Morphine Efficacy, Tolerance, and Hypersensitivity Are Altered After Modulation of SUR1 Subtype KATP Channel Activity in Mice

Fisher, Cole; Johnson, Kayla; Okerman, Travis; Jurgenson, Taylor; Nickell, Austin; Salo, Erin; Moore, Mackenzie; Doucette, Alexis; Bjork, James A.; Klein, Amanda H.

doi:10.3389/fnins.2019.01122

Cited by 23 publications

(14 citation statements)

References 94 publications

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“…Injury did not affect ATP sensitivity, inward rectification, unitary conductance or the pharmacological properties of K ATP channels. Although the anti-nociceptive actions of K ATP channel openers has been recognized for many years (Vergoni et al, 1992;Welch and Dunlow, 1993), much of the preclinical work has dealt with the ability of drugs such as pinacidil to potentiate opioid action (Vergoni et al, 1992;Fisher et al, 2019). The relevance of this to therapeutic management of neuropathic pain is yet to be explored.…”

Section: ) Channels In Primary Afferent Neurons and Effect Of Nerve mentioning

confidence: 99%

K+ Channels in Primary Afferents and Their Role in Nerve Injury-Induced Pain

Smith

2020

Front. Cell. Neurosci.

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Sensory abnormalities generated by nerve injury, peripheral neuropathy or disease are often expressed as neuropathic pain. This type of pain is frequently resistant to therapeutic intervention and may be intractable. Numerous studies have revealed the importance of enduring increases in primary afferent excitability and persistent spontaneous activity in the onset and maintenance of peripherally induced neuropathic pain. Some of this activity results from modulation, increased activity and /or expression of voltage-gated Na + channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. K + channels expressed in dorsal root ganglia (DRG) include delayed rectifiers (K v 1.1, 1.2), A-channels (K v 1.4, 3.3, 3.4, 4.1, 4.2, and 4.3), KCNQ or M-channels (K v 7.2, 7.3, 7.4, and 7.5), ATP-sensitive channels (K IR 6.2), Ca 2+-activated K + channels (K Ca 1.1, 2.1, 2.2, 2.3, and 3.1), Na +-activated K + channels (K Ca 4.1 and 4.2) and two pore domain leak channels (K 2p ; TWIK related channels). Function of all K + channel types is reduced via a multiplicity of processes leading to altered expression and/or post-translational modification. This also increases excitability of DRG cell bodies and nociceptive free nerve endings, alters axonal conduction and increases neurotransmitter release from primary afferent terminals in the spinal dorsal horn. Correlation of these cellular changes with behavioral studies provides almost indisputable evidence for K + channel dysfunction in the onset and maintenance of neuropathic pain. This idea is underlined by the observation that selective impairment of just one subtype of DRG K + channel can produce signs of pain in vivo. Whilst it is established that various mediators, including cytokines and growth factors bring about injury-induced changes in DRG function and excitability, evidence presently available points to a seminal role for interleukin 1β (IL-1β) in control of K + channel function. Despite the current state of knowledge, attempts to target K + channels for therapeutic pain management have met with limited success. This situation may change with the advent of personalized medicine. Identification of specific sensory abnormalities and genetic profiling of individual patients may predict therapeutic benefit of K + channel activators.

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Section: ) Channels In Primary Afferent Neurons and Effect Of Nerve mentioning

confidence: 99%

K+ Channels in Primary Afferents and Their Role in Nerve Injury-Induced Pain

Smith

2020

Front. Cell. Neurosci.

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“…The activity of these channels can influence the efficacy of opioids and represent an important factor in tolerance development. Cole Fisher and co-workers demonstrated that the downregulation of SUR1 subtype K ATP channels in the spinal cord and DRG potentiated the development of morphine tolerance and withdrawal syndrome in mice [124]. SUR1 agonists (diazoxide and NN-414) attenuated tolerance development.…”

