Nov 18, 2021

The role of alternative splicing in controlling non-ionotropic signalling of N-methyl-D-aspartate receptors of the central nervous system

N-methyl-D-aspartate receptors (NMDARs) are receptors in the central nervous system (CNS) known for their role in disease, plasticity and neuronal development. They are made up of two glycine-binding GluN1 subunits and two glutamate-binding GluN2 subunits. Typically, NMDARs signal ionotropically (with ion influx), however increasing evidence suggests that these receptors also signal non-ionotropically, or metabotropically. This occurs through glycine binding on the GluN1 subunits, but the molecular control of non-ionotropic signaling in NMDARs remains unknown. The GluN1 subunit comprises of eight alternatively spliced isoforms produced by the inclusion or exclusion of N1 and the C1, C2, C2’ polypeptide cassettes. Given the diversity that exists in GluN1 isoforms within the CNS and the role that differential splicing has on hippocampal long-term potentiation, UTCSP scientist Dr. Michael Salter and colleagues investigated whether alternative splicing of GluN1 would affect non-ionotropic signaling of NMDARs on hippocampal neurons. To do this, they examined glycine-induced signaling with all eight splice isoforms of GluN1 with heterologously expressed NMDARs in mice; representative isoforms in mice engineered to express only GluN1a (lacking N1 cassette) or GluN1b (containing N1 cassette) variants, and wild-type mice (WT).
Oct 14, 2021

Baseline functional connectivity of key nodes in pain processing and modulation determine subsequent pain ratings of an ecologically valid model of orofacial pain

Neuroimaging studies have identified that individual differences in pain sensitivity are related to structural gray matter differences and functional connectivity between brain regions involved in pain processing. However, experimental pain models in these laboratory studies are limited in ecological validity, as they do not mimic the persistent pain that typically occurs in real-life experiences. UTCSP members Dr. Iacopo Cioffi and Dr. Massieh Moayedi and colleagues investigated whether baseline structure and function of key brain regions involved in ascending and descending pain pathways correlate with subsequent peak pain intensity ratings induced by an ecologically and clinically relevant orofacial pain model.
Sep 15, 2021

Sex Specific Subgenual Anterior Cingulate Cortex Abnormalities in Chronic Pain Conditions Prevalent in the Opposite Sex

The subgenual anterior cingulate cortex (sgACC) is known for its importance within the descending pain modulation (DPM) pathway, through its interconnectivity with other key parts of the DPM pathway and role in endogenous opioidergic pain inhibition. Previous work using fMRI and MEG in the Davis Lab has shown abnormalities within the sgACC across different chronic pain conditions. More specifically, it has been demonstrated that the sgACC has abnormal functional connectivity (FC) in women but not men, in a male prevalent chronic pain condition (Ankylosing Spondylitis). Carpel Tunnel Syndrome (CTS) is a neuropathic pain condition characterized by pain, numbness and tingling in the hands, due to damage caused by compression of the median nerve of the wrist. To complement their work observing sgACC FC in a male dominant chronic pain condition, the aim of this study was to characterize sgACC activity in CTS, which is a female prevalent chronic pain condition. The goal was to observe whether abnormal sgACC FC is characteristic of women with chronic pain or found in individuals that have a chronic pain condition that is more prevalent in the opposite sex.
Aug 26, 2021

2021/22 UTCSP Pain Scientist Scholarship Awardees

Congratulations to the following students who received the 2021/22 UTCSP Pain Scientist Scholarship:

Prabjit Ajawat (Hance Clarke lab)
Laura Bennett (Rob Bonin lab)
Rima El-Sayed (Karen Davis lab)
Sandra Poulson (Loren Martin lab)

Click HERE to view awardee bios/photos
Aug 18, 2021

Pain relief from trigeminal neuralgia reverses hippocampal abnormalities

Memory and concentration difficulties are some of the frequently reported difficulties that chronic pain patients face. Recent evidence points to the hippocampus as the affected region in chronic pain that may result in these symptoms, as the hippocampus is involved in memory consolidation, behaviour regulation, and stress modulation.
Jul 12, 2021

The role of rostral ventromedial medulla ON and OFF cells in nociceptive behaviour in multiple body regions

