Abstract:
:Chronic pain can occur after peripheral nerve injury, infection, or inflammation. Under such neuropathic pain conditions, sensory processing in the affected body region becomes grossly abnormal. Despite decades of research, currently available drugs largely fail to control such pain. This review explores the possibility that the reason for this failure lies in the fact that such drugs were designed to target neurons rather than immune or glial cells. It describes how immune cells are a natural and inextricable part of skin, peripheral nerves, dorsal root ganglia, and spinal cord. It then examines how immune and glial activation may participate in the etiology and symptomatology of diverse pathological pain states in both humans and laboratory animals. Of the variety of substances released by activated immune and glial cells, proinflammatory cytokines (tumor necrosis factor, interleukin-1, interleukin-6) appear to be of special importance in the creation of peripheral nerve and neuronal hyperexcitability. Although this review focuses on immune modulation of pain, the implications are pervasive. Indeed, all nerves and neurons regardless of modality or function are likely affected by immune and glial activation in the ways described for pain.
journal_name
Physiol Revjournal_title
Physiological reviewsauthors
Watkins LR,Maier SFdoi
10.1152/physrev.00011.2002subject
Has Abstractpub_date
2002-10-01 00:00:00pages
981-1011issue
4eissn
0031-9333issn
1522-1210journal_volume
82pub_type
杂志文章,评审abstract::The anterior pituitary gland has the ability to respond to complex signals derived from central and peripheral systems. Perception of these signals and their integration are mediated by cell interactions and cross-talk of multiple signaling transduction pathways and transcriptional regulatory networks that cooperate f...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00003.2011
更新日期:2012-01-01 00:00:00
abstract::Endothelial cells (ECs) are more than inert blood vessel lining material. Instead, they are active players in the formation of new blood vessels (angiogenesis) both in health and (life-threatening) diseases. Recently, a new concept arose by which EC metabolism drives angiogenesis in parallel to well-established angiog...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00001.2017
更新日期:2018-01-01 00:00:00
abstract::The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is now recognized to play a central role in pathological events in the cardiovascular system. CaMKII has diverse downstream targets that promote vascular disease, heart failure, and arrhythmias, so improved understanding of CaMKII signalin...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00018.2010
更新日期:2011-07-01 00:00:00
abstract::The last 10 years have witnessed a surge of interest for the mechanisms underlying the acquisition and extinction of classically conditioned fear responses. In part, this results from the realization that abnormalities in fear learning mechanisms likely participate in the development and/or maintenance of human anxiet...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00037.2009
更新日期:2010-04-01 00:00:00
abstract::The 1910-1913 Terra Nova Expedition to the Antarctic, led by Captain Robert Falcon Scott, was a venture of science and discovery. It is also a well-known story of heroism and tragedy since his quest to reach the South Pole and conduct research en route, while successful was also fateful. Although Scott and his four co...
journal_title:Physiological reviews
pub_type: 传,历史文章,杂志文章
doi:10.1152/physrev.00031.2011
更新日期:2012-04-01 00:00:00
abstract::Mitogen-activated protein kinases (MAPK) are serine-threonine protein kinases that are activated by diverse stimuli ranging from cytokines, growth factors, neurotransmitters, hormones, cellular stress, and cell adherence. Mitogen-activated protein kinases are expressed in all eukaryotic cells. The basic assembly of MA...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1999.79.1.143
更新日期:1999-01-01 00:00:00
abstract::Small GTPases use GDP/GTP alternation to actuate a variety of functional switches that are pivotal for cell dynamics. The GTPase switch is turned on by GEFs, which stimulate dissociation of the tightly bound GDP, and turned off by GAPs, which accelerate the intrinsically sluggish hydrolysis of GTP. For Ras, Rho, and R...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00003.2012
更新日期:2013-01-01 00:00:00
abstract::Astrocytes are the most abundant cells in the central nervous system (CNS) that provide nutrients, recycle neurotransmitters, as well as fulfill a wide range of other homeostasis maintaining functions. During the past two decades, astrocytes emerged also as increasingly important regulators of neuronal functions inclu...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00041.2013
更新日期:2014-10-01 00:00:00
abstract::The transepithelial movement of fluids, electrolytes, and larger molecules is achieved by the activity of a host of specialized transporting proteins, including enzymes, receptors, and channels, that are located on either the apical, basal, or lateral plasma membrane domains of epithelial cells. In the kidney as well ...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1996.76.1.245
更新日期:1996-01-01 00:00:00
abstract::Intercellular calcium (Ca(2+)) waves (ICWs) represent the propagation of increases in intracellular Ca(2+) through a syncytium of cells and appear to be a fundamental mechanism for coordinating multicellular responses. ICWs occur in a wide diversity of cells and have been extensively studied in vitro. More recent stud...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00029.2011
更新日期:2012-07-01 00:00:00
abstract::The cone snails (genus Conus) are venomous marine molluscs that use small, structured peptide toxins (conotoxins) for prey capture, defense, and competitor deterrence. Each of the 500 Conus can express approximately 100 different conotoxins, with little overlap between species. An overwhelming majority of these peptid...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00020.2003
更新日期:2004-01-01 00:00:00
abstract::Traditionally the auditory system was considered a hard-wired sensory system; this view has been challenged in recent years in light of the plasticity of other sensory systems, particularly the visual and somatosensory systems. Practical experience in clinical audiology together with the use of prosthetic devices, suc...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00002.2002
更新日期:2002-07-01 00:00:00
abstract::Afferent signals that guide orienting movements converge in the deeper layers of the SC in a wide variety of animals. The sensory cells are arranged topographically according to their receptive-field locations and, thereby, form maps of sensory space. Maps of visual, somatosensory, and/or auditory space have been obta...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1986.66.1.118
