Person:

Kissin, Igor

Background: Surgical injury can frequently lead to chronic pain. Despite the obvious importance of this problem, the first publications on chronic pain after surgery as a general topic appeared only a decade ago. This study tests the hypothesis that chronic postsurgical pain was, and still is, represented insufficiently. Methods: We analyzed the presentation of this topic in journal articles covered by PubMed and in surgical textbooks. The following signs of insufficient representation in journal articles were used: (1) the lack of journal editorials on chronic pain after surgery, (2) the lack of journal articles with titles clearly indicating that they are devoted to chronic postsurgical pain, and (3) the insufficient representation of chronic postsurgical pain in the top surgical journals. Results: It was demonstrated that insufficient representation of this topic existed in 1981–2000, especially in surgical journals and textbooks. Interest in this topic began to increase, however, mostly regarding one specific surgery: herniorrhaphy. It is important that the change in the attitude toward chronic postsurgical pain spreads to other groups of surgeries. Conclusion: Chronic postsurgical pain is still a neglected topic, except for pain after herniorrhaphy. The change in the attitude toward chronic postsurgical pain is the important first step in the approach to this problem.

The annual number of US deaths from prescription-opioid overdose quadrupled between 1999 and 2010 and in 2010 alone reached 16,651. Deaths from opioid overdose have now surpassed the historic death toll from another drug-related epidemic – anesthesia mortality. In 1954, Beecher and Todd published reliable data on anesthesia-related mortality in the US, estimating the annual number of deaths to be nearly 5,000. Presently anesthesia/anesthetics are reported as the underlying cause in approximately 34 deaths in the US annually. This spectacular decline in anesthesia-related mortality could serve as an example for attempts to curb the epidemic of opioid overdose death. The main reason that led to the dramatic decline in anesthesia-related mortality is the context in which anesthetics are used. It includes training of the anesthesia providers, the introduction of specific standards of patient safety, and anesthesia monitoring. I suggest that the introduction of a similar multifactorial proper context for the use of opioids in the treatment of chronic nonmalignant pain might be the same “game changer” it was for safety in anesthesia.

The aim of this study was to find signs of progress in the pharmacotherapy of chronic pain over the past 35 years using scientometric analysis. The following scientometric indices were used: 1) popularity index, representing the share of articles on a specific drug(s) relative to all articles in the field of chronic pain; 2) index of change, representing the degree of growth in publications on a topic from one period to the next; 3) index of expectations, representing the ratio of the number of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed; and 4) index of ultimate success, representing a publication outcome when a new drug takes the place of a common drug previously used for the same purpose. Publications on 55 drugs used in the treatment of chronic pain were assessed during seven 5-year periods, from 1979 to 2013. The rate of rise in the number of publications on chronic pain was exponential, with an increase of nearly ninefold from 2,346 articles over the 5-year period 1979–1983 to 21,095 articles in 2009–2013. However, despite this huge increase in publications, our scientometric analysis did not reveal signs of really successful drugs in this field. For the 2009–2013 period, the popularity index had a meaningful magnitude (from 0.5–2.8) for only 13 of 55 drugs. Five of them were opioids, including morphine, which had the highest index value of all drugs (2.8). None of the drugs had a high index of expectations in 2009–2013. The index of ultimate success was positive only with triptans in the relatively limited area of acute treatment of migraine. As a result, despite rapid growth in the number of publications, our scientometric analysis did not reveal signs of substantial progress in the field of pharmacotherapy for chronic pain.

The aim of this study was to assess progress in the field of anesthetic drugs over the past 30 years using scientometric indices: popularity indices (general and specific), representing the proportion of articles on a drug relative to all articles in the field of anesthetics (general index) or the subfield of a specific class of anesthetics (specific index); index of change, representing the degree of growth in publications on a topic from one period to the next; index of expectations, representing the ratio of the number of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed; and index of ultimate success, representing a publication outcome when a new drug takes the place of a common drug previously used for the same purpose. Publications on 58 topics were assessed during six 5-year periods from 1984 to 2013. Our analysis showed that during 2009–2013, out of seven anesthetics with a high general popularity index (≥2.0), only two were introduced after 1980, ie, the inhaled anesthetic sevoflurane and the local anesthetic ropivacaine; however, only sevoflurane had a high index of expectations (12.1). Among anesthetic adjuncts, in 2009–2013, only one agent, sugammadex, had both an extremely high index of change (>100) and a high index of expectations (25.0), reflecting the novelty of its mechanism of action. The index of ultimate success was positive with three anesthetics, ie, lidocaine, isoflurane, and propofol, all of which were introduced much longer than 30 years ago. For the past 30 years, there were no new anesthetics that have produced changes in scientometric indices indicating real progress.

