The mechanisms of cold encoding

Lewis, Cheyanne M; Griffith, Theanne N.

doi:10.1016/j.conb.2022.102571

Cited by 9 publications

(2 citation statements)

References 98 publications

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“…In identifying candidate thermosensors in notothenioids, I focused on TRP channels expressed in the sensory nerves. Several other channels have been proposed as possible mechanisms of temperature sensation in the cold including potassium, sodium, and P2X receptor channels (recently reviewed in [ 76 ]). Data from mammals indicates primary keratinocytes amplify thermal signals via an unknown molecular mechanism, potentially modulating the activity of sensory afferents [ 77 ].…”

Section: Resultsmentioning

confidence: 99%

Temperature activated transient receptor potential ion channels from Antarctic fishes

York

2023

Open Biol.

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Antarctic notothenioid fishes (cryonotothenioids) live in waters that range between −1.86°C and an extreme maximum +4°C. Evidence suggests these fish sense temperature peripherally, but the molecular mechanism of temperature sensation in unknown. Previous work identified transient receptor potential (TRP) channels TRPA1b, TRPM4 and TRPV1a as the top candidates for temperature sensors. Here, cryonotothenioid TRPA1b and TRPV1a are characterized using Xenopus oocyte electrophysiology. TRPA1b and TRPV1a showed heat-evoked currents with Q10s of 11.1 ± 2.2 and 20.5 ± 2.4, respectively. Unexpectedly, heat activation occurred at a threshold of 22.9 ± 1.3°C for TRPA1b and 32.1 ± 0.6°C for TRPV1a. These fish have not experienced such temperatures for at least 15 Myr. Either (1) another molecular mechanism underlies temperature sensation, (2) these fishes do not sense temperatures below these thresholds despite having lethal limits as low as 5°C, or (3) native cellular conditions modify the TRP channels to function at relevant temperatures. The effects of osmolytes, pH, oxidation, phosphorylation, lipids and accessory proteins were tested. No conditions shifted the activity range of TRPV1a. Oxidation in combination with reduced cholesterol significantly dropped activation threshold of TRPA1b to 11.3 ± 2.3°C, it is hypothesized the effect may be due to lipid raft disruption.

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Section: Resultsmentioning

confidence: 99%

Temperature activated transient receptor potential ion channels from Antarctic fishes

York

2023

Open Biol.

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“…This time, the cold zones were kept above freezing levels (i.e., >0°C) to persuade mice to explore the entire arena while reducing autonomous reflexes associated with physical pain. Yet, it has been reported that temperatures lower than 12°C are still perceived as significantly noxious ( Lewis and Griffith, 2022 ). To facilitate spatial orientation and the formation of a spatial-based memory that represented the safety zone, visual cues were added to the walls of the box to differentiate the safety zone (with plus symbols) from the other zones (vertical bars).…”

Section: Methodsmentioning

confidence: 99%

Prefrontal Regulation of Safety Learning during Ethologically Relevant Thermal Threat

