TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine

Alarcón-Alarcón, David; Cabañero, David; Andrés-López, Jorge de; Nikolaeva-Koleva, Magdalena; Giorgi, Simona; Fernández‐Ballester, Gregorio; Fernández-Carvajal, Asia; Ferrer-Montiel, Antonio

doi:10.1038/s41467-022-33835-3

Cited by 27 publications

(14 citation statements)

References 90 publications

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“…Furthermore, transient receptor potential cation channel subfamily M member 8 (TRPM8) is widely recognized as having a central role in cold sensation (Bautista et al., 2007 ) and TRPM8 is expressed in cold pain and temperature‐sensitive neurons of the dorsal root ganglia (Peier et al., 2002 ). A recent study discovered divergent roles of TRPM8 in pain modulation between male and female mice (Alarcón‐Alarcón et al., 2022 ). In addition, a study has also found one of the TRPM8 variants, rs10166942, demonstrated a gradient relationship with latitude (Key et al., 2018 ), with frequencies ranging from 5% in Nigeria (average annual temperature: 28°C) to 88% in Finland (average annual temperature: 6°C).…”

Section: Discussionmentioning

confidence: 99%

The normative values of pain thresholds in healthy Taiwanese

Pan,

Ling,

Lai

et al. 2024

Brain and Behavior

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ObjectiveQuantitative sensory testing is widely used in clinical and research settings to assess the sensory functions of healthy subjects and patients. It is of importance to establish normative values in a healthy population to provide reference for studies involving patients. Given the absence of normative values for pain thresholds in Taiwan, the aim of this study was to report the normative values for future reference in the Taiwanese population and compare the differences between male and female participants.MethodsHealthy adults without any chronic or acute pain condition were recruited. The pain thresholds were assessed over the cephalic (supraorbital area and masseter muscle) and extracephalic (medio‐volar forearm and thenar eminence) areas. The heat, cold, mechanical punctate, and pressure pain thresholds were measured with a standardized protocol. Comparisons between male and female participants were performed.ResultsOne hundred and thirty healthy participants (55 males: 30.4 ± 7.4 years; 75 females: 30.5 ± 8.1 years) finished the assessments. Male participants were less sensitive to mechanical stimuli, including pressure over masseter muscle (male vs. female: 178.5 ± 56.7 vs. 156.6 ± 58.4 kPa, p = .034) and punctate over medio‐volar forearm (male vs. female: 116.4 ± 45.2 vs. 98.7 ± 65.4 g, p = .011), compared to female participants. However, female participants were less sensitive to cold stimuli, indicated by lower cold pain thresholds over the supraorbital area (male vs. female: 18.6 ± 8.4 vs. 13.6 ± 9.3°C, p = .004), compared to male participants. No significant differences were found between sexes in other pain threshold parameters.ConclusionsWe provided the normative values of healthy male and female adults in Taiwan. This information is crucial for comparison in future pain‐related studies to identify potential hypoalgesia or hyperalgesia of tested subjects.

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Section: Discussionmentioning

confidence: 99%

The normative values of pain thresholds in healthy Taiwanese

Pan,

Ling,

Lai

et al. 2024

Brain and Behavior

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“…Primary cultures of DRG and TG sensory neurons were carried out as previously described. 20 , 29 , 30 Neurons were seeded in the soma compartment of microfluidic chambers (Millipore devices “AXIS™: Axon Investigation System”). The procedure is detailed in supplementary methods .…”

Section: Methodsmentioning

confidence: 99%

Compartmentalized primary cultures of dorsal root ganglion neurons to model peripheral pathophysiological conditions

et al. 2023

Self Cite

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Neurosensory disorders such as pain and pruritus remain a major health problem greatly impacting the quality of life, and often increasing the risk of mortality. Current pre-clinical models to investigate dysfunction of sensory neurons have shown a limited clinical translation, in part, by failing to mimic the compartmentalized nociceptor anatomy that exhibit a central compartment containing the soma and a peripheral one harboring the axon endings with distinct molecular and cellular environmental composition. Thus, there is a need to validate compartmentalized preclinical neurosensory models for investigating the pathophysiology of peripheral sensory disorders and to test drug candidates. Here, we have addressed this issue and developed a microfluidic-based preclinical nociceptor model and validated it for investigating inflammatory and neuropathic peripheral disorders. We show that this model reproduces the peripheral sensitization and resolution produced by an inflammatory soup and by the chemotherapeutic drug paclitaxel. Furthermore, compartmentalized nociceptor primary cultures were amenable to co-culture with keratinocytes in the axonal compartment. Interaction of axonal endings with keratinocytes modulated neuronal responses, consistent with a crosstalk between both cell types. These findings pave the way towards translational pre-clinical sensory models for skin pathophysiological research and drug development.

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“…For instance, it has been shown that the activation of meningeal TRPM8 by exogenous agonists can both cause and alleviate headache behaviors, depending on whether other meningeal afferents concurrently receive noxious stimuli [113,114]. A recent study using transgenic knockout TRPM8 mice suggests a protective role in promoting a faster recovery from chronic migraine-like symptoms in male mice compared to that in female mice [115]. However, another study with transgenic mice showed that TRPM8 channels or afferents are both required for the development of acute and chronic migraine-like symptoms [116].…”

Section: Trpm8mentioning

confidence: 99%

Targeting Nociceptors and Transient Receptor Potential Channels for the Treatment of Migraine

Cohen¹,

Roh²,

Lee³

2023

Preprint

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Migraine is a neurovascular disorder that affects approximately 12% of the global population. While its exact causes are still being studied, researchers believe that nociceptors in the trigeminal ganglia play a key role in the pain signals of migraine. These nociceptors innervate the intracranial meninges and convey pain signals from the meninges to the thalamus. Targeting these nociceptors is considered promising due to their accessibility and distinct molecular profile, which includes the expression of several transient receptor potential (TRP) channels. These channels have been linked to various pain conditions, including migraine. This review discusses the role and mechanisms of nociceptors in migraine, the challenges of current antimigraine drugs, and the evidence for well-studied and emerging TRP channels, particularly TRPC4, as novel targets for migraine prevention and treatment.

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TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine

Cited by 27 publications

References 90 publications

The normative values of pain thresholds in healthy Taiwanese

The normative values of pain thresholds in healthy Taiwanese

Compartmentalized primary cultures of dorsal root ganglion neurons to model peripheral pathophysiological conditions

Targeting Nociceptors and Transient Receptor Potential Channels for the Treatment of Migraine

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