Loss of SUR1 subtype KATP channels alters antinociception and locomotor activity after opioid administration

Sakamaki, Gerald; Johnson, Kayla; Mensinger, Megan; Hmu, Eindray; Klein, Amanda H.

doi:10.1016/j.bbr.2021.113467

Cited by 3 publications

(2 citation statements)

References 64 publications

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“…Additional supportive evidence comes from studies revealing interactions with K ATP channel activity and opioid signaling ( Lohmann and Welch, 1999a , Lohmann and Welch, 1999b , Rodrigues and Duarte, 2000 , Fisher et al, 2019 , Sakamaki et al, 2021 ). SUR1 knockout or SUR1 inhibition reduces opioid-mediated analgesia ( Rodrigues and Duarte, 2000 , Fisher et al, 2019 , Sakamaki et al, 2021 ), and diazoxide-mediated analgesia is partially reduced by knockdown or pharmacological inhibition of μ-, κ-, and δ-opioid receptors ( Lohmann and Welch, 1999a , Lohmann and Welch, 1999b ). Together with the data presented here, these findings suggest that a ketogenic diet may enhance opioid-mediated analgesia downstream of K ATP channels.…”

Section: Discussionmentioning

confidence: 94%

ATP-gated potassium channels contribute to ketogenic diet-mediated analgesia in mice

Enders¹,

Thomas²,

Lynch³

et al. 2023

Neurobiology of Pain

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Section: Discussionmentioning

confidence: 94%

ATP-gated potassium channels contribute to ketogenic diet-mediated analgesia in mice

Enders¹,

Thomas²,

Lynch³

et al. 2023

Neurobiology of Pain

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“…Additionally, loss of K ATP channels or their function in peripheral neurons has been implicated in pain perception in multiple studies [ 57 , 58 , 92 , 93 ]. For instance, expression of Kir6.1, SUR1, and SUR2 in rat spinal cord were downregulated after nerve injury [ 94 ] and knockout of SUR1 subtype resulted in the loss of the antinociceptive effect of morphine in mice [ 95 , 96 ]. Furthermore, the expression of Kir6.1/SUR2B were shown to be regulated by the inflammatory toll-like receptor 4 and NF-κB-dependent signaling, which was suggested to be a factor in the poor vasoconstriction during sepsis [ 97 ].…”

Section: Molecular Basis and Physiological Function Of K At...mentioning

confidence: 99%

ATP-Sensitive Potassium Channels in Migraine: Translational Findings and Therapeutic Potential

Clement

Guo

Jansen‐Olesen

et al. 2022

Cells

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Globally, migraine is a leading cause of disability with a huge impact on both the work and private life of affected persons. To overcome the societal migraine burden, better treatment options are needed. Increasing evidence suggests that ATP-sensitive potassium (KATP) channels are involved in migraine pathophysiology. These channels are essential both in blood glucose regulation and cardiovascular homeostasis. Experimental infusion of the KATP channel opener levcromakalim to healthy volunteers and migraine patients induced headache and migraine attacks in 82-100% of participants. Thus, this is the most potent trigger of headache and migraine identified to date. Levcromakalim likely induces migraine via dilation of cranial arteries. However, other neuronal mechanisms are also proposed. Here, basic KATP channel distribution, physiology, and pharmacology are reviewed followed by thorough review of clinical and preclinical research on KATP channel involvement in migraine. KATP channel opening and blocking have been studied in a range of preclinical migraine models and, within recent years, strong evidence on the importance of their opening in migraine has been provided from human studies. Despite major advances, translational difficulties exist regarding the possible anti-migraine efficacy of KATP channel blockage. These are due to significant species differences in the potency and specificity of pharmacological tools targeting the various KATP channel subtypes.

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ATP-Gated Potassium Channels Contribute to Ketogenic Diet-Mediated Analgesia in Mice

Enders

Thomas

Lynch

et al. 2023

Preprint

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Chronic pain is a substantial health burden and options for treating chronic pain remain minimally effective. Ketogenic diets are emerging as well-tolerated, effective therapeutic strategies in preclinical models of chronic pain, especially diabetic neuropathy. We tested whether a ketogenic diet is antinociceptive through ketone oxidation and related activation of ATP-gated potassium (KATP) channels in mice. We demonstrate that consumption of a ketogenic diet for one week reduced evoked nocifensive behaviors (licking, biting, lifting) following intraplantar injection of different noxious stimuli (methylglyoxal, cinnamaldehyde, capsaicin, or Yoda1) in mice. A ketogenic diet also decreased the expression of p-ERK, an indicator of neuronal activation in the spinal cord, following peripheral administration of these stimuli. Using a genetic mouse model with deficient ketone oxidation in peripheral sensory neurons, we demonstrate that protection against methylglyoxal-induced nociception by a ketogenic diet partially depends on ketone oxidation by peripheral neurons. Injection of tolbutamide, a KATP channel antagonist, prevented ketogenic diet-mediated antinociception following intraplantar capsaicin injection. Tolbutamide also restored the expression of spinal activation markers in ketogenic diet-fed, capsaicin-injected mice. Moreover, activation of KATP channels with the KATP channel agonist diazoxide reduced pain-like behaviors in capsaicin-injected, chow-fed mice, similar to the effects observed with a ketogenic diet. Diazoxide also reduced the number of p-ERK+ cells in capsaicin-injected mice. These data support a mechanism that includes neuronal ketone oxidation and activation of KATP channels to provide ketogenic diet-related analgesia. This study also identifies KATP channels as a new target to mimic the antinociceptive effects of a ketogenic diet.

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Loss of SUR1 subtype KATP channels alters antinociception and locomotor activity after opioid administration

Cited by 3 publications

References 64 publications

ATP-gated potassium channels contribute to ketogenic diet-mediated analgesia in mice

ATP-gated potassium channels contribute to ketogenic diet-mediated analgesia in mice

ATP-Sensitive Potassium Channels in Migraine: Translational Findings and Therapeutic Potential

ATP-Gated Potassium Channels Contribute to Ketogenic Diet-Mediated Analgesia in Mice

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