Woolf CJ, Max MB: Mechanism-based pain diagnosis: Issues for analgesic drug development

Harvard University, Cambridge, Massachusetts, United States
Anesthesiology (Impact Factor: 5.88). 08/2001; 95(1):241-9. DOI: 10.1097/00000542-200107000-00034
Source: PubMed
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    • "This peripheral-central interaction dictates that therapeutic effects in the periphery will also have a secondary influence on the neuroplastic changes of nociceptive transmission in the central nervous system (CNS). Surprisingly little is currently known about the effect of pharmacotherapy and other treatment strategies on the central mechanisms of pain and inflammation in humans [79]. "
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    ABSTRACT: Non-opioid agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the anti-hyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in pre- and post-surgical states, and looked at the analgesic interaction between surgical state and treatment. We used an established clinical pain model involving third molar extraction (TME), and quantitative arterial spin labelling (ASL) imaging to measure changes in tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual analogue scales (VAS) inside the scanner to evaluate the subjective experience of pain. This novel methodology was incorporated into a randomized, double-blind placebo-controlled design, with an open method of drug administration. We found that independent of its antinociceptive action, ibuprofen has no effect on regional cerebral blood flow (rCBF) under pain-free conditions (pre-surgery). However, in the post-surgical state, we observed increased activation of top-down modulatory circuits which was accompanied by decreases in the areas engaged due to ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain-relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Pain 04/2015; 156(7). DOI:10.1097/j.pain.0000000000000176 · 5.21 Impact Factor
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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
    Physiotherapy Practice and Research 03/2014; 35(1):33-40. DOI:10.3233/PPR-130030
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    • "Finding better preclinical testing methods is critical for more effective development of novel analgesics. Until now, the track record of rational drug development in the field of analgesics [5] has not been very convincing. Most of the new analgesics have originally been developed for other indications, and it has been argued that none of the analgesic drugs in clinical use at present is a result of a truly rational development program. "
    Scandinavian Journal of Pain 10/2013; 4(4):224–225. DOI:10.1016/j.sjpain.2013.07.025
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