Felix-Ortiz,

Terrell,

Gonzalez

et al. 2024

eNeuro

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Learning and adaptation during sources of threat and safety are critical mechanisms for survival. The prelimbic (PL) and infralimbic (IL) subregions of the medial prefrontal cortex (mPFC) have been broadly implicated in the processing of threat and safety. However, how these regions regulate threat and safety during naturalistic conditions involving thermal challenge still remains elusive. To examine this issue, we developed a novel paradigm in which adult mice learned that a particular zone that was identified with visuospatial cues was associated with either a noxious cold temperature (“threat zone”) or a pleasant warm temperature (“safety zone”). This led to the rapid development of avoidance behavior when the zone was paired with cold threat or approach behavior when the zone was paired with warm safety. During a long-term test without further thermal reinforcement, mice continued to exhibit robust avoidance or approach to the zone of interest, indicating that enduring spatial-based memories were formed to represent the thermal threat and thermal safety zones. Optogenetic experiments revealed that neural activity in PL and IL was not essential for establishing the memory for the threat zone. However, PL and IL activity bidirectionally regulated memory formation for the safety zone. While IL activity promoted safety memory during normal conditions, PL activity suppressed safety memory especially after a stress pre-treatment. Therefore, a working model is proposed in which balanced activity between PL and IL is favorable for safety memory formation, whereas unbalanced activity between these brain regions is detrimental for safety memory after stress.Significance StatementThis study provides new insights on the role of prefrontal cortical processing for threat and safety learning during thermal challenge. For this, a novel behavioral paradigm was implemented in which laboratory mice learned that a particular spatial zone was associated with either a noxious cold temperature (“thermal threat”) or a pleasant warm temperature (“thermal safety”). Manipulations of neuronal activity revealed that the prelimbic and infralimbic subregions of the medial prefrontal cortex bidirectionally regulated memory formation for the thermal safety zone, but not for the thermal threat zone. In addition, the influence of these cortical regions during safety memory formation was altered when mice underwent a stress treatment to produce a disease-like state.

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Slow depolarizing electrical stimuli reveal differential time courses of nociceptor recovery after prolonged topical capsaicin in human skin

Tumbala Gutti,

Carr,

Schmelz

et al. 2024

European Journal of Pain

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BackgroundWe examined de‐functionalization and temporal functional recovery of C‐nociceptor evoked pain after topical 8% capsaicin applied for 4 consecutive days.MethodsCapsaicin and placebo patches were applied to human forearm skin (n = 14). Cold, warmth and heat pain thresholds, pain NRS to electrical and thermal (48°C, 5 s) stimuli and axon reflex flare were recorded weekly for 49 days. Mechanical and heat sensitive (‘polymodal’) nociceptors were activated by single electrical half‐period sinusoidal pulses (0.5 s, 1 Hz). Mechanical and heat insensitive (‘silent’) nociceptors were activated by 4 Hz sinusoidal stimuli.ResultsCapsaicin abolished heat pain. Sensation to electrical sinusoidal stimulation was reduced but never abolished during the treatment. Pain to electrical 1 Hz ‘polymodal’ nociceptor stimulation took longer to recover than pain ratings to 4 Hz 2.5 s sinusoidal stimulation activating ‘polymodal’ and ‘silent’ nociceptors (35 vs. 21 days). Heat pain was indifferent to placebo from day 21–49. Axon reflex flare was abolished during capsaicin and only recovered to ~50% even after 49 days.ConclusionsCapsaicin abolishes heat transduction at terminal nociceptive endings, whereas small‐diameter axons sensitive to sinusoidal electrical stimulation can still be activated. 1 Hz depolarizing stimuli evoke burst discharges, as demonstrated before, and recover slower after capsaicin than single pulses induced by 4 Hz. The difference in recovery suggests differential time course of functional regeneration for C‐nociceptor sub‐types after capsaicin. All sensations recovered completely within 7 weeks in healthy subjects. Our findings contrast analgesia lasting for months in spontaneous neuropathic pain patients treated with 8% capsaicin.SignificanceSinusoidal electrical stimulation can still activate small diameter axons desensitized to heat after 4 consecutive days of topical 8% capsaicin application and reveals differential temporal functional regeneration of C‐nociceptor sub‐types. Electrical sinusoidal stimulation may detect such axons that no longer respond to heat stimuli in neuropathic skin.

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The mechanisms of cold encoding

Cited by 9 publications

References 98 publications

Temperature activated transient receptor potential ion channels from Antarctic fishes

Temperature activated transient receptor potential ion channels from Antarctic fishes

Prefrontal Regulation of Safety Learning during Ethologically Relevant Thermal Threat

Slow depolarizing electrical stimuli reveal differential time courses of nociceptor recovery after prolonged topical capsaicin in human skin

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