Old and novel mechanisms for nociception involving TRPV1 are shown. Credit: National Institute for Physiological Sciences
Drs. Takayama and Tominaga in National Institute for Physiological Sciences (NIPS) (Okazaki Institute for Integrative Bioscience) clarified that an interaction between capsaicin receptor TRPV1 and chloride channel anoctamin 1 causes enhancement of the capsaicin-evoked pain sensation in mice in collaboration with Dr. Uta (Toyama University) and Dr. Furue (NIPS). This result will be published in the Proceedings of the National Academy of Sciences of the United States of America.
It has been well known for more than 10 years that capsaicin contained in capsicums causes pungent (pain) sensation through activation of capsaicin receptor TRPV1 expressed in sensory neurons. Anoctamin 1 is also known to be involved in nociception independent of TRPV1. Drs. Takayama and Tominaga found that nociceptive responses are increased by anoctamin 1 activated by TRPV1 which binds to anoctamin 1 in the analyses using sensory neurons and spinal cord of mice. In addition, they proved that chemical blockade of anoctamin 1 is effective for relief of pain induced by TRPV1 activation.
The research group focused on the two ion channel proteins, TRPV1 and anoctamin 1 in mouse sensory neurons. And, they found that anoctamin 1 activation is accompanied by TRPV1 activity and that this sequential channel activation enhances capsaicin-evoked pain sensation.
Capsaicin-evoked burning pain sensation is induced by neural excitation through activation of TRPV1 in sensory neurons. While hot water activates TRPV1, capsaicin is stronger stimulus for TRPV1. Because TRPV1 is a non-selective cation channel, people believed that Na+ ion influx through TRPV1 pore causes depolarization, leading to the action potential generation (Figure 1, left). In this study, however, the research found a novel pain-enhancing mechanism in which anotamin 1 activated by Ca2+ ions entering cells through TRPV1 causes chloride efflux because intracellular chloride concentrations are high in the sensory neurons, which leads to further depolarization. In addition, the research group found that the functional interaction is based on their physical binding, indicating that Ca2+ ions work in the nanodomain within 20 nm distance (Figure 1, right). Furthermore, the research group observed that pain-related licking behaviors in mouse hind paws given capsaicin were inhibited by an anoctamin 1 blocker (Figure 2). Protein produced in the sensory neuron cell bodies are believed to be transferred not only to the peripheral sensory nerve endings, but also to the presynaptic terminals of the primary afferent neurons. Nociceptive signal transmission from primary afferent neurons to the second neurons in spinal cord was also reduced by anoctamin 1 blockade. Thus, anoctamin 1 blockade is useful to reduce the TRPV1-mediated pain responses.
Anoctamin1 blockade inhibits capsaicin-evoked pain-related behaviors. Credit: National Institute for Physiological Sciences
An old mechanisms (left): 1) capsaicn activates TRPV1, 2) Na+ ions enter sensory neurons through the TRPV1 pore, 3) action potentials are generated (neurons are excited). A novel mechanism (right): capsaicn activates TRPV1, 2) Ca2+ ions enter sensory neurons through the TRPV1 pore, 3) because intracellular chloride concentrations are high in the sensory neurons, chloride ion efflux is induced by anoctamin 1 activated by Ca2+ ions within 20 nm distance from TRPV1 through physical binding of the two proteins, 4) action potentials are generated. Thus, capsaicin-induced inward currents are composed of two components: TRPV1-mediated Na+ influx and anon efflux through anotamin 1 activated by Ca2+ ions entering cells through TRPV1.
Nociceptive information transmission upon capsaicin application was in inhibited by an anoctamin 1 blocker. Credit: National Institute for Physiological Sciences
Mice keep licking their hind paws upon capsaicin injection. Time spent for licking for 5 min was reduced by concomitant application of an anoctamin1 blocker.
Nociceptive signals are transmitted from the primary afferent neurons to the second neurons in spinal cord with a neurotransmitter glutamate. The electric signals can be observed (a red arrow). Capsaicin increases such electric signals. However, the increase was reduced by an anoctamin 1 blocker.
Explore further: Pepper and halt: Spicy chemical may inhibit gut tumors
More information: Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in sensory neurons, PNAS, http://ift.tt/1F7m6Ye
Journal reference: Proceedings of the National Academy of Sciences
Provided by National Institutes of Natural Sciences
Medical Xpress on facebook
Related Stories
Pepper and halt: Spicy chemical may inhibit gut tumors
Researchers at the University of California, San Diego School of Medicine report that dietary capsaicin – the active ingredient in chili peppers – produces chronic activation of a receptor on cells lining ...
