Ugo Basile

Search the blog


Quote list0
Your product list is empty!

Thermal Gradient Ring: bias-free, automated pain and thermal preference in mice

Three cute white mice

Thermal Gradient Ring: bias-free, automated pain and thermal preference in mice

The Thermal Gradient Ring (TGR) by Ugo Basile represents a significant leap forward in studying thermal nociception, and temperature preference, offering researchers a powerful tool for unraveling the complexities of temperature preference regulation, pain and inflammation.

Learn more on our new version of Thermal Gradient Ring:

The genesis of the Thermal Gradient Ring can be traced back to the pioneering work of Dr. Katharina Zimmermann, whose groundbreaking research focused on thermal nociception and has been introduced with the paper "Comprehensive thermal preference phenotyping in mice using a novel automated circular gradient assay" (Temperature, 2016, Touska, F. et al.). This assay utilizes the Thermal Gradient Ring (TGR), which provides temperature gradient within a circular track. Mice can move freely within this gradient, allowing researchers to observe their temperature preferences without human interference. The TGR enhances accuracy and minimizes biases found in traditional methods, making it an essential tool for studying the thermal sensitivity of genetically modified mice, particularly those with alterations in TRP channels​.

Recognizing the potential of this approach, Ugo Basile has collaborated with Dr. Zimmermann to develop an advanced device that would streamline the process and enhance research capabilities.

Use and Applications of the Thermal Gradient Ring

The Thermal Gradient Ring is designed to facilitate the study of temperature preference and thermal nociception in rodents, offering researchers a versatile tool for investigating sensitivity, pain and inflammation mechanisms. By applying a controlled temperature gradient to the floor the animal walks on, the TGR enables precise manipulation of thermal stimuli, allowing researchers to assess thermal sensitivity, nociceptive thresholds and the efficacy of analgesic compounds.

The TGR has been used to study sensory neuropathies (2020, Valek et al.), diabetic peripheral neuropathy with symptoms of the thermosensory impairment (2022, Sasajima et al.), TRP channels (2022, Ujisawa et al.) and CCI-induced thermal hyperalgesia. The TGR records and analyses thermal preference phenotyping in mice. For neuropathic pain studies, peripheral neuropathy, temperature sensitivity and insensitivity assessment in basic research, phenotyping and drug screening.

In fact, one of the key applications of the TGR is in preclinical drug discovery, where researchers can evaluate the efficacy of potential pain-relieving compounds in a controlled laboratory setting. By measuring behavioral responses to thermal stimuli, researchers can assess the analgesic effects of different compounds, providing valuable insights into their potential clinical utility.

In the TGR, mice can freely move around the ring, thereby avoiding the stereotypical habit that mice have of staying in a corner, as occurs in rectangular systems. An infrared camera is located on the upper side of the apparatus, together with a visible and infrared illuminator and an infrared transmissive inner wall.

The position of the freely moving animal is tracked by the camera, and no user intervention is required to gather time spent in each temperature zone (12 zones in duplicate) and many other parameters.

The behavioral data is obtained by video-tracking with ANY-Maze software and automatically generates measurement parameters, such as:

  • Thermal zone occupancy: percentage of time spent in a zone.
  • Zone entries: number of entries in each zone.
  • Preference temperature: calculated as the weighted preferred temperature.
  • Cumulative distance: calculation of the cumulative distance per zone or per the whole apparatus.
  • Zone occupancy
  • Time spent above preferred temperature
  • Coordinates of location within the Ring: can be used to visualize mouse behaviour in the ring with Heat Maps.
  • Many other parameters typical of video-tracking

Key features of the Thermal Gradient Ring include:

  • Circular Design: the ring-shaped enclosure provides a continuous and seamless environment for animals to navigate, ensuring uninterrupted observations of their thermal preferences.
  • Broad temperature range: temperature can be set from 4 to 65°C
  • Heater and cooler units on opposite sides: symmetric thermal gradient, superior to two-plate choice design.
  • CCD-IR camera and ANY-maze video-tracking software: behavior of the animal recorded automatically during test time
  • Designed for tethered and non-tethered animals: for optogenetic, electrophysiology and other tethered animal studies
  • Thermal sensor embedded in the Thermal Gradient Ring sensing the temperature: the exact temperature gradient measured in real time
  • Control ambient temperature: improve temperature accuracy avoiding laboratory temperature oscillations

TGR 2.0: New design for tethered and non-tethered animals.