Section: The Consequence Of Mors Activation On Primary Sensory Neuronsmentioning

confidence: 99%

On the Role of Peripheral Sensory and Gut Mu Opioid Receptors: Peripheral Analgesia and Tolerance

et al. 2020

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There is growing evidence on the role of peripheral µ-opioid receptors (MORs) in analgesia and analgesic tolerance. Opioid analgesics are the mainstay in the management of moderate to severe pain, and their efficacy in the alleviation of pain is well recognized. Unfortunately, chronic treatment with opioid analgesics induces central analgesic tolerance, thus limiting their clinical usefulness. Numerous molecular mechanisms, including receptor desensitization, G-protein decoupling, β-arrestin recruitment, and alterations in the expression of peripheral MORs and microbiota have been postulated to contribute to the development of opioid analgesic tolerance. However, these studies are largely focused on central opioid analgesia and tolerance. Accumulated literature supports that peripheral MORs mediate analgesia, but controversial results on the development of peripheral opioid receptors-mediated analgesic tolerance are reported. In this review, we offer evidence on the consequence of the activation of peripheral MORs in analgesia and analgesic tolerance, as well as approaches that enhance analgesic efficacy and decrease the development of tolerance to opioids at the peripheral sites. We have also addressed the advantages and drawbacks of the activation of peripheral MORs on the sensory neurons and gut (leading to dysbiosis) on the development of central and peripheral analgesic tolerance.

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“…Through influencing the central nervous system, morphine alleviates pain. However, despite the high analgesic potential, it has the potential to be highly addictive if used regularly, in which drug tolerance, physical and psychological dependence are rapidly evolved (4). Long-term use of morphine can change hypothalamus-pituitary-gonads (HPG) axis, which affects the hormones secreted by the anterior pituitary gland, including luteinizing hormone (LH) (5).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Morphine Dependence and Detoxification with Methadone and Buprenorphine on Sexual Behavior and Sex Hormones

Moinaddini

Haghpanah

Esfahlani

et al. 2021

Int J High Risk Behav Addict

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Background: Opiate dependence, a great worldwide obstacle, is regularly treated by detoxification via opioid agonists and antagonist administration. However, different effects and severity of detoxification on the male reproductive system have not been evaluated so far. Objectives: Thus, the present study intended to investigate the impact of morphine dependence and detoxification with methadone and/or buprenorphine on sexual behavior and sex hormones in an animal model of opiate dependence. Materials and Methods: sixty-six adult male mice were randomly allocated into six groups of control (ctl40), morphine-dependent (Mrph40) (which received morphine for 40 days), another control (Ctrl80), morphine-dependent (Mrph80) (which received morphine for 80 days), methadone (Mtdn) detoxified, and buprenorphine (Bprn) detoxified groups (n = 11). Different aspects of sexual activities and Sex hormones were assessed at the end of the treatment period. Data were analyzed by ANOVA test and chi-squared test using SPSS version 16 software for Windows. Results: Testosterone level significantly decreased in all treated groups compared with its level in the Ctl40 group. Detoxification with buprenorphine was reduced following 80 days of treatment, the level of testosterone significantly reduced in all treated groups compared to its level in the Ctrl80 group. The highest and lowest levels of FSH were observed in the Bprn group and in the Mrph40 group, respectively, even lower than that of the Mrph80 and Mtdn groups. Either of the treatments has decreased the level of LH when compared with its level in the controls. Various sexual behaviors were differently disturbed in the treated groups. Duration of sexual activity, Mount frequency, ejaculation latency, and sexual activity duration was higher in the Bprn group than the Mtdn group, but the rate of pregnancy was much higher in the Mtdn group. Conclusions: Either Short or long-term dependence on morphine affects the sex hormones and activities. Following detoxification with methadone and/or buprenorphine, various aspects of sexual behaviors were differently altered, which could alert clinicians in detoxification programs.

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Morphine Efficacy, Tolerance, and Hypersensitivity Are Altered After Modulation of SUR1 Subtype KATP Channel Activity in Mice

Cited by 23 publications

References 94 publications

K+ Channels in Primary Afferents and Their Role in Nerve Injury-Induced Pain

K+ Channels in Primary Afferents and Their Role in Nerve Injury-Induced Pain

On the Role of Peripheral Sensory and Gut Mu Opioid Receptors: Peripheral Analgesia and Tolerance

The Effects of Morphine Dependence and Detoxification with Methadone and Buprenorphine on Sexual Behavior and Sex Hormones

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