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Constriction Injury (constriction + injury)
Kinds of Constriction Injury Selected AbstractsAltered Thyroid Hormones and Behavioural Change in a Sub-Population of Rats Following Chronic Constriction InjuryJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2010E. Kilburn-Watt Hypothyroidism is associated with a disturbance of behaviour and mood. There are also individuals, not classified as hypothyroid, with low to ,low normal' thyroid hormone levels and normal thyroid-stimulating hormone (TSH) levels who have mood and behavioural changes. As the peripheral thyroid hormones decrease, TSH is expected to increase. However, there are a number of physiological mechanisms known to suppress TSH. In the present study, we report on thyroid hormone regulation in a rat model of neuropathic pain and altered social behaviour that is usually transient, but is persistent in a sub-group of the population. Following ligation of the sciatic nerve, male Sprague-Dawley rats were assessed for social dominance towards an intruder: 20% showed persistently decreased social dominance. Plasma levels of thyroid hormones, TSH and corticosterone were measured before and on days 2, 3, 4, 5 and 6 after injury in 21 rats. The mean plasma thyroxine (T4), free thyroxine (fT4) and triiodothyronine (T3) levels decreased significantly post-injury in rats with persistently changed behaviour compared to rats with unchanged behaviour (P , 0.002). There was no significant difference between groups for mean change in free triiodothyronine (fT3) or TSH. There was a correlation between decreased dominance behaviour and decrease in both T4 (r = 0.62, P = 0.009) and fT4 (r = 0.71, P = 0.001), but no correlation with TSH. In a sub-population of rats, decreased thyroid hormones did not result in the expected increased levels of TSH to restore pre-injury levels, nor did they show increased hypothalamic thyrotrophin-releasing hormone mRNA expression, indicating altered hypothalamic-pituitary-thyroid axis regulation. Because T3 availability to the brain is dependent on both circulating T3 and T4, decreased peripheral thyroid hormones may result in changed neural function, as expressed in altered complex behaviours in this sub-population of rats. [source] Neuronal disinhibition in the trigeminal nucleus caudalis in a model of chronic neuropathic painEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2010Yasmina B. Martin Abstract The mechanisms underlying neuropathic facial pain syndromes are incompletely understood. We used a unilateral chronic constriction injury of the rat infraorbital nerve (CCI-IoN) as a facial neuropathic model. Pain-related behavior of the CCI-IoN animals was tested at 8, 15 and 26 days after surgery (dps). The response threshold to mechanical stimulation with von Frey hairs on the injured side was reduced at 15 and 26 dps, indicating the presence of allodynia. We performed unitary recordings in the caudalis division of the spinal trigeminal nucleus (Sp5C) at 8 or 26 dps, and examined spontaneous activity and responses to mechanical and thermal stimulation of the vibrissal pad. Neurons were identified as wide dynamic range (WDR) or low-threshold mechanoreceptive (LTM) according to their response to tactile and/or noxious stimulation. Following CCI-IoN, WDR neurons, but not LTM neurons, increased their spontaneous activity at 8 and 26 dps, and both types of Sp5C neurons increased their responses to tactile stimuli. In addition, the on,off tactile response in neurons recorded after CCI-IoN was followed by afterdischarges that were not observed in control cases. Compared with controls, the response inhibition observed during paired-pulse stimulation was reduced after CCI-IoN. Immunohistochemical studies showed an overall decrease in GAD65 immunoreactivity in Sp5C at 26 dps, most marked in laminae I and II, suggesting that following CCI-IoN the inhibitory circuits in the sensory trigeminal nuclei are depressed. Consequently, our results strongly suggest that disinhibition of Sp5C neurons plays a relevant role in the appearance of allodynia after CCI-IoN. [source] Erythropoietin reduces Schwann cell TNF-,, Wallerian degeneration and pain-related behaviors after peripheral nerve injuryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006W. Marie Campana Abstract Chronic sciatic nerve constriction injury (CCI) induces Wallerian degeneration and exaggerated pain-like behaviors. These effects are mediated in large part by pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-,). In this study, we