Although most patients with chronic pain are women, the preclinical literature regarding pain processing and the pathophysiology of chronic pain has historically been derived overwhelmingly from the ...study of male rodents. This Review describes how the recent adoption by a number of funding agencies of policies mandating the incorporation of sex as a biological variable into preclinical research has correlated with an increase in the number of studies investigating sex differences in pain and analgesia. Trends in the field are analysed, with a focus on newly published findings of qualitative sex differences: that is, those findings that are suggestive of differential processing mechanisms in each sex. It is becoming increasingly clear that robust differences exist in the genetic, molecular, cellular and systems-level mechanisms of acute and chronic pain processing in male and female rodents and humans.
A clear majority of patients with chronic pain are women; however, it has been surprisingly difficult to determine whether this sex bias corresponds to actual sex differences in pain sensitivity. A ...survey of the currently available epidemiological and laboratory data indicates that the evidence for clinical and experimental sex differences in pain is overwhelming. Various explanations for this phenomenon have been given, ranging from experiential and sociocultural differences in pain experience between men and women to hormonally and genetically driven sex differences in brain neurochemistry.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The translatability of pain across species Mogil, Jeffrey S
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
11/2019, Letnik:
374, Številka:
1785
Journal Article
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The poor translational record of pain research has suggested to some observers that species differences in pain biology might be to blame. In this review, I consider the evidence for species ...similarity and differences in the pain research literature. Impressive feats of translation have been demonstrated in relation to certain genetic effects, social modulation of pain and pain memory. The degree to which pain biology in rodents predicts pain biology in humans has important implications both for evolutionary accounts of pain, but also the success of analgesic drug development going forward. This article is part of the Theo Murphy meeting issue 'Evolution of mechanisms and behaviour important for pain'.
The social domain of the biopsychosocial model of pain has been greatly understudied compared with the biological and psychological domains but holds great promise for furthering our understanding, ...and better treatment, of pain. Recent years have seen an explosion of interest in social neuroscience and have revealed the ability of pain stimuli to alter social interactions. These experiments suggest that rodents are capable of producing simplified versions of any number of social phenomena involving empathy, previously thought to be the sole province of human beings. This review describes the state of science in both humans and nonhuman animals, and notes intriguing parallels in observations from both species. Indeed, my laboratory is starting to demonstrate perfectly translatable findings regarding social modulation of pain in rodents and humans.
Many are frustrated with the lack of translational progress in the pain field, in which huge gains in basic science knowledge obtained using animal models have not led to the development of many new ...clinically effective compounds. A careful re-examination of animal models of pain is therefore warranted. Pain researchers now have at their disposal a much wider range of mutant animals to study, assays that more closely resemble clinical pain states, and dependent measures beyond simple reflexive withdrawal. However, the complexity of the phenomenon of pain has made it difficult to assess the true value of these advances. In addition, pain studies are importantly affected by a wide range of modulatory factors, including sex, genotype and social communication, all of which must be taken into account when using an animal model.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Preclinical researchers confront two overarching agendas related to drug development: selecting interventions amid a vast field of candidates, and producing rigorous evidence of clinical promise for ...a small number of interventions. We suggest that each challenge is best met by two different, complementary modes of investigation. In the first (exploratory investigation), researchers should aim at generating robust pathophysiological theories of disease. In the second (confirmatory investigation), researchers should aim at demonstrating strong and reproducible treatment effects in relevant animal models. Each mode entails different study designs, confronts different validity threats, and supports different kinds of inferences. Research policies should seek to disentangle the two modes and leverage their complementarity. In particular, policies should discourage the common use of exploratory studies to support confirmatory inferences, promote a greater volume of confirmatory investigation, and customize design and reporting guidelines for each mode.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sex differences in neuroimmunity and pain Rosen, Sarah; Ham, Boram; Mogil, Jeffrey S.
Journal of neuroscience research,
January/February 2017, Letnik:
95, Številka:
1-2
Journal Article
Chronic pain is a classic example of gene × environment interaction: inflammatory and/or nerve injuries are known or suspected to be the etiology of most chronic pain syndromes, but only a small ...minority of those subjected to such injuries actually develop chronic pain. Once chronic pain has developed, pain severity and analgesic response are also highly variable among individuals. Although animal genetics studies have been ongoing for over two decades, only recently have comprehensive human twin studies and large-scale association studies been performed. Here, I review recent and accelerating progress in, and continuing challenges to, the identification of genes contributing to such variability. Success in this endeavor will hopefully lead to both better management of pain using currently available therapies and the development and/or prioritizing of new ones.
We recently demonstrated the utility of quantifying spontaneous pain in mice via the blinded coding of facial expressions. As the majority of preclinical pain research is in fact performed in the ...laboratory rat, we attempted to modify the scale for use in this species. We present herein the Rat Grimace Scale, and show its reliability, accuracy, and ability to quantify the time course of spontaneous pain in the intraplantar complete Freund's adjuvant, intraarticular kaolin-carrageenan, and laparotomy (post-operative pain) assays. The scale's ability to demonstrate the dose-dependent analgesic efficacy of morphine is also shown. In addition, we have developed software, Rodent Face Finder®, which successfully automates the most labor-intensive step in the process. Given the known mechanistic dissociations between spontaneous and evoked pain, and the primacy of the former as a clinical problem, we believe that widespread adoption of spontaneous pain measures such as the Rat Grimace Scale might lead to more successful translation of basic science findings into clinical application.
Pain is an immense clinical and societal challenge, and the key to understanding and treating it is variability. Robust interindividual differences are consistently observed in pain sensitivity, ...susceptibility to developing painful disorders, and response to analgesic manipulations. This review examines the causes of this variability, including both organismic and environmental sources. Chronic pain development is a textbook example of a gene-environment interaction, requiring both chance initiating events (e.g., trauma, infection) and more immutable risk factors. The focus is on genetic factors, since twin studies have determined that a plurality of the variance likely derives from inherited genetic variants, but sex, age, ethnicity, personality variables, and environmental factors are also considered.
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