IL-1 receptor antagonist improves morphine and buprenorphine efficacy in a rat neuropathic pain model

Piłat, Dominika; Rojewska, Ewelina; Jurga, Agnieszka M.; Piotrowska, Anna; Makuch, Wioletta; Przewłocka, Barbara; Mika, Joanna

doi:10.1016/j.ejphar.2015.05.058

Cited by 43 publications

(54 citation statements)

References 63 publications

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“…Our current study indicated that the CCI-induced development of tactile and thermal hypersensitivity is associated with the upregulation of IL-1beta in the spinal cord and DRG, which is in agreement with previous reports (Pilat et al 2015). Additionally, we demonstrated for the first time that RS504393 prevented the CCI-elevated upregulation of pronociceptive IL-1beta in both examined structures, suggesting that this can be one of the reasons of its strong analgesic properties.…”

Section: Discussionsupporting

confidence: 94%

“…We observed that the CCI induced no changes in IL-1R1 in the spinal cord and only slightly decreased its level in the DRG. After the nerve injury the presence of IL-1R1 on sensory neurons suggests the possibility that IL-1beta might directly influence nociceptive transmission (Oka et al 1994; Obreja et al 2002), therefore IL-1RA successfully decreases neuropathic pain (Pilat et al 2015). We assume that IL-1R1 is functionally active and that its turnover might be enhanced in pathology.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it was recently reported that intrathecal IL-10 gene therapy resulted in profound neuropathic pain relief in several animal models (Milligan et al 2006; Ledeboer et al 2007). Previous studies have also shown that intracerebroventricular injections of exogenous IL-1beta reduced the analgesic effect of morphine (Gul et al 2000; Rady and Fujimoto 2001), whereas chronic administration of IL-1RA (Pilat et al 2015), IL-18BP (Pilat et al 2016), sTNFR, and anti-IL-6 antibody (Raghavendra et al 2002) partially restored morphine efficacy in neuropathic rats. Additionally, a single intrathecal injection of IL-1RA and IL-18BP improved the analgesic efficiency of both morphine and buprenorphine in sciatic nerve-injured rats (Pilat et al 2015, 2016).…”

Section: Introductionmentioning

confidence: 93%

“…Undoubtedly, alongside neuronal pathways, activated glial cells that produce nociceptive factors, such as interleukins and chemokines, are of key importance for pain transmission under neuropathy (Gao and Ji 2010; Kiguchi et al 2012; Old et al 2015). Until now, it has been well established that the disrupted equilibrium between pro- and antinociceptive factors contributes to the development of neuropathic pain (Rojewska et al 2014b; Pilat et al 2015, 2016). …”

Section: Introductionmentioning

confidence: 99%

“…Several studies have shown that intrathecal/intracerebroventricular injections of IL-1beta (Oka et al 1994; Mika et al 2008) and IL-6 (Oka et al 1995) induced pain-related behavior, whereas intrathecal administration of IL-1alpha (Mika et al 2008), IL-1 receptor antagonist (IL-1RA) (Milligan et al 2006; Ledeboer et al 2007; Pilat et al 2015) and IL-18 binding protein (IL-18BP) (Pilat et al 2016) attenuated neuropathic pain in rats. Moreover, it was recently reported that intrathecal IL-10 gene therapy resulted in profound neuropathic pain relief in several animal models (Milligan et al 2006; Ledeboer et al 2007).…”

Section: Introductionmentioning

confidence: 99%

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The RS504393 Influences the Level of Nociceptive Factors and Enhances Opioid Analgesic Potency in Neuropathic Rats