demonstrate that systemically administered recombinant human erythropoietin (rhEpo) facilitates recovery from chronic neuropathic pain associated with CCI in rats. Because TNF-, has been implicated in the development of pain-related behaviors, we measured TNF-, mRNA at the nerve injury site. Systemically or locally administered rhEpo decreased TNF-, mRNA, compared with that observed in untreated animals. RhEpo also significantly (P < 0.05) decreased axonal degeneration. Immunohistochemistry of CCI nerve showed abundant TNF-, in Schwann cells, axoplasm and macrophages. In rhEpo-treated animals, TNF-, immunopositivity was decreased selectively in Schwann cells. These results suggest a model in which rhEpo counteracts the effects of TNF-, in CCI by blocking expression of TNF-, in Schwann cells. To further test this model, we studied primary Schwann cell cultures. RhEpo inhibited TNF-, expression in response to lipopolysaccharide, supporting the conclusions of our in vivo CCI experiments. In addition, rhEpo directly counteracted Schwann cell death induced by exogenously added TNF-,in vitro. These results indicated that rhEpo regulates TNF-, by multiple mechanisms; rhEpo regulates TNF-, mRNA expression by Schwann cells but also may directly counteract TNF-, signaling pathways that lead to injury, chronic pain and/or death. [source] Schwann cells express erythropoietin receptor and represent a major target for Epo in peripheral nerve injuryGLIA, Issue 4 2005Xiaoqing Li Abstract Erythropoietin (Epo) expresses potent neuroprotective activity in the peripheral nervous system; however, the underlying mechanism remains incompletely understood. In this study, we demonstrate that Epo is upregulated in sciatic nerve after chronic constriction injury (CCI) and crush injury in rats, largely due to local Schwann cell production. In uninjured and injured nerves, Schwann cells also express Epo receptor (EpoR), and its expression is increased during Wallerian degeneration. CCI increased the number of Schwann cells at the injury site and the number was further increased by exogenously administered recombinant human Epo (rhEpo). To explore the activity of Epo in Schwann cells, primary cultures were established. These cells expressed cell-surface Epo receptors, with masses of 71 and 62 kDa, as determined by surface protein biotinylation and affinity precipitation. The 71-kDa species was rapidly but transiently tyrosine-phosphorylated in response to rhEpo. ERK/MAP kinase was also activated in rhEpo-treated Schwann cells; this response was blocked by pharmacologic antagonism of JAK-2. RhEpo promoted Schwann cell proliferation, as determined by BrdU incorporation. Cell proliferation was ERK/MAP kinase-dependent. These results support a model in which Schwann cells are a major target for Epo in injured peripheral nerves, perhaps within the context of an autocrine signaling pathway. EpoR-induced cell signaling and Schwann cell proliferation may protect injured peripheral nerves and promote regeneration. © 2005 Wiley-Liss, Inc. [source] Chronic constriction injury induces aquaporin-2 expression in the dorsal root ganglia of ratsJOURNAL OF ANATOMY, Issue 5 2009Barbara Buffoli Abstract Aquaporins are a family of water channel proteins involved in water homeostasis in several tissues. Current knowledge of aquaporin expression in the nervous system is very limited. Therefore the first aim of this study was to assess, by immunohistochemistry and immunoblotting analysis, the presence and localization of aquaporin-2 in the spinal cord and dorsal root ganglia of naïve adult rats. In addition, we evaluated aquaporin-2 expression in response to chronic constriction injury of the sciatic nerve, a model of neuropathic pain. Our results showed that aquaporin-2 expression was not detectable either in the spinal cord or the dorsal root ganglia of naïve rats. However, we showed for the first time an increase of aquaporin-2 expression in response to chronic constriction injury treatment in small-diameter dorsal root ganglia neurons but no expression in the lumbar spinal cord. These data support the hypothesis that aquaporin-2 expression is involved in inflammatory neuropathic nerve injuries, although its precise role remains to be determined. [source] Neuropathy-induced apoptosis: Protective effect of physostigmineJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2009L. Di Cesare Mannelli Abstract Traumatic, infectious, metabolic, and chemical noxa to the nervous system are the etiology of a crippling disease generally termed neuropathy. Motor disorders, altered sensibility, and