Background: For the past 30 years, opioids have been used to treat chronic nonmalignant pain. This study tests the following hypotheses: (1) there is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective; and (2) the main problem associated with the safety of such treatment – assessment of the risk of addiction – has been neglected. Methods: Scientometric analysis of the articles representing clinical research in this area was performed to assess (1) the quality of presented evidence (type of study); and (2) the duration of the treatment phase. The sufficiency of representation of addiction was assessed by counting the number of articles that represent (1) editorials; (2) articles in the top specialty journals; and (3) articles with titles clearly indicating that the addiction-related safety is involved (topic-in-title articles). Results: Not a single randomized controlled trial with opioid treatment lasting >3 months was found. All studies with a duration of opioid treatment ≥6 months (n = 16) were conducted without a proper control group. Such studies cannot provide the consistent good-quality evidence necessary for a strong clinical recommendation. There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general. An inadequate number of chronic pain-related publications were observed with all three types of counted articles: editorials, articles in the top specialty journals, and topic-in-title articles. Conclusion: There is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective. The above identified signs indicating neglect of addiction associated with the opioid treatment of chronic nonmalignant pain were present.

Over the past 2 decades, many new techniques and drugs for the treatment of acute pain have achieved widespread use. The main aim of this study was to assess the progress in their implementation using scientometric analysis. The following scientometric indices were used: 1) popularity index, representing the share of articles on a specific technique (or a drug) relative to all articles in the field of acute pain; 2) index of change, representing the degree of growth in publications on a topic compared to the previous period; and 3) index of expectations, representing the ratio of the number of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed. Publications on specific topics (ten techniques and 21 drugs) were assessed during four time periods (1993–1997, 1998–2002, 2003–2007, and 2008–2012). In addition, to determine whether the status of routine acute pain management has improved over the past 20 years, we analyzed surveys designed to be representative of the national population that reflected direct responses of patients reporting pain scores. By the 2008–2012 period, popularity index had reached a substantial level (≥5%) only with techniques or drugs that were introduced 30–50 years ago or more (epidural analgesia, patient-controlled analgesia, nerve blocks, epidural analgesia for labor or delivery, bupivacaine, and acetaminophen). In 2008–2012, promising (although modest) changes of index of change and index of expectations were found only with dexamethasone. Six national surveys conducted for the past 20 years demonstrated an unacceptably high percentage of patients experiencing moderate or severe pain with not even a trend toward outcome improvement. Thus, techniques or drugs that were introduced and achieved widespread use for acute pain management within the past 20 years have produced no changes in scientometric indices that would indicate real progress and have failed to improve national outcomes for relief of acute pain. Two possible reasons for this are discussed: 1) the difference between the effectiveness of old and new techniques is not clinically meaningful; and 2) resources necessary for appropriate use of new techniques in routine pain management are not adequate.

The Top Journal Selectivity Index (TJSI) is a scientometric index reflecting the potential importance of a new drug. It represents the ratio of the number of all types of articles on a particular drug in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by Medline over the 5 years since the drug’s introduction. The TJSI can be an indicator of a drug’s potential for sustained use: a higher score increases the probability of continuing success.

