ABSTRACT
Chronic pain is one of the most reported health problems in patients suffering from spinal cord injuries and is described by the patients as one of the most burdensome sequelae of paraplegia. Various types of pain, such as nociceptive, neuropathic and other types of pain can occur. In addition, multiple pathophysiological mechanisms based on the biopsychosocial pain model play a role in the origins of the pain. These aspects necessitate a multimodal pain management approach in this patient group. This article presents an overview of the occurrence, importance and pathophysiology of chronic pain following spinal cord injury as well as diagnostic and therapeutic approaches.
Subject(s)
Chronic Pain/diagnosis , Pain Measurement , Paraplegia/diagnosis , Brain/physiopathology , Chronic Pain/physiopathology , Chronic Pain/therapy , Combined Modality Therapy , Humans , Interdisciplinary Communication , Intersectoral Collaboration , Neuralgia/diagnosis , Neuralgia/physiopathology , Neuralgia/therapy , Nociceptors/physiology , Paraplegia/physiopathology , Paraplegia/therapy , Peripheral Nerves/physiopathology , Psychology , Risk Factors , Spinal Cord/physiopathology , Spinal Nerve Roots/physiopathologyABSTRACT
The oxidative capacity of cat skeletal muscles (soleus, gracilis, and gracilis chronically stimulated for 28 days) was derived from the total mitochondrial content in the muscle, the surface area of mitochondrial inner membranes, and respiratory activities of isolated mitochondria. Mitochondrial content was estimated by standard morphometry. The surface area of mitochondrial inner membranes per unit volume of mitochondria was estimated by a stereological method. The respiratory activities of isolated mitochondria were measured biochemically, using pyruvate/malate, glutamate/malate, succinate, or cytochrome c as substrate. Structurally and functionally, mitochondria from the three muscle types showed nearly identical characteristics. Oxidative activity was dependent on substrate; with succinate, 5.8 ml of O2 per min per ml of mitochondria was the rate most likely to represent physiological conditions. Oxidative activities of 3.1 ml.min-1.ml-1 with pyruvate/malate and 14.5 ml.min-1.ml-1 with cytochrome c as substrates were theoretical lower and upper bounds. The oxidative capacity of each of the three muscles was thus in direct proportion to the total volume of mitochondria in the muscle. The respiratory capacity of isolated mitochondria was very near to the maximal oxygen uptake rate of mitochondria that is commonly estimated in intact muscles of a wide variety of animals.
Subject(s)
Mitochondria, Muscle/physiology , Muscles/physiology , Oxygen Consumption , Animals , Cats , Electric Stimulation , Female , Kinetics , Microscopy, Electron , Mitochondria, Muscle/metabolism , Mitochondria, Muscle/ultrastructure , Muscle Contraction , Organ Specificity , Reference ValuesABSTRACT
A morphometric analysis was performed on horse muscle tissue to quantify mitochondrial distribution relative to capillaries. Samples of M. vastus medialis, M. semitendinosus, M. masseter and M. cutaneus thoracicus were preserved in a glutaraldehyde fixative for electron microscopy, or frozen for biochemical and histochemical analysis. These four muscles varied from highly oxidative in type, consisting nearly completely of type I fibres, in masseter, to highly glycolytic, primarily type IIb fibres, in cutaneus. In all four muscles, mitochondria were found in highest volume density near capillaries at the fibre border, with a sharp decline in volume density towards the fibre centre. This distribution was independent of myoglobin concentration, muscle fibre type and the activities of three key metabolic enzymes, citrate synthase, 3-OH-acyl-CoA dehydrogenase and lactate dehydrogenase.
Subject(s)
Horses/metabolism , Mitochondria, Muscle/metabolism , Oxygen Consumption , 3-Hydroxyacyl CoA Dehydrogenases/metabolism , Animals , Citrate (si)-Synthase/metabolism , L-Lactate Dehydrogenase/metabolism , Microscopy, Electron , Mitochondria, Muscle/ultrastructure , Muscles/anatomy & histology , Organ SpecificityABSTRACT
The mitochondrial ATP synthase/ATPase (F0F1 ATPase) is perhaps the most complex enzyme known. In animal systems it consists of a minimum of 11 different polypeptide chains, 10 (or more) of which appear to be essential for function, and 1 called the "ATPase inhibitor peptide" which is involved in regulation. Recent studies from a variety of laboratories indicate that the ATP synthase/ATPase complex is regulated by several interrelated factors including the thermodynamic poise of the proton gradient across the inner mitochondrial membrane; the ATPase inhibitor peptide; ADP (and/or ADP and Pi); divalent cations; and perhaps the redox state of SH groups on the F1 molecule. The central focus of this review is the ATPase inhibitor peptide. A model involving four distinct conformational states of F1 seems essential to account for the inhibitor's mode of action. The model depicts the ATPase inhibitor protein as acting at the asymmetric center of the F1 moiety. In addition, it accounts for the "unidirectional" role of the inhibitor peptide as a "down regulator" of ATP hydrolysis and for its binding/debinding dependence on the proton motive force and other regulatory factors. Finally, it is suggested that during any physiological process, where there is an energy demand followed by a resting phase, the F1 molecule may follow a "cyclic" path involving the four distinct conformational states of the enzyme.
