Sunday, December 31st


Topical Workshop



Mutual Facilitation of Pain and Emotional Dysregulation – Recent Advances of Understanding in Rodents and Human Patients with Major Depression

This workshop will elucidate mechanisms of pain and emotional dysregulation interactions in rodents and humans. Min Zhuo will detail two forms of long-term potentiation (LTP) in the anterior cingulate cortex (ACC), presynaptic LTP requiring kainate receptors and postsynaptic LTP requiring NMDA receptors. Cortical LTPs contribute to chronic pain and anxiety. Inhibiting cortical LTP may aid drug development for future treatment of chronic pain and anxiety. Gal Richter-Levin focuses on emotional symptoms and their contribution to animal pain experience and significant individual variability of co-morbidity following spinal nerve ligation. Even if neuropathic pain remains unchanged cannabinoids reduce emotional symptoms. Thus, pain-related emotional symptoms differ from underlying neuropathic pain mechanisms. Irina Strigo discusses emotional allodynia and neural systems reinforcing negative emotional state associated with pain unpleasantness in depression and compare to trauma and anxiety disorders. Evidence from studies using qualitative sensory testing and functional MRI on pain expectation and processing support a neural model for overlap between pain and psychopathology seen clinically. Walter Magerl will show that depressive patients exhibit normal somatosensory profiles. However, when challenged their nociceptive system shifts towards descending pain facilitation, precipitates stronger pain amplification (modulated by SNRIs) and displays a lack of pain-related upward-tuning of prefrontal brain areas.


11:00pm EST

Impact of Psychiatric Co-Morbidities on Anticipation and Processing of Experimental Pain

Tracks: Mechanisms
Categories: Topical Workshop
Presented By: Irina Strigo

Pain is often co-morbid with depression, trauma, and anxiety. Understanding how aspects of the multidimensional pain experience are altered by the co-morbid symptoms is important for the development of effective therapeutic interventions.

We conducted behavioral and neuroimaging experiments in individuals with major depression, posttraumatic stress, traumatic brain injury, and chronic pain. Several aspects of pain anticipation and processing were altered in individuals with psychopathology compared to those without. We found that individuals with major depression experience emotional allodynia, or a subjectively enhanced perception of unpleasantness in response to temperature stimuli that are not normally perceived as unpleasant. Consistent with this behavioral manifestation, we found changes in insula response during anticipation of pain and emotional allodynia. Conversely, our studies in post-traumatic stress and traumatic brain injury show disruption within pain-modulatory network connectivity, while individuals with chronic pain show abnormal brain response to pain relief anticipation. Furthermore, we found brain phenotypes of altered response and connectivity in individuals with co-morbid chronic pain and psychopathology. Results will be discussed in relation to treatment development and personalized medicine.

11:00pm EST

Modeling Emotional Pain in an Animal Model of Neuropathic Pain

Tracks: Mechanisms
Categories: Topical Workshop

Often, the focus in animal models of chronic pain is on the experience of pain. However, in humans, co-morbidity with depressive symptoms is highly common. We modelled this in rats using the sciatic nerve ligation (SNL) model of chronic neuropathic pain. The level of neuropathic pain was assessment by von Frey hairs and demonstrated clear mechanical allodynia. We tested a battery of behavioral tests to examine comorbid emotional symptoms, which identified large individual variability, with some animals presenting only symptoms of mechanical allodynia (emotionally-unaffected), but others exhibiting also comorbid emotional symptoms (emotionally-affected). Both groups displayed similar levels of mechanical allodynia. Preventing the degradation of endogenous cannabinoids by inhibiting fatty acid amide hydrolase (FAAH) did not reduce mechanical allodynia, but significantly reduced emotional symptoms exclusively in emotionally-affected individuals.
In aggregate, this shows that the mechanisms involved in the emotional symptoms differ from underlying neuropathic pain per se. Enhancing endocannabinoid modulation may be beneficial for the emotional symptoms co-morbidity, even if not reducing the chronic pain per se. This could already contribute significantly to the well-being of patients suffering from chronic pain.

11:00pm EST

Novel Synaptic Mechanisms for Chronic Pain and Anxiety

Tracks: Mechanisms
Categories: Topical Workshop
Presented By: Prof. Min Zhuo

Glutamate is the primary excitatory transmitter of sensory transmission and perception in the central nervous system. Painful or noxious stimuli 'teach' humans and animals to avoid potentially dangerous objects or environments, whereas tissue injury itself causes unnecessary chronic pain that can even last for long periods of time.  Conventional pain medicines often fail to control chronic pain.  Recent neurobiological studies suggest that synaptic plasticity taking place in sensory pathways, from spinal dorsal horn to cortical areas, contributes to chronic pain.  We have characterized two forms of long-term potentiation (LTP) in the anterior cingulate cortex (ACC); a presynaptic form (pre-LTP) that requires kainate receptors and a postsynaptic form (post-LTP) that requires N-methyl-D-aspartate receptors. Our results demonstrate that cortical LTPs contribute to chronic pain and anxiety; and inhibiting these different forms of LTP may help us to develop novel drugs for the future treatment of chronic pain and anxiety.

11:00pm EST

Dysregulated Pain Processing and Pain Plasticity in Patients with Major Depressive Disorder

Tracks: Mechanisms
Categories: Topical Workshop
Presented By: Mr. Walter Magerl

We studied pain processing in patients with major depressive disorder (MDD) on several levels to understand whether the depressive condition amplifies pain experience and/or pain plasticity. Quantitative sensory testing revealed that MDD patients exhibited only liminal differences of their somatosensory pattern compared to healthy subjects. In contrast, when challenged by two different experimental models of hyperalgesia human pain-LTP or sustained painful heat exposure) MDD patients responded with similar heat hyperalgesia, but significantly enhanced secondary hyperalgesia and allodynia pointing towards increased central sensitization, which correlated to their degree of anxiety and depression. Importantly, SNRIs mitigated the hyperalgesia dose-dependently to a very relevant degree.
Moreover, as tested by conditioning pain modulation, descending pain control shifted significantly towards facilitation in MDD patients. Imaging experiments revealed significantly lower functional connectivity and a complete absence of adaptive engagement of prefrontal cortical areas during the hyperalgesia-inducing sustained heat stimulation. Collectively, the data support the interpretation that MDD patients are prone to respond with exaggerated pain amplification related to an imbalance of their inhibitory vs. facilitatory descending pain control, which may be related to their deficit of prefrontal pain control.


Professor Gal Richter-Levin

Head, Laboratory for Behavioral Neuroscience
University of Haifa

Irina Strigo

Research Biologist/Professor

Prof. Min Zhuo

Temerty Faculty of Medicine

Mr. Walter Magerl

Deputy Head of Department
Medical Faculty Mannheim, Heidelberg University