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overview My research encompasses both basic and clinical research: cardiovascular pharmacology, general anesthetic action, local anesthesia, opioid pharmacology, postoperative analgesia, treatment of chronic pain, pharmacology of vanilloid agonists, and assessment of medical research using specific publication-based indices. Here are several highlights: I developed (1981-1993) the concept that general anesthesia is based not on a single general anesthetic action but on a spectrum of separate pharmacological actions, even if only one drug is used. As a result, the characteristics of an anesthetic agent depend on the relative strength of various independent actions that constitute the components of anesthesia (unconsciousness, absence of movement in response to noxious stimulation, attenuation of autonomic responses, etc.). The development of this concept led to the conclusion that the search for a reliable index of anesthetic depth should be focused on separate indices of the distinct components of anesthesia. One area of my investigations is preemptive analgesia (1990-2002), an intervention which prevents establishment of the altered sensory processing that amplifies post-operative pain. We identified the most important condition for maximizing the preemptive effect: the treatment should cover the entire duration of high-intensity noxious stimulation that can lead to establishment of sensitization including the initial postoperative period. As a result, we suggested the adoption of a different term – “preventive analgesia”. We demonstrated (1991-1998) that acute tolerance to opioid analgesia can develop very rapidly and that this phenomenon carries over into humans, especially with short-acting opioids such as remifentanil. We also demonstrated (1994-1998) that intrathecally administered local anesthetics decrease hypnotic requirements for general anesthetics (and for antinociception above the level of spinal blockade), mostly due to decreased afferent input. We have found (2002-2009) that perineural administration of the vanilloid (TRPV1) agonist resiniferatoxin prevents hyperalgesia in a rat model of postoperative pain. An electron microscopy study in rats also demonstrated that resiniferatoxin-induced sciatic nerve blockade may produce morphological changes in C fibers, but to a much smaller degree than local anesthetics. This result opens a new avenue in the treatment of pain: to use nerve blockade for selective analgesia, analgesia without suppressing motor or sensory functions unrelated to pain. We opened (2011-2016) a new area of scientometrics (studies on quantitative aspects of science): the assessment of medical research using specific publication-based indices. This direction belongs to a category of big data analytics. Presently (2017-2018) we are concentrating on the following topic: "Stagnation in the research related to the pharmacological basis of anesthesia." To assess this problem we are combining three approaches: scientometric analysis of changes in academic interest in this field, assessment of the degree of novelty of new drugs and drug candidates for general and regional anesthesia, and evaluation of advances reported in pertinent meta-analyses.
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.