BSCB Newsletter, Spring 2008

Society for Neuroscience
3–7 November, 2007. San Diego Convention Center

The 37th annual meeting of the Society for Neuroscience was held from the 3rd – 7th November 2007 in San Diego, California.  With over 30000 people attending, this conference can be a particularly daunting prospect.  However, having attended the previous meeting in Atlanta in 2006, I had a better idea of what to expect and how to prepare myself for the vast poster sessions that lay ahead.

On the first day we were welcomed by glorious sunshine and an impressive venue: the San Diego Convention Center. As previously, the conference was well organised and registration went smoothly, allowing attendees to get straight into the first poster sessions.  My research is focussed on the neuroscience of pain and I was pleased to see several poster sessions dedicated to aspects of this field on each day of the conference. 

The first session included two interesting posters from Jeff Mogil’s Pain Genetics Lab (McGill University), whose research investigates the relationship between genetics, the environment and pain. Following their paper examining the effect of empathy on pain in mice (Langford et al., 2006), they presented research looking at the same phenomenon in humans.  Painful thermal stimuli were applied to the back of the hand and pain intensity and unpleasantness was quantified using the visual analogue scale (VAS).  Feelings of empathy were generated by showing subjects one of two recorded interviews of an actor which were designed to elicit either high or low empathy feelings, which were also rated.  The high empathy group showed increased pain scores (both sensory and affective) when given painful but not non-painful thermal stimulation, demonstrating that compassion can increase pain perception in humans. 

They also presented data investigating the impact of the presence of a human experimenter during behavioural pain testing using the formalin test. Administration of formalin to the hind paw produced characteristic pain behaviours that were scored from video footage. They observed that the presence of an experimenter in the room while the behaviour was being recorded had an analgesic effect, i.e. less pain behaviours were observed. Further experiments provided evidence showing that this effect was directly due to the presence of a pair of eyes in the room and was opioid-mediated and testosterone-linked and is likely to be due to stress-induced analgesia and may be predator-related. These findings may impact the way behavioural tests are performed and demonstrate that in some cases it could be more appropriate to use female mice, where this response was absent.

On Sunday morning there was an interesting seminar from George Walker, Director of the Carnegie Initiative on the Doctorate (CID), detailing the work the CID has done with a wide range of neuroscience departments across America to improve the way PhD programmes are run.  This innovative project aimed to engage departments in a process of self-discovery to assess whether they were producing doctorate researchers who not only possessed the technical expertise to become good scientific researchers but also developed a range of other skills including the ability to mentor, to critically review the work of others, to develop collaborations and to drive their own research forward.

My research centres on the role of acid signalling in pain, particularly that which is mediated by acid-sensing ion channels (ASICs). These ion channels are also implicated in other neurological roles and ASIC1a knockout mice have an anxiolytic phenotype.  Jason Dwyer (Wyeth Research) demonstrated that ASIC antagonists, particularly those specific for ASIC1a, had anxiolytic effects in a range of behavioural models in mice and that these effects may be mediated by an increase in the inhibitory neurotransmitter GABA in the amygdala. Therefore ASIC1a presents a novel target for the development of anxiolytic compounds. This was further supported by data from John Wemmie’s lab (University of Iowa) showing that the normally anxiolytic ASIC1a knockout mouse had increased fear conditioning when an adenoassociated virus 1 was used to induce ASIC1a expression in the amygdala, demonstrating the importance of this brain region for the modulation of anxiety levels.  A second poster from this group suggested that ASIC1a in the amygdala may respond to protons released either from synaptic vesicles or due generalised brain acidosis in a model of CO2 inhalation.  In this model, the ASIC1a knockout strain again showed reduced anxiety-like behaviours.

On Monday, data from Candice Askwith’s lab (Thomas Sherwood, Ohio State University) demonstrated further evidence of peptide modulation of ASIC currents by RFamides. Non-activating decreases in pH can lead to steady-state desensitisation of ASIC currents and enhancement of this phenomenon may be neuroprotective in circumstances such as ischaemia.  This steady-state desensitisation is inhibited by RFamides and this inhibition is dependent on channel subtype.

