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Department of Pharmacology

 
Read more at: The Somatosensory World of the African Naked Mole-Rat.

The Somatosensory World of the African Naked Mole-Rat.

The naked mole-rat (Heterocephalus glaber) is famous for its longevity and unusual physiology. This eusocial species that lives in highly ordered and hierarchical colonies with a single breeding queen, also discovered secrets enabling somewhat pain-free living around 20 million years ago. Unlike most mammals, naked mole-rats do not feel the burn of chili pepper's active ingredient, capsaicin, nor the sting of acid.


Read more at: The naked truth: a comprehensive clarification and classification of current ‘myths’ in naked mole-rat biology

The naked truth: a comprehensive clarification and classification of current ‘myths’ in naked mole-rat biology

The naked mole-rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g. tolerance of variable oxygen availability), which may be pertinent to several human disease states, including ischemia/reperfusion injury and neurodegeneration.


Read more at: Cell-cell interactions in joint pain: rheumatoid arthritis and osteoarthritis

Cell-cell interactions in joint pain: rheumatoid arthritis and osteoarthritis

Rheumatoid and osteoarthritis are chronic conditions generating joint pain for which better management is required. We argue that a better understanding of the cell-to-cell interactions occurring within the joint will enhance mechanistic understanding of joint pain and could lead to new therapeutic avenues being explored.


Read more at: Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage in vitro.

Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage in vitro.

Naked mole-rats are extraordinarily long-lived rodents that offer unique opportunities to study the molecular origins of age-related neurodegenerative diseases. Remarkably, they do not accumulate amyloid plaques, even though their brains contain high concentrations of amyloid beta (Aβ) peptide from a young age. Therefore, they represent a particularly favourable organism to study the mechanisms of resistance against Aβ neurotoxicity. Here we examine the composition, phase behaviour, and Aβ interactions of naked mole-rat brain lipids.


Read more at: Acid-Sensing Ion Channel 3: An Analgesic Target

Acid-Sensing Ion Channel 3: An Analgesic Target

Acid-sensing ion channel 3 (ASIC3) belongs to the epithelial sodium channel/degenerin (ENaC/DEG) superfamily. It consists of one of 7 different ASIC subunits encoded by 5 different genes. Most ASIC subunits form trimeric ion channels that upon activation by extracellular protons mediate a transient inward current inducing cellular excitability. ASIC subunits exhibit differential tissue expression and biophysical properties, and the ability of subunits to form homo- and heteromeric trimers further increases the complexity of currents measured and their pharmacological properties.


Read more at: Photoacoustics resolves species-specific differences in haemoglobin concentration and oxygenation

Photoacoustics resolves species-specific differences in haemoglobin concentration and oxygenation

Significance: Photoacoustic imaging (PAI) enables the detection of blood haemoglobin (HB) concentration and oxygenation (sO2) with high contrast and resolution. Despite the heavy use of photoacoustic total haemoglobin (THbMSOT) and sO2 biomarkers in PAI research, their relationship with underlying biochemical blood parameters and the impact of intra- and inter-species genetic variability have yet to be established.
Aim: To explore the relationship between THbMSOT and sO2 photoacoustic biomarkers and the underlying biochemical blood parameters in a species-specific manner.


Read more at: Peripheral mechanisms of arthritic pain: A proposal to leverage large animals for in vitro studies.

Peripheral mechanisms of arthritic pain: A proposal to leverage large animals for in vitro studies.

Pain arising from musculoskeletal disorders such as arthritis is one of the leading causes of disability. Whereas the past 20-years has seen an increase in targeted therapies for rheumatoid arthritis (RA), other arthritis conditions, especially osteoarthritis, remain poorly treated. Although modulation of central pain pathways occurs in chronic arthritis, multiple lines of evidence indicate that peripherally driven pain is important in arthritic pain. To understand the peripheral mechanisms of arthritic pain, various in vitro and in vivo models have been developed, largely in rodents.


Read more at: Transformation of naked mole-rat cells.

Transformation of naked mole-rat cells.


Read more at: Neurobiology: Crowdsourcing CO2 to Conserve Brain Energy.

Neurobiology: Crowdsourcing CO2 to Conserve Brain Energy.

Naked mole-rats are adapted to living in a low-oxygen and high-CO2 environment. Elevated environmental CO2 inhibits brain activity and has acted as a selection pressure to reduce GABAergic tone, which in turn reduces energetic needs in a hypoxic habitat.


Read more at: Human labour pain is influenced by the voltage-gated potassium channel Kv6.4 subunit

Human labour pain is influenced by the voltage-gated potassium channel Kv6.4 subunit

By studying healthy women who do not request analgesia during their first delivery we investigate genetic effects on labour pain. Such women have normal sensory and psychometric test results, except for significantly higher cuff-pressure pain. We find an excess of heterozygotes carrying the rare allele of SNP rs140124801 in KCNG4. The rare variant KV6.4-Met419 exerts a dominant negative effect and cannot modulate the voltage-dependence of KV2.1 inactivation because it fails to traffic to the plasma membrane.