Mechanism-based pain diagnosis - Issues for analgesic drug development

Harvard University, Cambridge, Massachusetts, United States
Anesthesiology (Impact Factor: 6.17). 08/2001; 95(1):241-9. DOI: 10.1097/00000542-200107000-00034
Source: PubMed
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    • "Clinical pain management should be based on a relational classification system of pain [16]. Recent studies suggest that QST may be useful in differential diagnosis , including detection of hypersensitivity and other pathogenesis of pain [4] [5] [7] [17]. "
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    ABSTRACT: Accurate assessment of pain or sensory function in clinical practice is challenging. Quantitative Sensory Testing (QST) is a standardized approach to measuring pain and sensory thresholds or tolerances as a means of assessing the functionality of neural pathways from the receptors along the afferent fibers to the brains. This paper reviews two simple QST techniques potentially useful to clinical practice: the Cold Stress Test and Ten Test. The background, evidence for clinical measurement properties and feasibility issues are considered. Keywords Quantitative evaluation, sensory test, pain, sensation, threshold
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    • "A precise diagnosis is critical to the development of more effective treatments that are tailored to specific underlying mechanisms. Because neuropathic pain is dependent on multiple mechanisms [26], this knowledge gap is a significant barrier to translation of basic research finding into successful management of neuropathic pain. The determination of clinical pain phenotypes is a promising way to classify pain types. "
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    ABSTRACT: Treatment of sensory neuropathies, whether inherited or caused by trauma, the progress of diabetes, or other disease states, are among the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord would be the logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the transplant of cells or a cell line to treat human disease. The history of the research and development of useful cell-transplant-based approaches offers an understanding of the advantages and problems associated with these technologies, but as an adjuvant or replacement for current pharmacological treatments, cell therapy is a likely near future clinical tool for improved health care.
    06/2012; 2012:263972. DOI:10.1155/2012/263972
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    • "If a particular patient's pain is primarily the result of abnormal activity in nociceptors, as in patients with primary erythromelalgia [74], the optimal therapy required is likely to be different from a patient whose tactile allodynia and secondary hyperalgesia are entirely maintained by central sensitization due to changes in synaptic efficacy in the spinal cord. This is the rationale for a mechanism-based approach to the diagnosis and treatment of pain [258] [266]. Indeed response to a trial treatment, such as to the NMDA receptor antagonist ketamine, can itself be a potential diagnostic for the presence central sensitization. "
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    ABSTRACT: Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.
    Pain 10/2010; 152(3 Suppl):S2-15. DOI:10.1016/j.pain.2010.09.030 · 5.84 Impact Factor