Apkar Vania Apkarian (Northwestern University) chaired Tuesday morning’s symposium titled “The Brain in Chronic Pain”, which showed how improvements in brain imaging techniques have been applied to chronic pain research.  Karen Davis (Toronto Western Research Institute) described the complexities of studying functional diseases, where often no structural pathologies are apparent, and how fMRI can be used to try and reveal neurobiological abnormalities in patients affected by such diseases.  She went on to look at the relationship between pain and attention and the role of personality in altering pain perception.  Finally she commented on the factors that must be addressed before fMRI can be used as a diagnostic tool, particularly the determination of ‘normal’ brain activity and how abnormalities could be defined.  Irene Tracey (Oxford University) went on to further describe the role of the brainstem in central sensitisation and chronic pain.  She also discussed the pharmacological challenges faced by the pain field and championed the need for reverse translation of fMRI based research techniques back into animal models as a way to help produce drugs for the treatment of chronic pain.

I presented my poster on the modulation of visceral inflammatory pain by acid-sensing ion channels on Tuesday afternoon and I was really encouraged by the amount of interest it generated.  I had some very fruitful discussion with scientists from a range of fields and some of the challenging questions addressed will certainly help me in writing my PhD thesis!

On the final morning I was pleased to be able to attend a minisymposium dedicated to the “Emerging Roles of Acid-Sensing Ion Channels in Neurological and Psychiatric Disorders” chaired by John Dunlop (Wyeth Research) and John Wemmie (University of Iowa).  Candice Askwith (Ohio State University) opened the session with further data showing modulation of ASIC1a steady state desensitisation (SSD) by peptides.  She also showed that the ASIC1a-specific toxin Psalmotoxin 1 (PcTx1) has its antagonistic effects by enhancing SSD, but if SSD is not induced by small, non-activating decreases in pH then PcTx1 can actually enhance ASIC1a currents.  Further work comparing mouse and human ASIC1a channels showed that a larger population of endogenous peptides were able to interact with human ASIC1a to inhibit SSD, suggesting that blockade of these peptides would have greater neuroprotective effects in humans than research using mice models suggests. 

Zhigang Xiong (Legacy Research) described the lack of success of NMDA receptor antagonists in treating ischaemic cell death and the potential role of ASIC1a in glutamate-independent calcium toxicity.  Acidosis occurs during ischaemia due to anaerobic metabolism and this can cause neuronal injury via activation of ASIC1a and entry of calcium into neurones.  Neuronal death after ischaemia is reduced in ASIC1a knockout mice and also when using the ASIC1a antagonist PcTx1 and this antagonist has a longer time window for treatment that glutamate antagonists.

Manual Friese (Oxford University) showed interesting new data on the role of ASICs in a mouse model of multiple sclerosis (MS).  Using the experimental autoimmune encephalitis (EAE) model of autoimmune CNS inflammation, he demonstrated that physical disability correlated best with axonal degeneration rather than demyelination.  ASIC1a was again implicated in the process as the inflammatory environment has an acidic pH which may cause ASIC1a activation, allowing calcium entry leading to cell death.  The ASIC1a subtype was protected from behavioural changes associated with EAE even though the inflammation that occurred was equivalent to that seen in wild type animals.  These changes were accompanied by a profound drop in neuronal number that was reduced in ASIC1a knockout mice and after treatment with PcTx1.  These exciting findings suggest that ASIC1a may be an important target for preventing disease progression in MS and clinical trials are planned to assess this. 

This minisymposium was a great way to end the conference, highlighting the diverse roles that acid-sensing ion channels play in neurological function and giving me ideas for where I would like to take my research in the future.  Presenting my own data at SfN was also a rewarding and valuable experience and the feedback I received will be very useful in completing my thesis and in my final viva!

Amelia Staniland
London Pain Consortium
King’s College London