Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0184567 (acute pain)
 3,962 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenylyl cyclase types 1 (AC1) and 8 (AC8), the two major calmodulin-stimulated adenylyl cyclases in the brain, couple NMDA receptor activation to cAMP signaling pathways. Cyclic AMP signaling pathways are important for many brain functions, such as learning and memory, drug addiction, and development. Here we show that wild-type, AC1, AC8, or AC1&8 double knockout (DKO) mice were indistinguishable in tests of acute pain, whereas behavioral responses to peripheral injection of two inflammatory stimuli, formalin and complete Freund's adjuvant, were reduced or abolished in AC1&8 DKO mice. AC1 and AC8 are highly expressed in the anterior cingulate cortex (ACC), and contribute to inflammation-induced activation of CREB. Intra-ACC administration of forskolin rescued behavioral allodynia defective in the AC1&8 DKO mice. Our studies suggest that AC1 and AC8 in the ACC selectively contribute to behavioral allodynia.
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PMID:Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases. 1244 Oct 59

Neurons and synapses in the central nervous systems are very dynamic and plastic, and can undergo changes throughout life. Studies of molecular and cellular mechanisms of such changes not only provide important insight into how we learn and store new knowledge in our brains, but also reveal the mechanisms of pathological changes occurring following an injury. Here, we propose that while neuronal mechanisms underlying physiological functions such as learning and memory may share some common signalling molecules with abnormal or injury-related changes in the brain, distinct synaptic mechanisms are involved in pathological pain as compared with that of cognitive learning and memory. Using genetically altered mice and classic physiological approaches, we showed that N-methyl-D-aspartate (NMDA) receptor-dependent, calcium-calmodulin-activated adenylyl cyclases (AC1 and AC8) in the anterior cingulate cortex (ACC) play important roles in the induction and expression of persistent inflammatory and neuropathic pain. In contrast, acute pain was not significantly affected. Calcium-calmodulin-dependent protein kinase IV, which is widely expressed in central areas related to pain and memory, primarily contributes to injury-related fearful memory and emotional responses. Our studies suggest distinct signalling pathways are responsible for physiological responses to the injury, including behavioural, emotional and memory.
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PMID:Central plasticity in pathological pain. 1546 48

Fear-conditioned analgesia (FCA) is modulated by brain areas involved in the descending inhibitory pain pathway such as the basolateral (BLA) and central amygdala (CEA). The BLA contains Ca2+/calmodulin-dependent protein kinase II (CaMKII) and parvalbumin (PV) neurons. CEA neurons are primarily inhibitory (GABAergic) that comprise enkephalin (ENK) interneurons and corticotropin-releasing factor (CRF) - neurons that project to the periaqueductal grey. The purpose of our experiment was to determine the pattern of activation of CaMKII/PV and ENK/CRF neurons following the expression of acute pain, conditioned fear, and FCA. A significant reduction was observed in nociceptive behaviors in mice re-exposed to a contextually-aversive environment. Using NeuN and cFos as markers for activated neurons, CaMKII, PV, ENK, or CRF were used to identify neuronal subtypes. We find that mice expressing conditioned fear displayed an increase in c-Fos/CaMKII co-localization in the lateral amygdala and BLA compared to controls. Additionally a significant increase in cFos/CRF co-localization was observed in mice expressing FCA. These results show that amygdala processing of conditioned contextual aversive, nociceptive, and FCA behaviors involve different neuronal phenotypes and neural circuits between, within, and from various amygdala nuclei. This information will be important in developing novel therapies for treating pain and emotive disorders in humans.
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PMID:Distinct neuronal populations in the basolateral and central amygdala are activated with acute pain, conditioned fear, and fear-conditioned analgesia. 2891