Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain
Abstract
:1. Introduction
2. Calcitonin Gene-Related Peptide Function in Migraine and Neuropathic Pain
2.1. Migraine
2.2. Neuropathic Pain
3. Transient Receptor Potential Ion Channel Function in Migraine and Neuropathic Pain
3.1. Migraine
3.2. Neuropathic Pain
4. Endocannabinoid Function in Migraine and Neuropathic Pain
4.1. Migraine
4.2. Neuropathic Pain
5. Kynurenine Function in Migraine and Neuropathic Pain
5.1. Migraine
5.2. Neuropathic Pain
6. Cytokine Function in Migraine and Neuropathic Pain
6.1. Migraine
6.2. Neuropathic Pain
7. Glial Function in Migraine and Neuropathic Pain
7.1. Migraine
7.2. Neuropathic Pain
8. Discussion
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
2-AG | 2-arachidonoylglycerol |
AMPA | α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid |
AMT | anandamide membrane transporter |
ATP | adenosine triphosphate |
CBR | cannabinoid receptor |
CGRP | calcitonin gene-related peptide |
CM | chronic migraine |
CNS | central nervous system |
CRPS | complex regional pain syndrome |
CSF | cerebrospinal fluid |
DSPN | distal sensorimotor polyneuropathy |
EM | episodic migraine |
FAAH | fatty acid amide hydrolase |
FHM | familial hemiplegic migraine |
HIV | human immunodeficiency virus |
IASP | International Association for the Study of Pain |
IL | interleukin |
KYN | kynurenine |
KYNA | kynurenic acid |
L-KYN | L-kynurenine |
M0 | migraine without aura |
MA | migraine with aura |
mAbs | monoclonal antibodies |
MAGL | monoacylglycerol lipase |
MAPK | mitogen-activated protein kinase |
MRI | magnetic resonance imaging spectroscopy |
mRNA | messenger ribonucleic acid |
nd | no data available |
NMDA | glutamatergic N-methyl-D-aspartate |
NP | neuropathic pain |
NTG | nitroglycerine |
PDN | painful diabetic neuropathy |
PEA | palmitoylethanolamide |
PET | positron emission tomography |
PHN | postherpetic neuralgia |
RCT | randomized controlled trial |
SNP | single nucleotide polymorphism |
TCC | trigemino-cevical complex |
TNF | tumor necrosis factor |
Trp | tryptophan |
TRP | transient receptor potential |
TRPA | transient receptor potential ankyrin |
TRPC | transient receptor potential canonical |
TRPM | transient receptor potential melastatin |
TRPML | transient receptor potential mucolipin |
TRPP | transient receptor potential polycystin |
TRPV | transient receptor potential vanilloid |
TSPO | translocator protein |
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Migraine | Ref. | ||||
---|---|---|---|---|---|
EM | CM | ||||
M0 | MA | ||||
Ictally | Interictally | Ictally | Interictally | ||
↑plasma from external jugular vein | - | - | - | - | [41] |
↑plasma from cubital vein | - | - | - | - | [42] |
Neuropathic pain | ref. | ||||
Peripheral NP | Central NP | ||||
↑nerve fibers (painful neuroma) | - | [45] | |||
↑serum (CRPS) | - | [46] | |||
↑keratinocyta (PHN) | - | [47] |
Migraine | Ref. | |||||
---|---|---|---|---|---|---|
EM | CM | |||||
M0 | MA | |||||
Ictally | Interictally | Ictally | Interictally | |||
- | - | - | - | ↑TRPV-1-like immunoreactive nerve fibers density (the wall of scalp arteries) | [76] | |
Neuropathic pain | ref. | |||||
Peripheral NP | Central NP | |||||
↓pain intensity after 8% capsaicin patch treatment (in post-herpetic neuralgia, chronic postsurgical NP, post-traumatic NP, PDN, HIV-associated NP, painful radiculopathy, trigeminal neuralgia, chemotherapy-induced NP) | - | [20] [77] [78] [79] |
Migraine | Ref. | ||||
---|---|---|---|---|---|
EM | CM | ||||
M0 | MA | ||||
Ictally | Interictally | Ictally | Interictally | ||
- | ↑FAAH and AMT (platelet) (only in female patients) | - | - | - | [94] |
- | - | - | - | ↓anandamide (CSF) ↑PEA (CSF) | [95] |
- | - | - | - | ↓AMT, FAAH (platelet) | [96] |
- | - | - | - | ↓anandamide, 2-AG | [97] |
- | =anandamide (plasma) | - | =anandamide (plasma) | - | [98] |
Neuropathic pain | ref. | ||||
Peripheral NP | Central NP | ||||
- | =mean pain intensity after ultramicronized sublingually PEA treatment (NP associated with spinal cord injury) | [99] |
Migraine | Ref. | ||||
---|---|---|---|---|---|
EM | CM | ||||
M0 | MA | ||||
Ictally | Interictally | Ictally | Interictally | ||
↑glutamic acid (plasma) | ↑glutamic acid (plasma) | ↑glutamic acid (plasma) | ↑glutamic acid (plasma) | - | [118] |
- | - | ↑glutamic acid (platelet) | ↑glutamic acid (platelet) | - | [119] |
↓glutamic acid (plasma) | - | ↓glutamic (plasma) | - | - | [120] |
