Up-regulation of spinal microglial Iba-1 expression persists after resolution of neuropathic pain hypersensitivity

Leinders, Mathias; Knaepen, Liesbeth; Kock, Marc De; Sommer, Claudia; Hermans, Emmanuel; Deumens, Ronald

doi:10.1016/j.neulet.2013.08.062

Cited by 27 publications

(28 citation statements)

References 29 publications

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“…There are many reports showing the morphological changes of activated microglia/macrophages after nerve injury in immunofluorescence studies . We observed, using Western blot analysis, a strong increase in the number of IBA‐1‐positive cells on the 7th day post‐CCI in the spinal cord and the DRG, which is in agreement with other data . Many of these works emphasize that the strong uncontrolled activation of microglia/macrophages is the cause of the development of neuropathic pain.…”

Section: Discussionsupporting

confidence: 91%

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

et al. 2020

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Summary A growing body of evidence has indicated that the release of nociceptive factors, such as interleukins and chemokines, by activated immune and glial cells has crucial significance for neuropathic pain generation and maintenance. Moreover, changes in the production of nociceptive immune factors are associated with low opioid efficacy in the treatment of neuropathy. Recently, it has been suggested that CC chemokine receptor type 1 (CCR1) signaling is important for nociception. Our study provides evidence that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with significant up‐regulation of endogenous CCR1 ligands, namely, CCL2, CCL3, CCL4, CCL6, CCL7 and CCL9 in the spinal cord and CCL2, CCL6, CCL7 and CCL9 in dorsal root ganglia (DRG). We showed that single and repeated intrathecal administration of J113863 (an antagonist of CCR1) attenuated mechanical and thermal hypersensitivity. Moreover, repeated administration of a CCR1 antagonist enhanced the analgesic properties of morphine and buprenorphine after CCI. Simultaneously, repeated administration of J113863 reduced the protein levels of IBA‐1 in the spinal cord and MPO and CD4 in the DRG and, as a consequence, the level of pronociceptive factors, such as interleukin‐1β (IL‐1β), IL‐6 and IL‐18. The data obtained provide evidence that CCR1 blockade reduces hypersensitivity and increases opioid‐induced analgesia through the modulation of neuroimmune interactions.

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Section: Discussionsupporting

confidence: 91%

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

et al. 2020

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“…It seems that interruption of interaction between oligodendrocytes and axons is sufficient to induce hyperalgesia and microglia/astrocytes do not contribute to the initiation of pain hypersensitivity in these mice. The dissociation of persistent pain hypersensitivity and glial responses has also been noticed in other models [85,86]. Further studies are expected to delineate a distinct role of neuron-glial interactions under specific pain conditions.…”

Section: Concluding Remarks and Additional Commentssupporting

confidence: 55%

Activity-triggered tetrapartite neuron–glial interactions following peripheral injury

Ren

Dubner

2016

Current Opinion in Pharmacology

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Recent studies continue to support the proposition that non-neuronal components of the nervous system, mainly glial cells and associated chemical mediators, contribute to the development of neuronal hyperexcitability that underlies persistent pain conditions. In the event of peripheral injury, enhanced or abnormal nerve input is likely the most efficient way to activate simultaneously central neurons and glia. Injury induces phenotypic changes in glia and triggers signaling cascades that engage reciprocal interactions between presynaptic terminals, postsynaptic neurons, microglia and astrocytes. While some responses to peripheral injury may help the nervous system to adapt positively to counter the disastrous effect of injury, the net effect often leads to long-lasting sensitization of pain transmission pathways and chronic pain.

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“…31,32 There can be a dissociation between pain and microglial activation also. 33,34 Once increased glial activity occurs, the altered activity can persist even after recovery from nociceptive pain behaviors, as observed for microglia and hyperalgesia at day 14. 31–34 Thus, altered glial activities may reflect the presence or persistence of a pathologic state rather than reflection of a type of nociceptive behavior.…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid Receptor Type 1 Antagonist, AM251, Attenuates Mechanical Allodynia and Thermal Hyperalgesia after Burn Injury

et al. 2014

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Background Burn injury causes nociceptive behaviors, and inflammation-related pathologic pain can lead to glial cell activation. Hypothesis tested was that burn injury activates glial cells, and cannabinoid receptor 1 (CB1R) antagonist, AM251, will decrease burn pain. Methods Anesthetized rats received 0.75cm2 third degree burn on dorsal hind paw. Vehicle or AM251 30 μg intrathecally (older rats, n = 6/group) or, either vehicle, 0.1 or 1.0 mg/kg intraperitoneally (younger rats, n = 6/group), started immediate postburn, was administered for 7 days. Mechanical allodynia and thermal hyperalgesia were tested on ventral paw for 14 days. Microglial and astroglial activity were assessed by immunocytochemistry. Results Allodynia, observed on burn side from day 1–14, was significantly (p < 0.05) attenuated by intrathecal and intraperitoneal AM251 (1 mg/kg) starting from 3 to 14 days. Hyperalgesia, observed from day 3–12, was completely (p < 0.05) reversed by intrathecal and intraperitoneal AM251 (1 mg/kg). AM251 0.1 mg/kg had no effect. Microglial activity (n = 3/time point) increased (p < 0.05) 18.5 ± 7.5 and 12.3 ± 1.6 (mean +/− SD) fold at 7 and 14 days, respectively. Astroglial activity (n = 4/time point) increased 2.9 ± 0.3 fold at day 7 only. Glial activities were unaltered by AM251. Conclusion AM251 inhibited nociceptive behaviors after burn even beyond 7-day period of administration. Although many studies have documented the utility of CB1R agonists, this study indicates that endogenous cannabinoids may have an unexpected pronociceptive effect during development of burn pain, explaining why CB1R antagonist, AM251 improves nociceptive behaviors. The decreased nociception with AM251 without altering glial activity indicates that AM251 acts further downstream of activated glial cells.

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Up-regulation of spinal microglial Iba-1 expression persists after resolution of neuropathic pain hypersensitivity

Cited by 27 publications

References 29 publications

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

Activity-triggered tetrapartite neuron–glial interactions following peripheral injury

Cannabinoid Receptor Type 1 Antagonist, AM251, Attenuates Mechanical Allodynia and Thermal Hyperalgesia after Burn Injury

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