Too hot to handle! Scientists identify heat sensing regulator
Neuroscientists at Johns Hopkins are a step closer to understanding pain sensitivity - specifically why it’s variable instead of constant - having identified a gene that regulates a heat-activated molecular sensor. Their ...
Putting the fire out with light
Chili peppers contain an activator of heat-sensitive pain receptors. An LMU team has now converted an antagonist to the compound into a light-sensitive regulator of such receptors that can differentially ...
Scientists discover pain receptor on T-cells
Researchers at University of California, San Diego School of Medicine have discovered that T-cells – a type of white blood cell that learns to recognize and attack microbial pathogens – are activated by a pain receptor.
Blocking pain receptors found to extend lifespan in mammals
Blocking a pain receptor in mice not only extends their lifespan, it also gives them a more youthful metabolism, including an improved insulin response that allows them to deal better with high blood sugar.
Recommended for you
Near-death brain signaling accelerates demise of the heart
What happens in the moments just before death is widely believed to be a slowdown of the body's systems as the heart stops beating and blood flow ends.
Multiple sclerosis patients could benefit from brain boost
Multiple sclerosis patients could one day benefit from treatments that boost their brain function, a study suggests.
Study provides new insight into what occurs in the brain during the learning process
Why are some people able to master a new skill quickly while others require extra time or practice? That was the question posed by UC Santa Barbara's Scott Grafton and colleagues at the University of Pennsylvania ...
Neurologic function, temperature management in patients after cardiac arrest
Quality of life was good and cognitive function was similar in patients with cardiac arrest who received targeted body-temperature management as a neuroprotective measure in intensive care units in Europe and Australia, according ...
Toward a model of synchrony in brain networks
(MedicalXpress)—Resting state networks (RSNs) in the brain are topographies of neural structures between which lag states propagate due to fluctuations of physical and other activities. Studying these networks ...
Deconstructing brain systems involved in memory and spatial skills
In work that reconciles two competing views of brain structures involved in memory and spatial perception, researchers at University of California, San Diego School of Medicine have conducted experiments ...
User comments
Please sign in to add a comment. Registration is free, and takes less than a minute. Read more
Click here to reset your password.
Sign in to get notified via email when new comments are made.
Old and novel mechanisms for nociception involving TRPV1 are shown. Credit: National Institute for Physiological Sciences
Drs. Takayama and Tominaga in National Institute for Physiological Sciences (NIPS) (Okazaki Institute for Integrative Bioscience) clarified that an interaction between capsaicin receptor TRPV1 and chloride channel anoctamin 1 causes enhancement of the capsaicin-evoked pain sensation in mice in collaboration with Dr. Uta (Toyama University) and Dr. Furue (NIPS). This result will be published in the Proceedings of the National Academy of Sciences of the United States of America.
It has been well known for more than 10 years that capsaicin contained in capsicums causes pungent (pain) sensation through activation of capsaicin receptor TRPV1 expressed in sensory neurons. Anoctamin 1 is also known to be involved in nociception independent of TRPV1. Drs. Takayama and Tominaga found that nociceptive responses are increased by anoctamin 1 activated by TRPV1 which binds to anoctamin 1 in the analyses using sensory neurons and spinal cord of mice. In addition, they proved that chemical blockade of anoctamin 1 is effective for relief of pain induced by TRPV1 activation.
The research group focused on the two ion channel proteins, TRPV1 and anoctamin 1 in mouse sensory neurons. And, they found that anoctamin 1 activation is accompanied by TRPV1 activity and that this sequential channel activation enhances capsaicin-evoked pain sensation.
Capsaicin-evoked burning pain sensation is induced by neural excitation through activation of TRPV1 in sensory neurons. While hot water activates TRPV1, capsaicin is stronger stimulus for TRPV1. Because TRPV1 is a non-selective cation channel, people believed that Na+ ion influx through TRPV1 pore causes depolarization, leading to the action potential generation (Figure 1, left). In this study, however, the research found a novel pain-enhancing mechanism in which anotamin 1 activated by Ca2+ ions entering cells through TRPV1 causes chloride efflux because intracellular chloride concentrations are high in the sensory neurons, which leads to further depolarization. In addition, the research group found that the functional interaction is based on their physical binding, indicating that Ca2+ ions work in the nanodomain within 20 nm distance (Figure 1, right). Furthermore, the research group observed that pain-related licking behaviors in mouse hind paws given capsaicin were inhibited by an anoctamin 1 blocker (Figure 2). Protein produced in the sensory neuron cell bodies are believed to be transferred not only to the peripheral sensory nerve endings, but also to the presynaptic terminals of the primary afferent neurons. Nociceptive signal transmission from primary afferent neurons to the second neurons in spinal cord was also reduced by anoctamin 1 blockade. Thus, anoctamin 1 blockade is useful to reduce the TRPV1-mediated pain responses.
