Neuroscience
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The cholinergic system plays important roles in neurotransmission in both the peripheral and central nervous systems. The cholinergic neurotransmitter acetylcholine is synthesized by choline acetyltransferase (ChAT) and its action terminated by acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The predominance of AChE has focused much attention on understanding the relationship of this enzyme to ChAT-positive cholinergic neurons. ⋯ BuChE-positive neurons without ChAT were found in close proximity with ChAT-positive neuropil in areas such as the thalamus and amygdala. BuChE-positive neuropil was also found closely associated with ChAT-positive neurons, particularly in tegmental nuclei of the pons. These observations provide further neuroanatomical evidence of a role for BuChE in the regulation of acetylcholine levels in the CNS.
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The phosphorylation of p38 mitogen-activated protein kinase (MAPK) in the dorsal root ganglion (DRG) promotes primary afferent sensitization. The role of p38MAPK signaling in the DRG in the pathogenesis of plantar incision hyperalgesia has not been investigated. ⋯ p38MAPK signaling in the DRG plays a crucial role in the development of primary afferent sensitization and pain behavior caused by plantar incision.
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This study investigated the involvement of the adenosinergic system in antiallodynia induced by exercise in an animal model of complex regional pain syndrome type I (CRPS-I). Furthermore, we analyzed the role of the opioid receptors on exercise-induced analgesia. Ischemia/reperfusion (IR) mice, nonexercised and exercised, received intraperitoneal injections of caffeine (10mg/kg, a non selective adenosine receptor antagonist), 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (0.1mg/kg, a selective adenosine A receptor antagonist), ZM241385 (3mg/kg, a selective adenosine A receptor antagonist), adenosine deaminase inhibitor erythro-9-(2-hydroxy-3nonyl) adenine [(EHNA), 5mg/kg, an adenosine deaminase inhibitor] or naloxone (1mg/kg, a nonselective opioid receptor antagonist). ⋯ In addition, treatment with EHNA, which suppresses the breakdown of adenosine to inosine, enhanced the pain-relieving effects of the high-intensity swimming exercise. This is the first report demonstrating that repeated sessions of high-intensity swimming exercise attenuate mechanical allodynia in an animal model of CRPS-I and that the mechanism involves endogenous adenosine and adenosine A receptors. This study supports the use of high-intensity exercise as an adjunct therapy for CRPS-I treatment.
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Long-term potentiation (LTP) can be induced by electrical stimulation and gives rise to an increase in synaptic strength at the first relay. This phenomenon has been associated with learning and memory and also could be the origin of several pathological states elicited by an initial strong painful stimulus, such as some forms of neuropathic pain. We used high-frequency electrical stimulation of the sciatic nerve in anesthetized rats to produce spinal LTP. ⋯ Furthermore, after 3h of LTP induction, PoT neurons could respond to cutaneous stimulation applied to different paws. Interestingly, the conduction velocities for the receptive field responses from the paw to the PoT cells were compatible with those of Aδ-fibers. Since PoT cells project to the insular cortex, the progressive increase in PoT activity and also the progressive unmasking of somatic receptive fields in response to LTP, place these cells in a key position to detect pain stimuli following central sensitization.
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Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. ⋯ Prolonged agmatine treatment improved animals' performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats.