Rat Model of Neuropathic Pain.
The fact that transient receptor potential ankyrin 1 (TRPA1) on the peripheral terminals could attenuate hyperalgesia is widely accepted, but the effect of spinal TRPA1 in the modulation of hyperalgesia has not been fully demonstrated. In the present study, we investigated the effect of intrathecal (i.t.) administration TRPA1 antagonists on chronic pain and expression of TRPA1 and phosphorylation N-methyl-D-aspartate receptor 2B subunit (p-NR2B) in the spinal cord with chronic compression of the dorsal root ganglia (CCD) in rats. ⋯ These data demonstrated that the i.t. administration of TRPA1 antagonists could attenuate neuropathic pain in CCD rats, and this effect could be partially reduced by p-NR2B receptor expression in spinal cord.