Kwiatkowski

Piotrowska

Rojewska

et al. 2017

J Neuroimmune Pharmacol

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Increasing evidence has indicated that activated glial cells releasing nociceptive factors, such as interleukins and chemokines, are of key importance for neuropathic pain. Significant changes in the production of nociceptive factors are associated with the low effectiveness of opioids in neuropathic pain. Recently, it has been suggested that CCL2/CCR2 signaling is important for nociception. Here, we studied the time course changes in the mRNA/protein level of CD40/Iba-1, CCL2 and CCR2 in the spinal cord/dorsal root ganglia (DRG) in rats following chronic constriction injury (CCI) of the sciatic nerve. Moreover, we examined the influence of intrathecal preemptive and repeated (daily for 7 days) administration of RS504393, CCR2 antagonist, on pain-related behavior and the associated biochemical changes of some nociceptive factors as well as its influence on opioid effectiveness. We observed simultaneous upregulation of Iba-1, CCL2, CCR2 in the spinal cord on 7th day after CCI. Additionally, we demonstrated that repeated administration of RS504393 not only attenuated tactile/thermal hypersensitivity but also enhanced the analgesic properties of morphine and buprenorphine under neuropathy. Our results proof that repeated administration of RS504393 reduced the mRNA and/or protein levels of pronociceptive factors, such as IL-1beta, IL-18, IL-6 and inducible nitric oxide synthase (iNOS), and some of their receptors in the spinal cord and/or DRG. Furthermore, RS504393 elevated the spinal protein level of antinociceptive IL-1alpha and IL-18 binding protein. Our data provide new evidence that CCR2 is a promising target for diminishing neuropathic pain and enhancing the opioid analgesic effects.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The RS504393 Influences the Level of Nociceptive Factors and Enhances Opioid Analgesic Potency in Neuropathic Rats

Kwiatkowski

Piotrowska

Rojewska

et al. 2017

J Neuroimmune Pharmacol

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Ginsenoside Rf relieves mechanical hypersensitivity, depression‐like behavior, and inflammatory reactions in chronic constriction injury rats

Chen

et al. 2019

Phytotherapy Research

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The aim of this study was to investigate whether ginsenoside Rf can effectively relieve pain hypersensitivity in a neuropathic pain rat model. Neuropathic pain was induced in rats by chronic constriction injury (CCI) to the right sciatic nerve. Ginsenoside Rf was administered intraperitoneally after CCI surgery. The von Frey filament test and forced swimming test were performed to examine pain hypersensitivity and depression-like behavior in rats. Western blot was used to measure the levels of inflammatory cytokines in the dorsal root ganglion (DRG) and the spinal cord. Pretreatment of ginsenoside Rf for 7 days did not affect the onset of mechanical allodynia in CCI rats; however, a single dose of ginsenoside Rf 1 day after surgery attenuated established mechanical allodynia in CCI rats. Additionally, chronic treatment of ginsenoside Rf 1 week before and 2 weeks after CCI surgery diminished mechanical allodynia and depression-like behavior without affecting spontaneous locomotor activity in CCI rats. Furthermore, in CCI rats, chronic ginsenoside Rf treatment partially reversed the upregulation of proinflammatory cytokines in the spinal cord and/or the DRG but elevated IL-10, an anti-inflammatory factor, in the DRG. Ginsenoside Rf alleviated neuropathic pain and its associated depression and restored the balance between proinflammatory and anti-inflammatory cytokines. Our results suggest that ginsenoside Rf may be a potential therapy for nerve injury-induced neuropathic pain.

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Review of Neuraxial Agents Producing Analgesia

Dias,

Sorkin,

Yaksh

2023

Neuraxial Therapeutics

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IL-1 receptor antagonist improves morphine and buprenorphine efficacy in a rat neuropathic pain model

Cited by 43 publications

References 63 publications

The RS504393 Influences the Level of Nociceptive Factors and Enhances Opioid Analgesic Potency in Neuropathic Rats

The RS504393 Influences the Level of Nociceptive Factors and Enhances Opioid Analgesic Potency in Neuropathic Rats

Ginsenoside Rf relieves mechanical hypersensitivity, depression‐like behavior, and inflammatory reactions in chronic constriction injury rats

Review of Neuraxial Agents Producing Analgesia

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