Subject(s)
Mitochondria/enzymology , Proteins/physiology , Proton-Translocating ATPases/antagonists & inhibitors , Animals , Binding Sites , Electron Transport , Models, Chemical , Protein Binding , Proton-Translocating ATPases/metabolism , ATPase Inhibitory ProteinABSTRACT
The molecular structure of mitochondria and their inner membrane has been studied using a combined approach of stereology and biochemistry. The amount of mitochondrial structures (volume, number, surface area of inner membrane) in a purified preparation of mitochondria from rat liver was estimated by stereological procedures. In the same preparation, the oxidative activity of the respiratory chain with different substrates and the concentration of the redox complexes were measured by biochemical means. By relating the stereological and biochemical data, it was estimated that the individual mitochondrion isolated from rat liver has a volume of 0.27 micron 3, an inner membrane area of 6.5 micron 2, and contains between 2,600 (complex I) and 15,600 (aa3) redox complexes which produce an electron flow of over 100,000 electrons per second with pyruvate as substrate. The individual redox complexes and the H+-ATPase together occur at a density of approximately 7,500/micron 2 and occupy approximately 40% of the inner membrane area. From the respective densities it was concluded that the mean nearest distance between reaction partners is small enough (70-200 A) to cause the formation of micro-aggregates. The meaning of these results for the mechanism of mitochondrial energy transduction is discussed.
Subject(s)
Intracellular Membranes/ultrastructure , Mitochondria, Liver/ultrastructure , Animals , Cytochromes/metabolism , Electron Transport , Male , Microscopy, Electron/methods , Mitochondria, Liver/metabolism , Oxygen Consumption , Proton-Translocating ATPases/metabolism , RatsSubject(s)
Affinity Labels/chemical synthesis , Azides/chemical synthesis , Cross-Linking Reagents/chemical synthesis , Mitochondria, Liver/enzymology , Proteins/metabolism , Proton-Translocating ATPases/antagonists & inhibitors , Animals , Azides/metabolism , Carbon Radioisotopes , Kinetics , Radioisotope Dilution Technique , Rats , ATPase Inhibitory ProteinABSTRACT
The binding of calmodulin to the mitochondrial F1.F0-ATPase has been studied. [125I]Iodoazidocalmodulin binds to the epsilon-subunit and to the endogeneous ATPase inhibitor peptide in a Ca2+-dependent reaction. The effect of the mitochondrial ATPase inhibitor peptide on the purified Ca2+-ATPase of erythrocytes has also been analyzed. The inhibitor peptide stimulates the ATPase when pre-incubated with the enzyme. The activation of the Ca2+-ATPase by calmodulin is not influenced by the inhibitor peptide, indicating that the two mechanisms of activation are different. These in vitro effects of the two regulatory proteins may reflect a common origin of the two ATPases considered and/or of the regulatory proteins.
Subject(s)
Adenosine Triphosphatases/antagonists & inhibitors , Calcium-Transporting ATPases/blood , Calmodulin/metabolism , Erythrocytes/enzymology , Mitochondria/enzymology , Proteins/pharmacology , Animals , Binding Sites/drug effects , Calmodulin/pharmacology , Cattle , Enzyme Activation/drug effects , Imidazoles/pharmacology , In Vitro Techniques , Protein Binding/drug effects , Proteins/metabolism , Proton-Translocating ATPases , Rats , ATPase Inhibitory ProteinSubject(s)
Adenosine Triphosphatases/metabolism , Azides , Mitochondria, Liver/enzymology , Proteins/metabolism , Adenosine Triphosphatases/antagonists & inhibitors , Animals , Chromatography, Gel , Cross-Linking Reagents , Male , Proteins/isolation & purification , Proton-Translocating ATPases , Rats , Tissue Distribution , ATPase Inhibitory ProteinSubject(s)
Adenosine Triphosphatases/antagonists & inhibitors , Adenosine Triphosphate/metabolism , Mitochondria, Liver/enzymology , Proteins/pharmacology , Animals , Intracellular Membranes/enzymology , Kinetics , Male , Models, Chemical , NAD/metabolism , Proton-Translocating ATPases , Rats , ATPase Inhibitory ProteinSubject(s)
Adenosine Triphosphatases/metabolism , Mitochondria, Liver/enzymology , Oxidative Phosphorylation Coupling Factors/metabolism , Proteins/metabolism , Adenosine Triphosphate/metabolism , Animals , Kinetics , Male , Proteins/isolation & purification , Proton-Translocating ATPases , Rats , ATPase Inhibitory ProteinABSTRACT
Phosphoenolpyruvate carboxykinase showed high activity in Saccharomyces cerevisiae grown on gluconeogenic carbon sources. Addition of glucose to such cultures caused a rapid loss of the phosphoenolpyruvate carboxykinase activity. Fructose or mannose had the same effect as glucose, while 2-deoxyglucose or galactose were without effect. The inactivation was an irreversible process, since the regain of the activity was dependent of de novo protein synthesis. Cycloheximide did not prevent inactivation. All strains of the genus Saccharomyces tested showed inactivation of their phosphoenolpyruvate carboxykinase upon addition of glucose; this behaviour was not restricted to this genus.