pain are the pathognomonic traits. Cellular alterations induced by this chronic pathology include mitochondrial dysfunctions that lead to the activation of the apoptotic cascade. Energy imbalance can compromise the maintenance of mitochondrial membrane potential, furthering the release of cytochrome C and the subsequent cleavage and activation of caspases. Chronic constriction injury (CCI) of the rat sciatic nerve is a neuropathy model able to induce a strong mitochondrial impairment with a consequent apoptotic induction. In this model, the acetylcholinesterase inhibitor physostigmine is administered at 0.125 mg/kg i.p. (twice per day) starting from the operation and for 15 days after. The cholinergic activation reduces cytosolic levels of cytochrome C, suggesting an improved stability of the mitochondrial membrane, and the expression level of the active caspase 3 fragments (19, 16 kDa) is reduced significantly with respect to saline treatment. Accordingly, physostigmine impairs caspase 3 protease activity. In fact, the target of the activated caspase 3, the 89-kDa PARP fragment, is significantly less expressed in the ligated nerve of physostigmine-treated rats, reaching levels that are comparable to those in the contralateral unligated nerve. Finally, this natural acetylcholinesterase inhibitor reduces DNA fragmentation both in the proximal and in the distal parts of the nerve. This protection correlates with the induction of XIAP. Therefore, apoptosis, central to tissue degeneration, is prevented by repeated physostigmine treatment of CCI animals. © 2009 Wiley-Liss, Inc. [source] Etanercept reduces hyperalgesia in experimental painful neuropathyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2001Claudia Sommer Abstract Etanercept, a recombinant tumor necrosis factor receptor (p75)-Fc fusion protein competitively inhibits tumor necrosis factor-alpha (TNF). Etanercept has been successfully used in patients with rheumatoid arthritis, where it reduces pain and inflammation. Because locally produced proinflammatory cytokines play a role in pain after nerve injury, we investigated whether etanercept can reduce pain and hyperalgesia in an animal model of painful neuropathy, the chronic constriction injury of the sciatic nerve. C57BL/6 mice received etanercept or sham treatment by local near-nerve injection to the injured nerve or by systemic application. Treatment with etanercept reduced thermal hyperalgesia and mechanical allodynia significantly in both modes of application. The effect of etanercept was present in animals that were treated from the time of surgery and in those that were treated from day 6, when hyperalgesia was already present. These results suggest the potential of etanercept as a treatment option for patients with neuropathic pain. [source] Painful neuropathy alters the effect of gabapentin on sensory neuron excitability in ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2004A. Kanai Background:, Pain following peripheral nerve injury is associated with increased excitability of sensory neurons. Gabapentin (GBP), a novel anticonvulsant with an uncertain mechanism of action, is an effective treatment for neuropathic pain. We therefore investigated the effect of GBP on dorsal root ganglion (DRG) neurons from normal rats and those with painful peripheral nerve injury. Methods:, Dorsal root ganglions were excised from rats with neuropathic pain behaviour following chronic constriction injury (CCI) of the sciatic nerve, and from normal rats. Intercellular recordings were made from myelinated sensory neuron somata using a microelectrode technique from DRGs bathed in artificial CSF with or without GBP (100 µM). Results:, Compared with normal neurons, injury decreased the refractory interval (RI) for repeat action potential (AP) generation increased the number of APs during sustained depolariza- tion, and shortened the after hyperpolarization following an AP. In normal neurons, GBP decreased the RI and increased the AP number during sustained depolarization. In an opposite fashion, the result of GBP application to injured neurons was a decreased number of APs during depolarization and no change in RI. In injured neurons only, GBP increased the time-to-peak for AP depolarization. Conclusions:, Nerve injury by CCI is associated with increased sensory neuron excitability, associated with a decreased AHP. In normal peripheral sensory neurons, GBP has pro-excitatory effects, whereas GBP decreases excitability in injured neurons, possibly on the basis of altered sodium channel function. [source] | |||||||||||||