Arch Neurol. 2003;60:1524-1534.
Robert H. Dworkin, PhD; Miroslav Backonja, MD; Michael C. Rowbotham, MD; Robert R. Allen, MD; Charles R. Argoff, MD; Gary J. Bennett, PhD; M. Catherine Bushnell, PhD; John T. Farrar, MD; Bradley S. Galer, MD; Jennifer A. Haythornthwaite, PhD; David J. Hewitt, MD; John D. Loeser, MD; Mitchell B. Max, MD; Mario Saltarelli, MD, PhD; Kenneth E. Schmader, MD; Christoph Stein, MD; David Thompson, PhD; Dennis C. Turk, PhD; Mark S. Wallace, MD; Linda R. Watkins, PhD; Sharon M. Weinstein, MD
ABSTRACT
Chronic neuropathic pain, caused by lesions in the peripheral or central nervous system, comes in many forms. We describe current approaches to the diagnosis and assessment of neuropathic pain and discuss the results of recent research on its pathophysiologic mechanisms. Randomized controlled clinical trials of gabapentin, the 5% lidocaine patch, opioid analgesics, tramadol hydrochloride, and tricyclic antidepressants provide an evidence-based approach to the treatment of neuropathic pain, and specific recommendations are presented for use of these medications. Continued progress in basic and clinical research on the pathophysiologic mechanisms of neuropathic pain may make it possible to predict effective treatments for individual patients by application of a pain mechanism–based approach. An evidence-based treatment approach is becoming feasible as the number of published randomized controlled trials continues to grow steadily. In this article, we discuss the diagnosis and assessment of neuropathic pain and survey recent research on pathophysiologic mechanisms. Evidence-based treatment recommendations for the pharmacologic management of chronic neuropathic pain are presented that take into account clinical effectiveness, adverse effects, influence on quality of life, and cost.
Free Full Text: http://archneur.ama-assn.org/cgi/content/full/60/11/1524
Showing posts with label mechanism. Show all posts
Showing posts with label mechanism. Show all posts
Friday, October 16, 2009
Monday, September 21, 2009
Molecular genetics of migraine.
Hum Genet. 2009 Jul;126(1):115-32. Epub 2009 May 20.
de Vries B, Frants RR, Ferrari MD, van den Maagdenberg AM.
Department of Human Genetics, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
Migraine is an episodic neurovascular disorder that is clinically divided into two main subtypes that are based on the absence or presence of an aura: migraine without aura (MO) and migraine with aura (MA). Current molecular genetic insight into the pathophysiology of migraine predominantly comes from studies of a rare monogenic subtype of migraine with aura called familial hemiplegic migraine (FHM). Three FHM genes have been identified, which all encode ion transporters, suggesting that disturbances in ion and neurotransmitter balances in the brain are responsible for this migraine type, and possibly the common forms of migraine. Cellular and animal models expressing FHM mutations hint toward neuronal hyperexcitability as the likely underlying disease mechanism. Additional molecular insight into the pathophysiology of migraine may come from other monogenic syndromes (for instance cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which is caused by NOTCH3 mutations), in which migraine is prominent. Investigating patients with common forms of migraine has had limited successes. Except for 5',10'-methylenetetrahydrolate reductase, an enzyme in folate metabolism, the large majority of reported genetic associations with candidate migraine genes have not been convincingly replicated. Genetic linkage studies using migraine subtypes as an end diagnosis did not yield gene variants thus far. Clinical heterogeneity in migraine diagnosis may have hampered the identification of such variants. Therefore, the recent introduction of more refined methods of phenotyping, such as latent-class analysis and trait component analysis, may be certainly helpful. Combining the new phenotyping methods with genome-wide association studies may be a successful strategy toward identification of migraine susceptibility genes. Likely the identification of reliable biomarkers for migraine diagnosing will make these efforts even more successful.
PMID: 19455354 [PubMed - indexed for MEDLINE]
de Vries B, Frants RR, Ferrari MD, van den Maagdenberg AM.
Department of Human Genetics, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
Migraine is an episodic neurovascular disorder that is clinically divided into two main subtypes that are based on the absence or presence of an aura: migraine without aura (MO) and migraine with aura (MA). Current molecular genetic insight into the pathophysiology of migraine predominantly comes from studies of a rare monogenic subtype of migraine with aura called familial hemiplegic migraine (FHM). Three FHM genes have been identified, which all encode ion transporters, suggesting that disturbances in ion and neurotransmitter balances in the brain are responsible for this migraine type, and possibly the common forms of migraine. Cellular and animal models expressing FHM mutations hint toward neuronal hyperexcitability as the likely underlying disease mechanism. Additional molecular insight into the pathophysiology of migraine may come from other monogenic syndromes (for instance cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which is caused by NOTCH3 mutations), in which migraine is prominent. Investigating patients with common forms of migraine has had limited successes. Except for 5',10'-methylenetetrahydrolate reductase, an enzyme in folate metabolism, the large majority of reported genetic associations with candidate migraine genes have not been convincingly replicated. Genetic linkage studies using migraine subtypes as an end diagnosis did not yield gene variants thus far. Clinical heterogeneity in migraine diagnosis may have hampered the identification of such variants. Therefore, the recent introduction of more refined methods of phenotyping, such as latent-class analysis and trait component analysis, may be certainly helpful. Combining the new phenotyping methods with genome-wide association studies may be a successful strategy toward identification of migraine susceptibility genes. Likely the identification of reliable biomarkers for migraine diagnosing will make these efforts even more successful.
PMID: 19455354 [PubMed - indexed for MEDLINE]
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