2021
DOI: 10.1126/scitranslmed.abd7702
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Transient receptor potential canonical 5 mediates inflammatory mechanical and spontaneous pain in mice

Abstract: Tactile and spontaneous pains are poorly managed symptoms of inflammatory and neuropathic injury. Here, we found that transient receptor potential canonical 5 (TRPC5) is a chief contributor to both of these sensations in multiple rodent pain models. Use of TRPC5 knockout mice and inhibitors revealed that TRPC5 selectively contributes to the mechanical hypersensitivity associated with CFA injection, skin incision, chemotherapy induced peripheral neuropathy, sickle cell disease, and migraine, all of which were c… Show more

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Cited by 47 publications
(46 citation statements)
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“…The activation and role of amygdaloid TRPC4/TRPC5 in migraine should be further explored in future studies. Activation of TRPC5 by endogenous lysophosphatidylcholine in peripheral sensory neurons has recently emerged as a mediator of inflammatory and neuropathic pain ( Sadler et al, 2021 ). Interestingly, lysophosphatidylcholine is increased in various animal pain models and its application to meningeal tissue elicited migraine-like behavior.…”
Section: Discussionmentioning
confidence: 99%
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“…The activation and role of amygdaloid TRPC4/TRPC5 in migraine should be further explored in future studies. Activation of TRPC5 by endogenous lysophosphatidylcholine in peripheral sensory neurons has recently emerged as a mediator of inflammatory and neuropathic pain ( Sadler et al, 2021 ). Interestingly, lysophosphatidylcholine is increased in various animal pain models and its application to meningeal tissue elicited migraine-like behavior.…”
Section: Discussionmentioning
confidence: 99%
“…Further investigations should be carried out to define the endogenous agonists of TRPC4, as well as its expression with serotonergic receptors in rodent and human tissues. Of note, a discrepancy between mouse and human TRPC5 expression in peripheral sensory neurons has been reported ( Sadler et al, 2021 ), and thus a precise characterization of TRPC4 expression in human tissues will be crucial for the evaluation of the translational potential of TRPC4 as a therapeutic target.…”
Section: Discussionmentioning
confidence: 99%
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“…Although TRPC4/C5 has had pronociceptive actions in previous studies (see for review [ 19 ]), TRPC4/C5 receptor antagonists failed to attenuate mechanical hypersensitivity induced by netrin-1, except for the weak antihypersensitivity effect during the early phase by the less selective of the currently used antagonists. However, the most prominent TRPC5-induced pronociceptive effects have been demonstrated in primary afferent nerve fibers [ 28 ] rather than the spinal cord. In addition to the peripheral neurons, there is earlier evidence that TRPC4/C5 channels are involved in the control of the primary emotion center amygdala [ 29 , 30 ] which is also a key player in the processing and control of affective aspects of pain [ 31 ], and which we did not study in the present experiments.…”
Section: Discussionmentioning
confidence: 99%
“…TRPC4 and TRPC5 are non-selective cation channels that can form homomers and heteromers, and are expressed mainly in the amygdala and hippocampus. Also, these channels are expressed in the peripheral sensory neurons of rodents [ 59 ] and humans [ 60 ]. TRPC5 is considered a cold-sensitive receptor [ 17 ], but, because TRPC5 also regulates prolactin release, TRPC5 antagonists may have greater analgesic efficacy in women since prolactin promotes pain only in them.…”
Section: Classification Of the Ionic Trp Channelsmentioning
confidence: 99%