The rostral ventromedial medulla (RVM) is known to play a role in the endogenous modulation of nociceptive transmission in the central nervous system (CNS), within both spinal cord and trigeminal nociceptive pathways. It is thought that descending controls that are exerted by the RVM have a modulatory effect on pain sensations. In rats, neurons in the RVM have been classified as ON-cells, OFF-cells or NEUTRAL cells based on whether they elicit a tail flick response, with ON cells facilitating and OFF-cells inhibiting this nociceptive response. There has been evidence that has also shown that ON and OFF cell activity facilitate the activity of spinal dorsal horn (SDH) and medullary dorsal horn (MDH) neurons, and thereby underlie a potential important role of the RVM in endogenous pain control. However, the contribution and neural activity patterns of ON and OFF cells in relation to craniofacial nociceptive behaviours has not been explored in-depth.  In this study, UTCSP scientists Dr. Barry Sessle, Dr. Jonathon Dostrovsky and colleagues aimed to uncover whether RVM neuronal activity is related to noxious heat-induced craniofacial nociceptive behaviour, specifically jaw motor response, and compare it to other regions such as the tail.
Jun 7, 2021

A novel role for T-type calcium channels in the spinal cord in pain processing

T-type channels have been implicated in pain processing in numerous previous studies using rodent models of chronic pain. T-type calcium channels are low voltage-activated calcium channels, contributing to subthreshold excitability of neurons. These channels are upregulated in peripheral sensory neurons during chronic pain. However, recent studies found that administration of T-type channel antagonists that are peripherally-restricted were ineffective in reversing pain hypersensitivity.


Queen Elizabeth II/Study of Pain Graduate Scholarship in Science and Technology (QEII-GSST)

Applications for the Temerty Faculty of Medicine QEII-GSST is now available.  The QEII-GSST program is designed to encourage excellence in graduate studies in science and technology.
Application Deadline:  April 8, 2022
Click HERE for complete competition details

IASP's Global Year About Back Pain

January marked the launch of IASP's 2021 Global Year About Back Pain. IASP sponsors and promotes the Global Year For Pain, which is a year-long initiative designed to raise awareness of various aspects of pain. This year's theme focuses on helping clinicians, scientists, those living with pain, and the public understand the nature of back pain and the utility of available treatment modalities.

For further information, please visit the IASP website

Pain in the News

Nov 20, 2021

Cortical mechanisms in migraine

Molecular Pain, Volume 17, Issue , January-December 2021.
Migraine is the second most prevalent disorder in the world; yet, its underlying mechanisms are still poorly understood.
Nov 10, 2021

Selective inhibition of adenylyl cyclase subtype 1 reduces inflammatory pain in chicken of gouty arthritis

Molecular Pain, Volume 17, Issue , January-December 2021.
Lack of uricase leads to the high incidence of gout in humans and poultry, which is different from rodents.
Oct 18, 2021

A systematic review on descending serotonergic projections and modulation of spinal nociception in chronic neuropathic pain and after spinal cord stimulation

Molecular Pain, Volume 17, Issue , January-December 2021.
Chronic neuropathic pain is a debilitating ordeal for patients worldwide and pharmacological treatment efficacy is still limited.
Sep 13, 2021

Interferon-β suppresses inflammatory pain through activating µ-opioid receptor

Molecular Pain, Volume 17, Issue , January-December 2021.
Interferons (IFNs) are cytokines secreted by infected cells that can interfere with viral replication.
Sep 9, 2021

Tetrahydropalmatine exerts analgesic effects by promoting apoptosis and inhibiting the activation of glial cells in rats with inflammatory pain

Molecular Pain, Volume 17, Issue , January-December 2021.
BackgroundPain is an unpleasant sensory experience that usually plays a protective role.
Sep 9, 2021

Reduced concentrations of vaginal metabolites involved in steroid hormone biosynthesis are associated with increased vulvar vestibular pain and vaginal muscle tenderness in provoked vestibulodynia: An exploratory metabolomics study

Molecular Pain, Volume 17, Issue , January-December 2021.
Provoked vestibulodynia (PVD) is a chronic vulvar pain disorder characterized by hypersensitivity and severe pain with pressure localized to the vulvar vestibule.