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Thermosensation01:43

Thermosensation

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Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...
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Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
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Major Somatic Sensory Pathways01:28

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Sensory impulses related to touch, pressure, vibration, and proprioception from various body parts, such as the limbs, trunk, neck, and posterior head, travel to the cerebral cortex through the posterior column-medial lemniscus pathway. The pathway’s name derives from the two white-matter tracts that convey the impulses: the spinal cord's posterior column and the brainstem's medial lemniscus. First-order sensory neurons extend their axons into the spinal cord, forming the...
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Nociception01:44

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Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain.
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Sensory Functions of the Skin01:16

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The skin is the largest organ of the human body and plays a crucial role in our sensory perception. It contains a vast network of sensory receptors that contribute to the skin's protective function by perceiving physical, biological, and environmental cues and generating relevant responses.
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Somatic sensory or somatosensory pathways refer to the neural pathways that carry information related to touch, pressure, pain, temperature, and proprioception from the skin, muscles, tendons, and joints to the brain. These pathways involve several stages of processing and integration of sensory information.
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Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4
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To not be hot when TRPV1 is not.

Peter M Blumberg1

  • 1Laboratory of Cancer Biology and Genetics; Center for Cancer Research; National Cancer Institute ; Bethesda, MD, USA.

Temperature (Austin, Tex.)
|May 27, 2016
PubMed
Summary

Developing new TRPV1 antagonists to manage pain is challenging due to hyperthermia side effects. Researchers are exploring complex TRPV1 pharmacology to create safer, effective pain relief medications.

Keywords:
TRPV1TRPV1, transient receptor potential vanilloid-1antagonistcapsaicindrug developmentpainthermoregulationvanilloid

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Area of Science:

  • Pharmacology
  • Neuroscience
  • Pain Management

Background:

  • Transient Receptor Potential Vanilloid-1 (TRPV1) nociceptors play a key role in pain signaling.
  • Hyperthermia is a significant side effect limiting the therapeutic development of TRPV1 antagonists.
  • Understanding TRPV1 pharmacology is crucial for developing targeted pain therapies.

Purpose of the Study:

  • To investigate novel ligands that avoid hyperthermia associated with TRPV1 antagonism.
  • To explore the mechanistic basis of TRPV1 ligand action on thermoregulation.
  • To advance the development of safer and more effective TRPV1-based therapeutics.

Main Methods:

  • Exploiting complex TRPV1 pharmacology to design new ligands.
  • Investigating the effects of novel ligands on TRPV1 activity.
  • Analyzing the impact of TRPV1 ligands on physiological thermoregulation.

Main Results:

  • Identification of new TRPV1 ligands with reduced hyperthermic potential.
  • Gained insights into the mechanisms by which TRPV1 ligands influence body temperature.
  • Demonstrated a potential pathway to dissociate analgesic effects from hyperthermia.

Conclusions:

  • Novel strategies targeting TRPV1 pharmacology can mitigate hyperthermia side effects.
  • Further research into TRPV1 mechanisms will facilitate the development of improved pain therapeutics.
  • The findings pave the way for developing safer antagonists for chronic pain management.