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      Investigational pharmacology for low back pain

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          Abstract

          Study design:

          Review and reinterpretation of existing literature.

          Objective:

          This review article summarizes the anatomy and pathogenesis of disease processes that contribute to low back pain, and discusses key issues in existing therapies for chronic low back pain. The article also explains the scientific rationale for investigational pharmacology and highlights emerging compounds in late development.

          Results/conclusion:

          While the diverse and complex nature of chronic low back pain continues to challenge clinicians, a growing understanding of chronic low back pain on a cellular level has refined our approach to managing chronic low back pain with pharmacology. Many emerging therapies with improved safety profiles are currently in the research pipeline and will contribute to a multimodal therapeutic algorithm in the near future. With the heterogeneity of the patient population suffering from chronic low back pain, the clinical challenge will be accurately stratifying the optimal pharmacologic approach for each patient.

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          Most cited references 47

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          Neuronal plasticity: increasing the gain in pain.

          We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is not homogeneous, however, and comprises three categories: physiological, inflammatory, and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an expression of neural plasticity-the capacity of neurons to change their function, chemical profile, or structure. Here, we develop a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain, identifying distinct forms of plasticity, which we term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity.
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            An introduction to TRP channels.

            The aim of this review is to provide a basic framework for understanding the function of mammalian transient receptor potential (TRP) channels, particularly as they have been elucidated in heterologous expression systems. Mammalian TRP channel proteins form six-transmembrane (6-TM) cation-permeable channels that may be grouped into six subfamilies on the basis of amino acid sequence homology (TRPC, TRPV, TRPM, TRPA, TRPP, and TRPML). Selected functional properties of TRP channels from each subfamily are summarized in this review. Although a single defining characteristic of TRP channel function has not yet emerged, TRP channels may be generally described as calcium-permeable cation channels with polymodal activation properties. By integrating multiple concomitant stimuli and coupling their activity to downstream cellular signal amplification via calcium permeation and membrane depolarization, TRP channels appear well adapted to function in cellular sensation. Our review of recent literature implicating TRP channels in neuronal growth cone steering suggests that TRPs may function more widely in cellular guidance and chemotaxis. The TRP channel gene family and its nomenclature, the encoded proteins and alternatively spliced variants, and the rapidly expanding pharmacology of TRP channels are summarized in online supplemental material.
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              • Article: not found

              Expenditures and health status among adults with back and neck problems.

              Back and neck problems are among the symptoms most commonly encountered in clinical practice. However, few studies have examined national trends in expenditures for back and neck problems or related these trends to health status measures. To estimate inpatient, outpatient, emergency department, and pharmacy expenditures related to back and neck problems in the United States from 1997 through 2005 and to examine associated trends in health status. Age- and sex-adjusted analysis of the nationally representative Medical Expenditure Panel Survey (MEPS) from 1997 to 2005 using complex survey regression methods. The MEPS is a household survey of medical expenditures weighted to represent national estimates. Respondents were US adults (> 17 years) who self-reported back and neck problems (referred to as "spine problems" based on MEPS descriptions and International Classification of Diseases, Ninth Revision, Clinical Modification definitions). Spine-related expenditures for health services (inflation-adjusted); annual surveys of self-reported health status. National estimates were based on annual samples of survey respondents with and without self-reported spine problems from 1997 through 2005. A total of 23 045 respondents were sampled in 1997, including 3139 who reported spine problems. In 2005, the sample included 22 258 respondents, including 3187 who reported spine problems. In 1997, the mean age- and sex-adjusted medical costs for respondents with spine problems was $4695 (95% confidence interval [CI], $4181-$5209), compared with $2731 (95% CI, $2557-$2904) among those without spine problems (inflation-adjusted to 2005 dollars). In 2005, the mean age- and sex- adjusted medical expenditure among respondents with spine problems was $6096 (95% CI, $5670-$6522), compared with $3516 (95% CI, $3266-$3765) among those without spine problems. Total estimated expenditures among respondents with spine problems increased 65% (adjusted for inflation) from 1997 to 2005, more rapidly than overall health expenditures. The estimated proportion of persons with back or neck problems who self-reported physical functioning limitations increased from 20.7% (95% CI, 19.9%-21.4%) to 24.7% (95% CI, 23.7%-25.6%) from 1997 to 2005. Age- and sex-adjusted self-reported measures of mental health, physical functioning, work or school limitations, and social limitations among adults with spine problems were worse in 2005 than in 1997. In this survey population, self-reported back and neck problems accounted for a large proportion of health care expenditures. These spine-related expenditures have increased substantially from 1997 to 2005, without evidence of corresponding improvement in self-assessed health status.
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                Author and article information

                Journal
                J Pain Res
                Journal of Pain Research
                Journal of pain research
                Dove Medical Press
                1178-7090
                2010
                06 September 2010
                : 3
                : 169-181
                Affiliations
                [1 ]Department of Physical Medicine and Rehabilitation
                [2 ]Department of Physical Medicine and Rehabilitation, University of Pittsburgh Medical Center, Pittsburgh, PA, USA;
                [3 ]New Jersey Sports Medicine Institute; Overlook Hospital; Mountainside Hospital; Rehabilitation Medicine and Electrodiagnosis, St Michael’s Medical Center; Horizon Healthcare Worker’s Compensation Services, Blue Cross and Blue Shield Worker’s Compensation, Summit, NJ, USA
                Author notes
                Correspondence: Gary P Chimes, Department of Physical Medicine and Rehabilitation, University of Pittsburgh Medical Center, Pittsburgh, PA, USA, Tel +1 412 858 0337, Fax +1 412 372 1493, Email garypchimes@ 123456gmail.com
                Article
                jpr-3-169
                10.2147/JPR.S9243
                3004649
                21197321
                © 2010 Chimes et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Categories
                Review

                Anesthesiology & Pain management

                low back pain, investigational, pharmacology, drugs

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