The aim of this study was to make a scientometric assessment of drug discovery efforts centered on pain-related molecular targets. The following scientometric indices were used: the popularity index, representing the share of articles (or patents) on a specific topic among all articles (or patents) on pain over the same 5-year period; the index of change, representing the change in the number of articles (or patents) on a topic from one 5-year period to the next; the index of expectations, representing the ratio of the number of all types of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed over a 5-year period; the total number of articles representing Phase I–III trials of investigational drugs over a 5-year period; and the trial balance index, a ratio of Phase I–II publications to Phase III publications. Articles (PubMed database) and patents (US Patent and Trademark Office database) on 17 topics related to pain mechanisms were assessed during six 5-year periods from 1984 to 2013. During the most recent 5-year period (2009–2013), seven of 17 topics have demonstrated high research activity (purinergic receptors, serotonin, transient receptor potential channels, cytokines, gamma aminobutyric acid, glutamate, and protein kinases). However, even with these seven topics, the index of expectations decreased or did not change compared with the 2004–2008 period. In addition, publications representing Phase I–III trials of investigational drugs (2009–2013) did not indicate great enthusiasm on the part of the pharmaceutical industry regarding drugs specifically designed for treatment of pain. A promising development related to the new tool of molecular targeting, ie, monoclonal antibodies, for pain treatment has not yet resulted in real success. This approach has not yet demonstrated clinical effectiveness (at least with nerve growth factor) much beyond conventional analgesics, when its potential cost is more than an order of magnitude higher than that of conventional treatments. This scientometric assessment demonstrated a lack of real breakthrough developments.

Background: Previous studies found that rats subjected to carrageenan injection develop hyperalgesia, and despite complete recovery in several days, they continue to have an enhanced hyperalgesic response to a new noxious challenge for more than 28d. The study's aim was to identify candidate genes that have a role in the formation of the long-term hyperalgesia-related imprint in the spinal cord. This objective was undertaken with the understanding that the long-lasting imprint of acute pain in the central nervous system may contribute to the transition of acute pain to chronicity. Results: To analyze changes in gene expression when carrageenan-induced hyperalgesia has disappeared but propensity for the enhanced hyperalgesic response is still present, we determined the gene expression profile using oligo microarray in the lumbar part of the spinal cord in three groups of rats: 28d after carrageenan injection, 24h after injection (the peak of inflammation), and with no injection (control group). Out of 17,000 annotated genes, 356 were found to be differentially expressed compared with the control group at 28d, and 329 at 24h after carrageenan injection (both groups at (p \lt 0.01)). Among differentially expressed genes, 67 (39 in 28d group) were identified as being part of pain-related pathways, altered in different models of pain, or interacting with proteins involved in pain-related pathways. Using gene ontology (GO) classification, we have identified 3 functional classes deserving attention for possible association with pain memory: They are related to cell-to-cell interaction, synaptogenesis, and neurogenesis. Conclusion: Despite recovery from inflammatory hyperalgesia, persistent changes in spinal cord gene expression may underlie the propensity for the enhanced hyperalgesic response. We suggest that lasting changes in expression of genes involved in the formation of new synapses and neurogenesis may contribute to the transition of acute pain to chronicity.

The aim of this study was to assess progress in the field of anesthesia monitoring over the past 40 years using scientometric analysis. The following scientometric indexes were used: popularity indexes (general and specific), representing the proportion of articles on either a topic relative to all articles in the field of anesthetics (general popularity index, GPI) or the subfield of anesthesia monitoring (specific popularity index, SPI); index of change (IC), representing the degree of growth in publications on a topic from one period to the next; and index of expectations (IE), representing the ratio of the number of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed. Publications on 33 anesthesia-monitoring topics were assessed. Our analysis showed that over the past 40 years, the rate of rise in the number of articles on anesthesia monitoring was exponential, with an increase of more than eleven-fold, from 296 articles over the 5-year period 1974–1978 to 3,394 articles for 2009–2013. This rise profoundly exceeded the rate of rise of the number of articles on general anesthetics. The difference was especially evident with the comparison of the related GPIs: stable growth of the GPI for anesthesia monitoring vs constant decline in the GPI for general anesthetics. By the 2009–2013 period, among specific monitoring topics introduced after 1980, the SPI index had a meaningful magnitude (≥1.5) in 9 of 24 topics: Bispectral Index (7.8), Transesophageal Echocardiography (4.2), Electromyography (2.8), Pulse Oximetry (2.4), Entropy (2.3), Train-of-four (2.3), Capnography (1.9), Pulse Contour (1.9), and Electrical Nerve Stimulation for neuromuscular monitoring (1.6). Only one of these topics (Pulse Contour) demonstrated (in 2009–2013) high values for both IC and IE indexes (76 and 16.9, respectively), indicating significant recent progress. We suggest that rapid growth in the field of anesthetic monitoring was one of the most important developments to compensate for the intrinsically low margins of safety of anesthetic agents.