Recently, Ugo Basile has developed a new version of the TGR, introducing several important innovations.

The main novelty is the possibility to conduct experiments on tethered animals. This is made possible by the new design which includes an adjustable swivel holder, that support most of the available swivels on the market, and guidance for the animal cable, which is easy set-up change for tethered and non-tethered mice.

Moreover, the new TGR is available with two different heights of the maze walls which are now even easier and faster to remove for cleaning procedures, a needed action when changing animal for a new test.

Learn more on our new version of Thermal Gradient Ring:

Scientific Insights Enabled by the Thermal Gradient Ring

The Thermal Gradient Ring has played a crucial role in numerous scientific studies, advancing our understanding of temperature-dependent behaviors and their underlying mechanisms. Several notable research papers have utilized the TGR to investigate various aspects of thermosensation and sensory neuropathies in mice:

Exploring Thermosensitive Ion Channels

TGR Paper TGR Exploring Thermosensitive Ion Channels

The Thermal Gradient Ring has played a key role in elucidating the functions of thermosensitive ion channels, such as TRP channels, in temperature perception. In the study "Thermal gradient ring for analysis of temperature-dependent behaviors involving TRP channels in mice" (The Journal of Physiological Sciences, 2024, Ujisawa, T. et al. (Prof. Tominaga Lab)), researchers utilized the TGR to explore the involvement of TRP channels in temperature-dependent behaviors in mice, being their role in these behaviors not fully understood. By employing the TGR the scientists achieved to overcome the limitations of previous methods, like the lack of temperature resolution of two-temperature choice systems or linear thermal gradient devices which do not exclude the possibility for the mouse to remain in a corner. In the TGR, the temperature resolution and range can be adjusted and the mouse can move freely in a circle. Additionally, thanks to a video-tracking system, the TGR automatically delivers results on the time spent on each of the twelve temperature zones, the preferred temperature and several other automated parameters to describe animal temperature behavior. The study emphasizes the importance of analyzing multiple parameters like travel distance and moving speed alongside spent time to fully understand temperature-dependent behaviors.

Thermal Sensation in Mice, TRPV3 and TMEM79 Insights

TGR Paper TRPV3 and TMEM79 Insights

The paper "Involvement of skin TRPV3 in temperature detection regulated by TMEM79 in mice" (Nature Communications, 2023, Lei, J. et al. (Prof. Tominaga Lab)) explores the molecular mechanisms underlying temperature sensation in mice, focusing on the TRPV3 channel and its regulation by TMEM79. TMEM79 interacts with TRPV3, a temperature-sensitive ion channel, modulating its activity and influencing temperature detection. Mice lacking TRPV3 showed altered responses to warmth, highlighting its role in thermal sensation. TMEM79 regulates TRPV3 activity; mice deficient in TMEM79 had similar thermal detection deficits as those lacking TRPV3, emphasizing TMEM79's importance. Biochemical analyses revealed TMEM79 enhances TRPV3 stability and function, essential for normal thermal response. Behavioral experiments using thermal gradient assays confirmed that mice lacking either TRPV3 or TMEM79 had impaired thermal preference, underscoring the TRPV3-TMEM79 interaction's significance. The Ugo Basile Thermal Gradient Ring (TGR) was crucial in these discoveries, providing a controlled environment to assess mice's temperature preferences. The TGR demonstrated specific thermal deficits in genetically modified mice, allowing researchers to quantify the impact of genetic modifications on thermal sensation. These findings offer valuable insights into the molecular mechanisms of thermal sensation and potential targets for sensory dysfunctions..

