Neuroscience letters
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Neuroscience letters · Nov 2012
Neuropathic pain and reactive gliosis are reversed by dialdehydic compound in neuropathic pain rat models.
The role of the purinergic system in the modulation of pain mechanisms suggests that it might be promising target for treating neuropathic pain. In this study we evaluated the effects of two different dialdehydic compounds: a modified stable adenosine (2-[1-(6-amminopurin-9-il)-2-osso-etossi]prop-2-enale, named MED1101), and oxidized ATP (Ox-ATP), in two different neuropathic pain rat models: the sciatic spared nerve injury (SNI) and paclitaxel evoked painful peripheral neuropathy (pPPN). Neuropathic animals were divided in groups as follows: (a) treated with intraperitoneal (i.p.) MED1101 or Ox-ATP for 21 days; (b) receiving vehicle (VEH) and (c) control (CTR) rats. ⋯ We evaluated by immunocytochemistry the astrocytic (GFAP) and microglial (Iba1) response on lumbar spinal cord sections. In either experimental models and using either substances, treated animals showed reduced allodynia and thermal hyperalgesia paralleled by a significant reduction of glial reaction in the spinal cord. These data prompt to hypothesize a potential role of dialdehydes as analgesic agent in chronic neuropathic pain and a possible role as anti-gliotic molecules.
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Human chronic pain sufferers frequently report problems with attention and concentration that affect daily functioning and quality of life. Chronic pain is also commonly associated with anxiety and depression. It is currently not known if the pain causes these co-morbidities, or if they are pre-disposing risk factors for the development of chronic pain. ⋯ Male Long Evans rats subjected to nerve injury remained hypersensitive to sensory stimuli from the time of injury to the 6-month post-injury assessment. At 6 months they were impaired on a visual non-selective, non-sustained attention task and displayed anxiety-like behaviors in the elevated plus maze. These findings show that cognitive disturbances observed during acute pain persist for months in a rodent chronic pain model and suggest that cognitive alterations in chronic pain patients are at least partially caused by the chronic pain state.
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Neuroscience letters · Nov 2012
Melanocortin 4 receptor antagonists attenuates morphine antinociceptive tolerance, astroglial activation and cytokines expression in the spinal cord of rat.
Chronic use of morphine is accompanied by the development of morphine tolerance, which is one of the major problems associated with opiate treatment. Experimental evidence indicates that melanocortin 4 receptor (MC4R) is involved in development of morphine tolerance. Therefore, we investigated the influence of repeated intrathecal injection of a MC4R antagonist (HS014) on the development of morphine tolerance as measured by hot-plate test. ⋯ A single administration of an MC4R antagonist restored morphine analgesic potency in morphine tolerant rats. Using immunohistochemical staining, we demonstrated the administration of MC4R during the induction of morphine tolerance inhibited the activation of astrocytes; reduced the expression of proinflammatory cytokines interleukin-1β, IL-6, and tumor necrosis factor-α; upregulated the expression of anti-inflammatory cytokines IL-10 at the L5 lumbar spinal cord. These results suggest that MC4R may be involved in the mechanisms of morphine tolerance and antagonists of this receptor may be a possible new target in the search for strategies preventing the development of morphine tolerance.
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Neuroscience letters · Oct 2012
Dexmedetomidine decreases hyperalgesia in neuropathic pain by increasing acetylcholine in the spinal cord.
The activation of α2-adrenoceptors has attracted attention as a therapeutic target for neuropathic pain, which remains a clinical challenge. In the present study, we examined the interaction between α2-adrenergic and cholinergic signaling in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). Intrathecal administration of dexmedetomidine, which is a selective α2-adrenoceptor agonist (0.1-1.0 μg), dose-dependently suppressed hyperalgesia in SNL rats but did not alter paw withdrawal thresholds in normal rats. ⋯ The combination of an ineffective dose of intrathecal dexmedetomidine with intraperitoneal donepezil, which is a cholinesterase inhibitor, decreased neuropathic hypersensitivity. These results suggest that plasticity of the spinal noradrenergic-cholinergic axis only occurs in neuropathic pain states. Thus, drug combinations that strengthen the noradrenergic-cholinergic interaction may provide therapeutic benefit in neuropathic pain.
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Neuroscience letters · Oct 2012
Cell degeneration is not a primary causer for Connexin26 (GJB2) deficiency associated hearing loss.
Connexin26 (Cx26, GJB2) mutations can induce congenital deafness and are responsible for ∼50% of nonsyndromic hearing loss in children. Mouse models show that Cx26 deficiency induces cochlear development disorder, hair cell loss, and spiral ganglion (SG) neuron degeneration. Hair cell loss and cell degeneration have been considered as a primary causer responsible for Cx26 deficiency associated hearing loss. ⋯ Functional tests show that hair cells in Cx26 KO mice functioned normally; outer hair cells retained electromotility. These data suggest that cell degeneration is not a primary causer of Cx26 deficiency associated hearing loss. Some mechanisms other than cell degeneration, such as cochlear development disorders, may play an essential role in this common hereditary deafness.