p38 siRNA-encapsulated PLGA nanoparticles alleviate neuropathic pain behavior in rats by inhibiting microglia activation

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.

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d-Cycloserine reduces neuropathic pain behavior through limbic NMDA-mediated circuitry☆

Pain ◽

10.1016/j.pain.2007.03.003 ◽

2007 ◽

Vol 132 (1) ◽

pp. 108-123 ◽

Cited By ~ 72

Author(s):

Magali Millecamps ◽

Maria V. Centeno ◽

Hector H. Berra ◽

Charles N. Rudick ◽

Simona Lavarello ◽

...

Keyword(s):

Neuropathic Pain ◽

Pain Behavior

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Biomarkers for microglia activation in neuropathic pain

Anaesthesia, Pain & Intensive Care ◽

10.35975/apic.v24i1.1229 ◽

2020 ◽

Vol 24 (1) ◽

pp. 87-93

Author(s):

Putu Eka Widyadharma ◽

Aurelia Vania ◽

Jimmy FA Barus ◽

Yudiyanta . ◽

Thomas Eko Purwata

Keyword(s):

Neuropathic Pain ◽

Intensive Care ◽

Microglia Activation ◽

Future Research ◽

Future Studies ◽

Activated Microglia ◽

New Therapy ◽

Promising Target ◽

Chemical Mediators

Neuropathic pain (NP) is a result of direct disturbances of somatosensory pathways. Its pathophysiology includes various mechanisms. Recent studies have reported an important role of microglia in the NP mechanism. There are several chemical molecules which are involved in microglia activation. The activated microglia will, in turn, enhance some receptors expression that can be used as markers of its activation. Though we still need future studies about precise microglia role in NP mechanism, the chemical mediators that initiate microglia activation and the alteration of some receptors in the activated microglia which have been found from previous studies can be the interesting future research materials and the promising target for a new therapy for NP. Citation: Widyadharma PE, Vania A, Barus JFA, Yudiyanta, Purwata TE. Biomarkers for microglia activation in neuropathic pain. Anaesth pain intensive care 2020;24(1):___ DOI: https://doi.org/10.35975/apic.v24i1. Received – 12 June 2019, Reviewed – 15 September 2019, 29 February 2020, Accepted – 2 March 2020;

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The refined biomimetic NeuroDigm GEL™ Model of neuropathic pain in the mature rat

F1000Research ◽

10.12688/f1000research.9544.1 ◽

2016 ◽

Vol 5 ◽

pp. 2516 ◽

Cited By ~ 1

Author(s):

Mary R. Hannaman ◽

Douglas A. Fitts ◽

Rose M. Doss ◽

David E. Weinstein ◽

Joseph L. Bryant

Keyword(s):

Neuropathic Pain ◽

Recombinant Human Erythropoietin ◽

Tissue Injury ◽

Soft Tissue Injury ◽

Pain Behavior ◽

Neural Regeneration ◽

Male Rat ◽

Human Erythropoietin ◽

Neural Remodeling ◽

Over Time

Background:Many humans suffering with chronic pain have no clinical evidence of a lesion or disease. They are managed with a morass of drugs and invasive procedures. Opiates usually become less effective over time. In many, their persistent pain occurs after the healing of a soft tissue injury. Current animal models of neuropathic pain typically create direct neural damage with open surgeries using ligatures, neurectomies, chemicals or other forms of deliberate trauma. However, we have observed clinically that after an injury in humans, the naturally occurring process of tissue repair can cause chronic neural pain.Methods:We demonstrate how the refined biomimetic NeuroDigm GEL™ Model, in the mature male rat, gradually induces neuropathic pain behavior with a nonsurgical percutaneous implant of tissue-derived hydrogel in the musculo-fascial tunnel of the distal tibial nerve. Morphine, Celecoxib, Gabapentin and Duloxetine were each screened in the model three times each over 5 months after pain behaviors developed. A pilot study followed in which recombinant human erythropoietin was applied to the GEL neural procedure site.Results:The GEL Model gradually developed neuropathic pain behavior lasting months. Morphine, initially effective, had less analgesia over time. Celecoxib produced no analgesia, while gabapentin and duloxetine at low doses had profound analgesia at all times tested. The injected erythropoietin markedly decreased bilateral pain behavior that had been present for over 4 months. Histology revealed a site of focal neural remodeling, with neural regeneration, as in human biopsies.Conclusion:The refined NeuroDigm GEL™ Model induces localized neural remodeling resulting in robust neuropathic pain behavior. The analgesics responses in this model reflect known responses of humans with neuropathic pain. The targeted recombinant human erythropoietin appears to heal the ectopic focal neural site, as demonstrated by the extinguishing of neuropathic pain behavior present for over 4 months.

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