Unveiling Diabetic Neuropathy

TGR Paper Unveiling Diabetic Neuropathy

The paper "Thermal gradient ring reveals thermosensory changes in diabetic peripheral neuropathy in mice" (Scientific Reports, 2022, Sasajima, S. et al.) analysis the application of the Thermal Gradient Ring (TGR) to investigate thermosensory alterations in diabetic peripheral neuropathy (DPN) in mice. Leveraging this innovative tool, researchers made groundbreaking discoveries regarding the effects of diabetes on thermosensation. DPN includes symptoms of thermosensory impairment, which are reported to involve changes in the expression or function, or both, of nociceptive TRPV1 and TRPA1 channels in rodents. In the study, changes in the expression or function of TRPV1 or TRPA1 in DPN mice caused by Streptozotocin, commonly used to create a model of type 1 DM in rodents, were not find, although thermal hypoalgesia was observed in a murine model of DPN or TRPV1−/− mice with a Plantar test, which specifically detects temperature avoidance. With a Thermal Gradient Ring in which mice can move freely in a temperature gradient, temperature preference can be analyzed, and the temperature‑dependent phenotype between DPN and TRPV1−/− mice can be clearly discriminated.

Early Sensory Neuropathy in Parkinson’s

TGR Paper Early Sensory Neuropathy in Parkinson

The use of the Thermal Gradient Ring was instrumental in highlighting the critical role of glucosylceramides in sensory neuropathy in a Parkinson's disease (PD) mouse model by identifying specific thermal sensitivity deficits. The paper "Prodromal sensory neuropathy in Pink1−/−SNCAA53T double mutant Parkinson mice" (Neuropathology and Applied Neurobiology, 2021, Valek, L. et al.) investigates the early sensory neuropathy observed in PD and its association with glucosylceramide accumulation. The study utilized Pink1−/−SNCAA53T double mutant mice, which model PD, to examine the underlying mechanisms of sensory neuropathy that precedes the motor symptoms of the disease. The TGR behaviour suggested paradoxical heat sensation and loss of cold sensation, which was confirmed for trigeminal hot/cold stimulation in the Orofacial Pain Assessment Device. Pink1−/−SNCAA53T showed a preference for unpleasant cold temperatures when compared to wild-type mice. The TGR's ability to track and analyze the thermal preference behaviors of the mice was essential in demonstrating the early onset of sensory neuropathy and its progression, thereby validating the mouse model as a reliable proxy for human PD-associated sensory issues.

Uncovering Mouse Thermal Preferences

TGR Paper MethodThe paper "Comprehensive thermal preference phenotyping in mice using a novel automated circular gradient assay" (Temperature, 2016, Touska, F. et al.) introduced for the very first time the Thermal Gradient Ring (TGR), a pioneering tool for studying thermal preference in mice. This automated circular gradient assay enables precise measurement of thermal preferences in mice, offering valuable insights into their behavior. Through meticulous experimentation, the researchers uncovered several significant discoveries. Firstly, they observed that mice exhibit distinct temperature preferences based on factors such as strain, sex, and circadian rhythm. Additionally, the TGR facilitated the identification of thermosensitive phenotypes in genetically modified mice, shedding light on the underlying mechanisms of thermal regulation. Moreover, the researchers demonstrated the efficacy of the TGR in detecting subtle changes in thermal preference associated with various physiological and pathological conditions, thereby highlighting its potential for studying thermoregulatory disorders. Overall, this paper underscores the importance of the TGR in advancing our understanding of thermal preference phenotypes in mice and its implications for biomedical research.

Still need more info on the NEW version of Thermal Gradient Ring? Contact our Sales Departement!