Drug Disease Interactions: Role of Inflammatory Mediators in Pain and Variability in Analgesic Drug Response

Kenneth M. Kulmatycki1, Fakhreddin Jamali2

1Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute
2Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta

Abstract


Pain has both physical and emotional components. Physical noxious stimuli activate peripheral sensory neurons that, in turn, relay signals to the spinal and supraspinal nuclei. Subsequently, these signals activate areas within the brain associated with pain. Despite considerable knowledge in this area, analgesics may provide pain complete relief in only one out of five patients. Failure to manage pain may be due to a lack of understanding of the neurobiological processing of pain. Factors such as anticipation, anxiety and pain history play roles in the perception of pain. Non-neuronal cells such as those of the immune system influence perception and modulation of pain by the nervous system. In post-dental surgery patients, the severity of the pain and the relief following administration of anti-inflammatory analgesics has been linked to the time course of inflammatory mediators. Similarly, the relief of post-operative pain after abdominal surgery is also associated with a reduction in expression of pro-inflammatory mediators. Administration of anti-cytokines to sciatica patients and subsequent pain relief further emphasizes the role of pro-inflammatory mediators in modulation of pain. Increased expression of inflammatory mediators may also alter response to analgesia. For example, rheumatoid patients with temporal mandibular joint disease with increased expression of interleukins prior to treatment demonstrate inadequate pain relief after administration of anti-TNF-?. In addition, pain or its trauma impairs absorption of oral analgesics causing therapeutic failure. Improved analgesic pharmacotherapy may require a better understanding of the involvement of the inflammatory pathways.

J Pharm Pharm Sci, 10 (4): 554-566, 2007

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