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1.
Neuroscience ; 114(3): 529-46, 2002.
Article in English | MEDLINE | ID: mdl-12220557

ABSTRACT

Neuropathic pain is induced by injury or disease of the nervous system. Studies aimed at understanding the molecular pathophysiology of neuropathic pain have so far focused on a few known molecules and signaling pathways in neurons. However, the pathophysiology of neuropathic pain appears to be very complex and remains poorly understood. A global understanding of the molecular mechanisms involved in neuropathic pain is needed for a better understanding of the pathophysiology and treatment of neuropathic pain. Towards this end, we examined global gene expression changes as well as the pathobiology at the cellular level in a spinal nerve ligation neuropathic pain model using DNA microarray, quantitative real-time PCR and immunohistochemistry. We found that the behavioral hypersensitivity that is manifested in the persistent pain state is accompanied by previously undescribed changes in gene expression. In the DRG, we found regulation of: (1) immediate early genes; (2) genes such as ion channels and signaling molecules that contribute to the excitability of neurons; and (3) genes that are indicative of secondary events such as neuroinflammation. In addition, we studied gene regulation in both injured and uninjured DRG by quantitative PCR, and observed differential gene regulation in these two populations of DRGs. Furthermore, we demonstrated unexpected co-regulation of many genes, especially the activation of neuroinflammation markers in both the PNS and CNS. The results of our study provide a new picture of the molecular mechanisms that underlie the complexity of neuropathic pain and suggest that chronic pain shares common pathobiology with progressive neurodegenerative disease.


Subject(s)
Gene Expression/physiology , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Pain/metabolism , Pain/pathology , Animals , Chronic Disease , Ganglia, Spinal/injuries , Ganglia, Spinal/metabolism , Ganglia, Spinal/pathology , Ligation , Male , Rats , Rats, Sprague-Dawley , Spinal Cord/metabolism , Spinal Cord/pathology , Spinal Nerves/injuries , Spinal Nerves/metabolism , Spinal Nerves/pathology
2.
Clin Orthop Relat Res ; (384): 116-21, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11249156

ABSTRACT

A retrospective chart review of 68 patients 70 years of age or older who underwent decompressive procedures of the lumbar spine with or without fusion for benign conditions was performed to determine the ability of preoperative assessment of medical comorbidities to predict early postoperative complications. Patients 70 years of age or older who underwent decompressive procedures on the lumbar spine with or without fusion from January 1, 1990 to June 30, 1996 were identified. A chart review focused on preoperative comorbid diseases and early postoperative complications. A telephone survey was performed to assess patient satisfaction. Thirty-four women and 34 men with an average of 76.5 years averaged 1.6 comorbidities. Thirteen patients did not have comorbidities. The weighted comorbidity index resulted in an average score of 1.9. Eighty-five percent of the patients underwent posterolateral fusion. The total complication rate was 40%. Serious complications potentially affecting quality of life occurred in 12% of patients. The early mortality rate was 1.4%. The authors were unable to show a significant relationship between comorbidities and postoperative complications. Seventy-one percent of the 44 patients who were contacted at an average 42 months postoperatively were satisfied with their outcome. Elderly patients can safely undergo lumbar spinal procedures with an outcome similar to younger patients.


Subject(s)
Lumbar Vertebrae/surgery , Postoperative Complications , Spinal Stenosis/surgery , Aged , Comorbidity , Data Collection , Decompression, Surgical/adverse effects , Female , Humans , Male , Patient Satisfaction , Quality of Life , Retrospective Studies , Spinal Stenosis/complications
3.
Clin Orthop Relat Res ; (384): 75-81, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11249182

ABSTRACT

Lumbar spinal decompression is a commonly performed procedure. Although the conventional open techniques of decompression remain the gold standard of treatment, problems with paraspinal musculature denervation and resultant lumbar instability have focused attention on less invasive techniques. A multitude of spinal instrumentation systems have been developed to stabilize the spine and improve arthrodesis rates. A stronger emphasis on restoration of anterior column height and stability has increased the use of anterior interbody fusion devices. Developing technology is allowing for better visualization and possibly improved outcomes with minimally-invasive techniques. The results of all lumbar decompressive and stabilization procedures however, remain closely related to careful patient selection.


Subject(s)
Decompression, Surgical/methods , Lumbar Vertebrae/surgery , Spinal Stenosis/surgery , Diskectomy, Percutaneous , Humans , Internal Fixators , Intervertebral Disc/surgery , Laminectomy/methods , Spinal Fusion/methods
4.
Mol Cell Biochem ; 179(1-2): 147-58, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9543357

ABSTRACT

The time course of force generation and the time course of muscle stiffness were measured in rabbit soleus muscles during eccentric contraction to understand the underlying basis for the force loss in these muscles. Muscles were activated for 600 msec every 10 sec for 30 min. Soleus muscles contracting isometrically maintained constant tension throughout the treatment period, while muscles subjected to eccentric contraction rapidly dropped tension generation by 75% within the first few minutes and then an additional 10% by the end of 30 min. This indicated a dramatic loss in force-generating ability throughout the 30 min treatment period. To estimate the relative number of cross-bridges attached during the isometric force generation phase immediately preceding each eccentric contraction, stiffness was measured during a small stretch of a magnitude equal to 1.5% of the fiber length. Initially, muscle stiffness exceeded 1300 g/mm and, as eccentric treatment progressed, stiffness decreased to about 900 g/mm. Thus, while muscle stiffness decreased by only 30% over the 30 min treatment period, isometric force decreased by 85%. In isometrically activated muscles, stiffness remained constant throughout the treatment period. These data indicate that, while soleus muscles decreased their force generating capability significantly, there were a number of cross-bridges still attached that were not generating force. In summary, the loss of force generating capacity in the rabbit soleus muscle appears to be related to a fundamental change in myosin cross-bridge properties without the more dramatic morphological changes observed in other eccentric contraction models. These results are compared and contrasted with the observations made on muscles composed primarily of fast fibers.


Subject(s)
Isometric Contraction/physiology , Muscle, Skeletal/pathology , Animals , Biomechanical Phenomena , Immunohistochemistry , Models, Biological , Muscle Proteins/metabolism , Myosins/metabolism , Rabbits
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