Glial Modulation in Pain States

Horvath, Ryan J.; Romero‐Sandoval, E. Alfonso; Leo, Joyce A. De

doi:10.1201/9781439812105-c9

Cited by 3 publications

(5 citation statements)

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“…Such lack of effective analgesia with morphine over time is characteristic of many neuropathic pain patients 67– 69 . Since each of the three doses of morphine in this study is separated by weeks, the weakening response to morphine does not reflect tolerance but a resistance.…”

Section: Discussionmentioning

confidence: 99%

“…An opioid related hypersensitivity 65 , 66 or resistance is suggested by the data as seen in the GEL and 5/8 sham animals ( Figure 7 ). Such lack of effective analgesia with morphine over time is characteristic of many neuropathic pain patients 67 – 69 . Since each of the three doses of morphine in this study is separated by weeks, the weakening response to morphine does not reflect tolerance but a resistance.…”

Section: Discussionmentioning

confidence: 99%

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The refined biomimetic NeuroDigm GEL™ model of neuropathic pain in a mature rat

et al. 2017

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Background: Many humans suffering with chronic neuropathic pain have no objective evidence of an etiological lesion or disease. Frequently their persistent pain occurs after the healing of a soft tissue injury. Based on clinical observations over time, our hypothesis was that after an injury in mammals the process of tissue repair could cause chronic neural pain. Our objectives were to create the delayed onset of neuropathic pain in rats with minimal nerve trauma using a physiologic hydrogel, and characterize the rats’ responses to known analgesics and a targeted biologic. Methods: In mature male Sprague Dawley rats (age 9.5 months) a percutaneous implant of tissue-derived hydrogel was placed in the musculofascial tunnel of the distal tibial nerve. Subcutaneous morphine (3 mg/kg), celecoxib (10 mg/kg), gabapentin (25 mg/kg) and duloxetine (10 mg/kg) were each screened in the model three times each over 5 months after pain behaviors developed. Sham and control groups were used in all screenings. A pilot study followed in which recombinant human erythropoietin (200 units) was injected by the GEL™ neural procedure site. Results: The GEL group gradually developed mechanical hypersensitivity lasting months. Morphine, initially effective, had less analgesia over time. Celecoxib produced no analgesia, while gabapentin and duloxetine at low doses demonstrated profound analgesia at all times tested. The injected erythropoietin markedly decreased bilateral pain behavior that had been present for over 4 months, p ≤ 0.001. Histology of the GEL group tibial nerve revealed a site of focal neural remodeling, with neural regeneration, as found in nerve biopsies of patients with neuropathic pain. Conclusion: The refined NeuroDigm GEL™ model induces a neural response resulting in robust neuropathic pain behavior. The analgesic responses in this model reflect known responses of humans with neuropathic pain. The targeted recombinant human erythropoietin at the ectopic neural lesion appears to alleviate the persistent pain behavior in the GEL™ model rodents.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The refined biomimetic NeuroDigm GEL™ model of neuropathic pain in a mature rat

et al. 2017

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“…Specifically, they modify the balance between anti- and pro-inflammatory cytokines. Multiple glial cell modulators, such as fluorocitrate, ibudilast, minocycline, naltrexone, and propentofylline [ 14 , 15 ], have been assessed in clinical trials. However, the development of drugs targeting neuroinflammation is still in its infancy and needs to be further advanced.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic Insight into the Effects of Curcumin on Neuroinflammation-Driven Chronic Pain

et al. 2021

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Chronic pain is a persistent and unremitting condition that has immense effects on patients’ quality of life. Studies have shown that neuroinflammation is associated with the induction and progression of chronic pain. The activation of microglia and astrocytes is the major hallmark of spinal neuroinflammation leading to neuronal excitability in the projection neurons. Excessive activation of microglia and astrocytes is one of the major contributing factors to the exacerbation of pain. However, the current chronic pain treatments, mainly by targeting the neuronal cells, remain ineffective and unable to meet the patients’ needs. Curcumin, a natural plant product found in the Curcuma genus, improves chronic pain by diminishing the release of inflammatory mediators from the spinal glia. This review details the role of curcumin in microglia and astrocytes both in vitro and in vivo and how it improves pain. We also describe the mechanism of curcumin by highlighting the major glia-mediated cascades in pain. Moreover, the role of curcumin on inflammasome and epigenetic regulation is discussed. Furthermore, we discuss the strategies used to improve the efficacy of curcumin. This review illustrates that curcumin modulating microglia and astrocytes could assure the treatment of chronic pain by suppressing spinal neuroinflammation.

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“…Marijuana acts on both CB1 receptors, which modulate pain and euphoria, and CB2 receptors on glial cells. Curiously, there is preclinical evidence to support the use of CB2-specific cannabinoid agonists in pain because they lack the neurological adverse effects associated with marijuana mediated via CB1 receptors as they do not seem to be subject to the same degree of tolerance development; and they are potent glial modifiers with the potential to reduce altered central immune signaling [11]. The clinical development of CB2-specific agents may dramatically alter the way we administer chronic opioids.…”

Section: Five-year Viewmentioning

confidence: 99%

“…This ineffectiveness can contribute to an apparent undermedication, resulting in pseudoaddictive drug-seeking behavior. Moreover, as glial cells in the CNS are now understood to play a major role in the development of neuropathic pain, OIH and opioid tolerance, it has been postulated that altered glial cell behavior may contribute to opioid abuse [11]. Variation in sensitivity to drug effect, drug metabolism and adaptation to the effects of chronic exposure to a drug may also contribute to the susceptibility for opioid abuse.…”

Section: Medscape: Continuing Medical Education Onlinementioning

confidence: 99%