Please click below for webinar outlines and confirmed speakers
Chair: Dr Nicholas Veldhuis, Monash Institute of Pharmaceutical Sciences, VIC
With ongoing challenges in clinical opioid use, basic research in pain and molecular pharmacology of opioids continues to be valuable for improving our understanding of opioid mechanisms of action. This session will discuss some of the signalling processes that drive opioid efficacy and poor safety profiles at the molecular and cellular level, with the goal of revealing new insights that may be of interest to basic researchers and clinical researchers alike. This will be also be linked to discussion around attempts pharma have made (generally without success) to improve the therapeutic index of opioids and will conclude with a panel discussion with all 4 speakers to engage the audience in this topical session.
A/Professor Peter Grace, University of Texas, USA
Dr Daniel Poole, Monash Institute of Pharmaceutical Sciences, VIC
Professor Macdonald Christie, University of Sydney, NSW
Professor Paul Rolan, University of Adelaide, SA
|Why is it important who shares our genes, our nociceptors, our reactions?I will argue that it matters very much, because it helps us to understand the function of many mechanisms that we now understand well. How we came to be how we are is not the result of steady progress towards perfection, as some people represent evolution, but of many minor changes – some of which add up to major changes, and many of which have unexpected effects – shaped by the environment in which we lived. Evolutionary thinking can give us new ways of conceptualising a wide range of concerns in pain, from behavioural tests on experimental animals (do they really indicate pain?), to how behaviour changes in the presence of ongoing central sensitisation (with similarities across squid, mice and humans). Some evolutionary hypotheses are testable, and others can be approximated in mathematical models: it is not all armchair speculation. The findings have implications for animal welfare, and for preventing and mitigating chronic pain in humans in particular.|
|Tuesday 27 July 2021, 10.00am - 11.00am AEST
Imaging cortical activity during general anesthesia: preclinical insights into cortical pain processing
Speaker: Professor Allan Basbaum, University California San Francisco, USA
|General anesthetics work in a concentration-dependent manner on the central nervous system (CNS) to induce loss of consciousness and block the experience of pain. Interestingly, however, during nitrous oxide anesthesia and the initial stages of ether and isoflurane anesthesia, analgesia can be produced independently of loss of consciousness. In fact, the classical description of stages of anesthesia described an analgesic stage, followed by an amnesia stage, during which a patient could speak to the anesthesiologist, but have no memory of the event. Only in the last stage was unconsciousness produced. With a view to identifying cortical neuronal activity patterns that correlate with these different stages, especially the analgesic stage, we have now monitored, over time, the in vivo activity of hundreds of individual cortical neurons in the anterior cingulate cortex (ACC) during the induction to, and emergence from, general anesthesia in the mouse. Furthermore, we compared the effects of anesthetics on bulk neural activity (pan-neuronally) versus isolated subpopulations of molecularly-defined cortical inhibitory interneurons (parvalbumin (PV+), somatostatin (SST+) or vasointestinal peptide (VIP+)). Spontaneous neural activity was continuously monitored before, during, and after isoflurane or nitrous oxide anesthesia. Most importantly, behavioral testing can be performed during induction and recovery from anesthesia.|
We used virally delivered genetically encoded fluorescent reporters of neural activity (GCaMP6f) expressed either (1) ubiquitously across neurons, or (2) specifically within molecularly-defined interneuron populations (PV+, SST+, or VIP+). We monitored GCaMP6f fluorescence captured via Inscopix miniscopes. During induction and emergence, we found that inhibitory interneuron populations are most susceptible to the suppression of neural activity by isoflurane than the bulk population. During induction, both spontaneous neural activity and the percentage of active neurons decreases with increasing concentrations of isoflurane, however, inhibitory neurons are affected at much lower concentrations of isoflurane than the bulk population. Similarly, during emergence, neural activity resumes in at much higher concentrations of isoflurane for the bulk neural population than for inhibitory interneurons. Unexpectedly, although ablation of the ACC reportedly reduces the affective pain experience, nitrous oxide, an analgesic agent, dramatically increased ACC neuronal activity. Ongoing studies are addressing the circuits engaged by this enhanced activity.
Tuesday 31 August 2021, 6.00pm - 7.00pm AEST
Pain and pleasure are powerful motivators of behaviour, and are often viewed as opposite and mutually inhibitory. People are expected to seek pleasure and avoid pain. This perspective is however most suitable for the short term. Throughout life, people seek challenges even when there is a high risk of pain, and overcoming painful challenges can yield pleasure for instance by increasing the experience of a meaningful life (eudaimonia). Acute pain can also increase hedonic pleasure, e.g. through contrast or attentional mechanisms. Notably, such beneficial effects of pain or near-pain are typically limited to pain that is perceived as controllable.
These potential beneficial effects of the pain experience are unlikely to arise from more long-lasting pain. Indeed, the high comorbidity between chronic pain and affective disorders led my collaborators and I to expect some degree of anhedonia in people with chronic pain.
In two studies, we addressed this question using ratings of hedonic capacity from a commonly used anhedonia questionnaire, the Snaith-Hamilton Pleasure Scale. We find evidence for significantly higher anhedonia in people with chronic pain with and without concurrent treatment with analgesia (Garland et al, 2019, Psychol Med). When opioid-treated patients were classified according to misuse status, those who used prescription opioids in other ways than prescribed (misusers) showed significantly higher analgesia than opioid users. Compared to anhedonia scores from other clinical groups however, the available chronic pain samples showed only moderate anhedonia, comparable to scores reported for Parkinson’s Disease, substance use disorder and schizophrenia. In contrast, people with active depressive episodes displayed high anhedonia which is likely to differ both qualitatively and quantitatively from anhedonia in chronic pain (Trøstheim et al, 2020, JAMA Network Open). Reviewing evidence from these and other studies, we tentatively conclude that anhedonia in chronic pain exists partly independent from comorbid depression, and that alleviating anhedonia may be a promising avenue for treatment of chronic pain.