Bovine lactoferrin reduces extra-territorial facial allodynia/hyperalgesia following a trigeminal nerve injury in the rat

Horie, Kayo; Watanabe, Mineo; Chea, Chanbora; Awada, Tetsuya; Kunimatsu, Ryo; Uchida, Takashi; Takata, Takashi; Tanimoto, Kotaro

doi:10.1016/j.brainres.2017.04.015

Cited by 9 publications

(13 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is very well conceivable that drugs that primarily act on sensitization processes in the nociceptive system may work better in thoracolumbar PHN than in trigeminal PHN. 10 Facing future studies, it would therefore be interesting to include an analysis of the treatment results in regard to subgroups based on the localisation of pain in patients with PHN. 5 …”

Section: Discussionmentioning

confidence: 99%

Sensory symptom profiles differ between trigeminal and thoracolumbar postherpetic neuralgia

et al. 2018

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Sensory symptom profiles differ between trigeminal and thoracolumbar postherpetic neuralgia

et al. 2018

View full text Add to dashboard Cite

show abstract

“…<1> GDNF [38], Patched-1 (Hedgehog pathway readout) mRNA [36] <6> CGRP [30] Trigeminal ganglion Upregulation: [31], p-IκB kinase [31], p-NF-κB p65 [31], p-p38 [31] <13> EphA4 [69], IL-1β [70], JAK2 [71], p-NF-κB [72], p-p38 [72], PTEN [71], VEGF [73] <11> ATF-3 [33], BrdU (mitotic marker) [33], CD11b [33], GFAP [33], NK1 receptor [33] <12> p-ERK [34] <13> OX-42 (microglial activation) [35,74], PPARG [75] Downregulation: <1> Glutamate transporter 1 [76] <9> GRK2 [70] <10> KCC2 [77] <11> CGRP [33], GAD65 [78], SP [33] Upper central nervous system Upregulation: [95], Gabapentin/ip/mech. [95], Gabapentin/po/mech., spon.…”

Section: Trigeminal Neuron (Axon)mentioning

confidence: 99%

Potential Molecular Targets for Treating Neuropathic Orofacial Pain Based on Current Findings in Animal Models

Nagakura

Nagaoka

Kurose

2021

IJMS

View full text Add to dashboard Cite

This review highlights potential molecular targets for treating neuropathic orofacial pain based on current findings in animal models. Preclinical research is currently elucidating the pathophysiology of the disease and identifying the molecular targets for better therapies using animal models that mimic this category of orofacial pain, especially post-traumatic trigeminal neuropathic pain (PTNP) and primary trigeminal neuralgia (PTN). Animal models of PTNP and PTN simulate their etiologies, that is, trauma to the trigeminal nerve branch and compression of the trigeminal root entry zone, respectively. Investigations in these animal models have suggested that biological processes, including inflammation, enhanced neuropeptide-mediated pain signal transmission, axonal ectopic discharges, and enhancement of interactions between neurons and glial cells in the trigeminal pathway, are underlying orofacial pain phenotypes. The molecules associated with biological processes, whose expressions are substantially altered following trigeminal nerve damage or compression of the trigeminal nerve root, are potentially involved in the generation and/or exacerbation of neuropathic orofacial pain and can be potential molecular targets for the discovery of better therapies. Application of therapeutic candidates, which act on the molecular targets and modulate biological processes, attenuates pain-associated behaviors in animal models. Such therapeutic candidates including calcitonin gene-related peptide receptor antagonists that have a reasonable mechanism for ameliorating neuropathic orofacial pain and meet the requirements for safe administration to humans seem worth to be evaluated in clinical trials. Such prospective translation of the efficacy of therapeutic candidates from animal models to human patients would help develop better therapies for neuropathic orofacial pain.

show abstract

“…According to these findings, and assuming that tissue damage drives the release of DAMPs as ligands of TLR4, Figure 1 represents the presumable role of bLf on the DAMP-TLR4-TRAF6-NFκB signaling pathway that ameliorates the inflammatory response associated with nociceptive responses. ministration of bLf is subsequently endocytosed via LRP1 to bind to endogenous TRAF6 [29]. Due to binding to TRAF6, bLf decreased the expression of p-p38 in microglia; p-p65 in astrocytes; and p-38, p-p65, p-IKKβ, IL18, and TNFα in the brains of neuropathic rats [29].…”

Section: Mechanisms Of Action Underlying the Anti-nociceptive Activity Of Lactoferrin 41 Role Of The Traf6-nfκb Signaling Pathwaymentioning

confidence: 99%

“…In this regard, bLf modulates pro-inflammatory cytokine generation [ 43 ], iron absorption [ 44 ], and the production of reactive oxide species (ROS) and reactive nitrogen species (RNS) [ 45 , 46 ]. These properties seem to be intimately intermingled with the anti-nociceptive and anti-inflammatory effects of bLf [ 16 , 29 , 47 ], which will be described in more detail in the following section.…”

Section: Lactoferrin Overviewmentioning

confidence: 99%

“…Bovine lactoferrin is a multifunctional, iron-binding glycoprotein with anti-inflammatory effects produced by reducing the activation of neural inflammatory signaling pathways associated with pain [ 29 ]. Taking into account their effects against pain, potential therapeutic and prophylactic applications of bLf and bLf-peptide derivatives to several pathologic conditions—for example, osteoarthritis—have been proposed [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lactoferrin and Its Potential Impact for the Relief of Pain: A Preclinical Approach

2021

View full text Add to dashboard Cite

Pain is one of the most disabling symptoms of several clinical conditions. Neurobiologically, it is classified as nociceptive, inflammatory, neuropathic and dysfunctional. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are conventionally prescribed for the treatment of pain. Long-term administration of opioids results in the loss of analgesic efficacy, leading to increased dosage, tolerance, and addiction as the main drawbacks of their use, while the adverse effects of NSAIDs include gastric ulcer formation, intestinal bleeding, acute kidney injury, and hepatotoxicity. Lactoferrin is an iron-binding, anti-inflammatory glycoprotein that displays analgesic activities associated, in part, by interacting with the low-density lipoprotein receptor-related protein (LRP), which may result in the regulation of the DAMP–TRAF6–NFκB, NO–cGMP–ATP K+-sensitive channel and opioid receptor signaling pathways. This review summarizes and discusses for the first time the analgesic effects of lactoferrin and its presumable mechanisms based on pre-clinical trials. Given its anti-nociceptive and anti-inflammatory properties, lactoferrin may be used as an adjunct to enhance the efficacy and to decrease the tolerogenic effects of canonical therapeutic drugs prescribed for pain treatment.

show abstract

Bovine lactoferrin reduces extra-territorial facial allodynia/hyperalgesia following a trigeminal nerve injury in the rat

Cited by 9 publications

References 42 publications

Sensory symptom profiles differ between trigeminal and thoracolumbar postherpetic neuralgia

Sensory symptom profiles differ between trigeminal and thoracolumbar postherpetic neuralgia

Potential Molecular Targets for Treating Neuropathic Orofacial Pain Based on Current Findings in Animal Models

Lactoferrin and Its Potential Impact for the Relief of Pain: A Preclinical Approach

Contact Info

Product

Resources

About