Anoctamin1 blockade inhibits capsaicin-evoked pain-related behaviors. Credit: National Institute for Physiological Sciences
An old mechanisms (left): 1) capsaicn activates TRPV1, 2) Na+ ions enter sensory neurons through the TRPV1 pore, 3) action potentials are generated (neurons are excited). A novel mechanism (right): capsaicn activates TRPV1, 2) Ca2+ ions enter sensory neurons through the TRPV1 pore, 3) because intracellular chloride concentrations are high in the sensory neurons, chloride ion efflux is induced by anoctamin 1 activated by Ca2+ ions within 20 nm distance from TRPV1 through physical binding of the two proteins, 4) action potentials are generated. Thus, capsaicin-induced inward currents are composed of two components: TRPV1-mediated Na+ influx and anon efflux through anotamin 1 activated by Ca2+ ions entering cells through TRPV1.
Nociceptive information transmission upon capsaicin application was in inhibited by an anoctamin 1 blocker. Credit: National Institute for Physiological Sciences
Mice keep licking their hind paws upon capsaicin injection. Time spent for licking for 5 min was reduced by concomitant application of an anoctamin1 blocker.
Nociceptive signals are transmitted from the primary afferent neurons to the second neurons in spinal cord with a neurotransmitter glutamate. The electric signals can be observed (a red arrow). Capsaicin increases such electric signals. However, the increase was reduced by an anoctamin 1 blocker.
Explore further: Pepper and halt: Spicy chemical may inhibit gut tumors
More information: Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in sensory neurons, PNAS, http://ift.tt/1F7m6Ye
Journal reference: Proceedings of the National Academy of Sciences
Provided by National Institutes of Natural Sciences
Medical Xpress on facebook
Related Stories
Pepper and halt: Spicy chemical may inhibit gut tumors
Researchers at the University of California, San Diego School of Medicine report that dietary capsaicin – the active ingredient in chili peppers – produces chronic activation of a receptor on cells lining ...
Too hot to handle! Scientists identify heat sensing regulator
Neuroscientists at Johns Hopkins are a step closer to understanding pain sensitivity - specifically why it’s variable instead of constant - having identified a gene that regulates a heat-activated molecular sensor. Their ...
Putting the fire out with light
Chili peppers contain an activator of heat-sensitive pain receptors. An LMU team has now converted an antagonist to the compound into a light-sensitive regulator of such receptors that can differentially ...
Scientists discover pain receptor on T-cells
Researchers at University of California, San Diego School of Medicine have discovered that T-cells – a type of white blood cell that learns to recognize and attack microbial pathogens – are activated by a pain receptor.
Blocking pain receptors found to extend lifespan in mammals
Blocking a pain receptor in mice not only extends their lifespan, it also gives them a more youthful metabolism, including an improved insulin response that allows them to deal better with high blood sugar.
Recommended for you
Near-death brain signaling accelerates demise of the heart
What happens in the moments just before death is widely believed to be a slowdown of the body's systems as the heart stops beating and blood flow ends.
Multiple sclerosis patients could benefit from brain boost
Multiple sclerosis patients could one day benefit from treatments that boost their brain function, a study suggests.
Study provides new insight into what occurs in the brain during the learning process
Why are some people able to master a new skill quickly while others require extra time or practice? That was the question posed by UC Santa Barbara's Scott Grafton and colleagues at the University of Pennsylvania ...
Neurologic function, temperature management in patients after cardiac arrest
Quality of life was good and cognitive function was similar in patients with cardiac arrest who received targeted body-temperature management as a neuroprotective measure in intensive care units in Europe and Australia, according ...
Toward a model of synchrony in brain networks
(MedicalXpress)—Resting state networks (RSNs) in the brain are topographies of neural structures between which lag states propagate due to fluctuations of physical and other activities. Studying these networks ...
Deconstructing brain systems involved in memory and spatial skills
In work that reconciles two competing views of brain structures involved in memory and spatial perception, researchers at University of California, San Diego School of Medicine have conducted experiments ...
User comments
Please sign in to add a comment. Registration is free, and takes less than a minute. Read more
Click here
to reset your password.
Sign in to get notified via email when new comments are made.
0 comments:
Post a Comment