更新日期:1986-01-01 00:00:00
abstract::Hemoglobin (Hb) occurs in all the kingdoms of living organisms. Its distribution is episodic among the nonvertebrate groups in contrast to vertebrates. Nonvertebrate Hbs range from single-chain globins found in bacteria, algae, protozoa, and plants to large, multisubunit, multidomain Hbs found in nematodes, molluscs a...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.2001.81.2.569
更新日期:2001-04-01 00:00:00
abstract::Although opioids are highly effective for the treatment of pain, they are also known to be intensely addictive. There has been a massive research investment in the development of opioid analgesics, resulting in a plethora of compounds with varying affinity and efficacy at all the known opioid receptor subtypes. Althou...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.2001.81.1.299
更新日期:2001-01-01 00:00:00
abstract::While transport processes for amino acids and glucose have long been known to be expressed in the luminal and abluminal membranes of the endothelium comprising the blood-brain and blood-retinal barriers, it is only within the last decades that endothelial and smooth muscle cells derived from peripheral vascular beds h...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00022.2002
更新日期:2003-01-01 00:00:00
abstract::This review focuses on the intricate properties of the glomerular barrier. Other reviews have focused on podocyte biology, mesangial cells, and the glomerular basement membrane (GBM). However, since all components of the glomerular membrane are important for its function, proteinuria will occur regardless of which lay...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00055.2006
更新日期:2008-04-01 00:00:00
abstract::The neuromuscular junction is the chemical synapse between motor neurons and skeletal muscle fibers. It is designed to reliably convert the action potential from the presynaptic motor neuron into the contraction of the postsynaptic muscle fiber. Diseases that affect the neuromuscular junction may cause failure of this...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00033.2014
更新日期:2015-07-01 00:00:00
abstract::Vascular smooth muscle cells (VSMC) exhibit several growth responses to agonists that regulate their function including proliferation (hyperplasia with an increase in cell number), hypertrophy (an increase in cell size without change in DNA content), endoreduplication (an increase in DNA content and usually size), and...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.2001.81.3.999
更新日期:2001-07-01 00:00:00
abstract::Impairments of vision and hearing are highly prevalent conditions limiting the quality of life and presenting a major socioeconomic burden. For a long time, retinal and cochlear disorders have remained intractable for causal therapies, with sensory rehabilitation limited to glasses, hearing aids, and electrical cochle...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00035.2019
更新日期:2020-10-01 00:00:00
abstract::The distal tubule of the mammalian kidney, defined as the region between the macula densa and the collecting duct, is morphologically and functionally heterogeneous. This heterogeneity has stymied attempts to define functional properties of individual cell types and has led to controversy concerning mechanisms and reg...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.2000.80.1.277
更新日期:2000-01-01 00:00:00
abstract::Polymers of deoxyhemoglobin S deform sickle cell anemia red blood cells into sickle shapes, leading to the formation of dense, dehydrated red blood cells with a markedly shortened life-span. Nearly four decades of intense research in many laboratories has led to a mechanistic understanding of the complex events leadin...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00052.2003
更新日期:2005-01-01 00:00:00
abstract::Dendritic cells (DCs) are bone marrow-derived cells of both lymphoid and myeloid stem cell origin that populate all lymphoid organs including the thymus, spleen, and lymph nodes, as well as nearly all nonlymphoid tissues and organs. Although DCs are a moderately diverse set of cells, they all have potent antigen-prese...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00023.2001
更新日期:2002-01-01 00:00:00
abstract::The life history of fibroblast and fibroblast-like cells includes an initial stage of outgrowth and establishment in culture; a period of vigorous proliferation which has a variable length, depending on the tissue of origin, age of the donor, etc.; a period of declining proliferative vigor which includes substantial c...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1993.73.3.617
更新日期:1993-07-01 00:00:00
abstract::This review summarizes the receptor-mediated vascular activities of calcitonin gene-related peptide (CGRP) and the structurally related peptide adrenomedullin (AM). CGRP is a 37-amino acid neuropeptide, primarily released from sensory nerves, whilst AM is produced by stimulated vascular cells, and amylin is secreted f...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00037.2003
更新日期:2004-07-01 00:00:00
abstract::The function and survival of all organisms is dependent on the dynamic control of energy metabolism, when energy demand is matched to energy supply. The AMP-activated protein kinase (AMPK) alphabetagamma heterotrimer has emerged as an important integrator of signals that control energy balance through the regulation o...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00011.2008
更新日期:2009-07-01 00:00:00
abstract::Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of pos...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.2000.80.4.1523
更新日期:2000-10-01 00:00:00
abstract::Molecular research on ion channels has demonstrated that many of these integral membrane proteins associate with partner proteins, often versatile in their function, or even assemble into stable macromolecular complexes that ensure specificity and proper rate of the channel-mediated signal transduction. Calcium-activa...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00049.2009
更新日期:2010-10-01 00:00:00
abstract::In the last few years there has been a veritable explosion of knowledge about cyclic nucleotide phosphodiesterases. In particular, the accumulating data showing that there are a large number of different phosphodiesterase isozymes have triggered an equally large increase in interest about these enzymes. At least seven...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1995.75.4.725
更新日期:1995-10-01 00:00:00
abstract::The birth of molecular cardiology can be traced to the development and implementation of high-fidelity genetic approaches for manipulating the heart. Recombinant viral vector-based technology offers a highly effective approach to genetically engineer cardiac muscle in vitro and in vivo. This review highlights discover...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00039.2007
更新日期:2008-10-01 00:00:00