↑glutamic acid (CSF) | - | ↑glutamic acid (CSF) | - | - | [120] |
- | ↑glutamic acid (saliva) | - | - | - | [121] |
- | - | - | - | ↑glutamic acid (CSF) | [122] |
- | - | - | - | ↓KYNA (serum) | [123] |
- | ↓L-KYN, KYNA, anthranilic acid, picolinic acid, 5-hydroxy-indoleaceticacid (plasma) | - | - | - | [124] |
Neuropathic pain | ref. | ||||
Peripheral NP | Central NP | ||||
↑L-glutamate (plasma) in CRPS ↓L-Trp (plasma) in CRPS ↑the KYN/TRP ratio | - | [125] | |||
negative correlation: TRP serum level and pain intensity positive correlation: (the KYN/Trp ratio and pain intensity(temporomandibular disorders myalgia) | - | [126] |
Migraine | Ref. | ||||
---|---|---|---|---|---|
EM | CM | ||||
M0 | MA | ||||
Ictally | Interictally | Ictally | Interictally | ||
↑IL-6 (urine) =IL-1beta (urine) ↓TNF-alpha (urine) | ↑IL-6 (urine) =IL-1beta (urine) ↓TNF-alpha (urine) | - | - | - | [158] |
=IL-1, TNF (plasma) | =IL-1, TNF (plasma) | =IL-1, TNF (plasma) | =IL-1, TNF (plasma) | - | [159] |
- | =TNF-alpha, IL-6 (serum) | - | =TNF-alpha, IL-6 (serum) | - | [160] |
- | ↑TNF-alpha, IL-1beta, IL-10 (plasma) | - | - | - | [160] |
↑TNF-alpha (serum) | - | - | - | - | [161] |
↑IL-10, IL-6 (serum) | - | - | - | - | [162] |
↑IL-1 receptor antagonist (CSF) | - | ↑IL-1 receptor antagonist (CSF) | - | - | [161] |
=TN-Falpha (serum) | - | - | - | - | [163] |
↑IL-1beta, IL-6 (serum) ↑Il-10 (serum) | - | - | - | - | [164] |
↑IL-6 (serum) | - | ↑IL-6 (serum) | - | - | [165] |
↑TN-Falpha, IL-1beta, IL-6 (serum) | - | - | - | - | [166] |
- | ↓IL-6 (mRNA and serum) | - | - | - | [167] |
- | - | - | - | ↑TNF-alpha, IL-6 (serum) | [168] |
- | ↑IL-1beta (saliva) | - | - | - | [169] |
↑IL-18 (serum) | ↑IL-18 (serum) | ↑IL-18 (serum) | ↑IL-18 (serum) | - | [170] |
- | - | - | ↑IL-6 (mRNA) | - | [171] |
- | ↑IL-4, IL-18, TGF-beta, TNF-alpha (mRNA) =IL-1beta, IL-17, IL-2 (mRNA) | - | ↑IL-4, IL-18, TGF-beta, TNF-alpha (mRNA) =IL-1beta, IL-17, IL-2 (mRNA) | - | [172] |
Neuropathic pain | ref. | ||||
Peripheral NP | Central NP | ||||
↑TNF-alpha expression (Schwann cells) | - | [173] | |||
↑IL-2, TNF-alpha (mRNA, plasma) ↓IL-4, IL-10 (mRNA, plasma) | - | [174] | |||
↑TNF-alpha (serum) in PDN | - | [175] | |||
↑TNF-alpha (plasma) in PDN | - | [176] | |||
↑IL-6 (serum) in painful DSPN | - | [177] | |||
↑TNF-alpha, IL-1beta (mRNA) ↓IL-10 (mRNA) =IL-4 (mRNA) (in NP after peripheral nerve lesion) | - | [16] |
Migraine | Ref. | ||||
---|---|---|---|---|---|
EM | CM | ||||
M0 | MA | ||||
Ictally | Interictally | Ictally | Interictally | ||
↑S100B (serum) | ↑S100B (serum) | - | - | - | [199] |
↑S100B (serum) | ↑S100B (serum) | - | - | - | [24] |
- | ↓S100B (serum) | - | ↓S100B (serum) | - | [200] |
- | ↑S100B (serum) | - | - | ↑S100B (serum) | [202] |
- | ↑S100B (serum) | - | - | ↑S100B (serum) | [203] |
Neuropathic pain | ref. | ||||
Peripheral NP | Central NP | ||||
activated glial cells (PET):thalamus, anterior and posterior central gyrus, paracentral lobule | - | [9,204] |
Potential Targets | Comments |
---|---|
Calcitonin gene-related peptide (CGRP) | More studies on CGRP modulators in the subtypes are required. |
Transient receptor potential (TRP) ion channels | Better understanding of TRPs in the pathogenesis and discovery of more TRP modulators is expected. |
Endocannabinoid system | Characterizing the endocannabinoids system network, and the discovery of more enzyme modulators and of the potential use of the metabolites may help advance this field of research. |
Tryptophan-kynurenine (KYN) metabolic system | More studies on the status of various KYN metabolites in reference to glutamate levels are expected. |
Neuroinflammation | A consensus regarding the type of cytokines and sampling tissues that should be used to monitor an inflammatory status contributing to the pathogenesis should be attained. |
Microglia | The discovery of more biomarkers and imaging techniques to monitor the status of glial functions are expected. |
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Tajti, J.; Szok, D.; Csáti, A.; Szabó, Á.; Tanaka, M.; Vécsei, L. Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain. Int. J. Mol. Sci. 2023, 24, 4114. https://doi.org/10.3390/ijms24044114
Tajti J, Szok D, Csáti A, Szabó Á, Tanaka M, Vécsei L. Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain. International Journal of Molecular Sciences. 2023; 24(4):4114. https://doi.org/10.3390/ijms24044114
Chicago/Turabian StyleTajti, János, Délia Szok, Anett Csáti, Ágnes Szabó, Masaru Tanaka, and László Vécsei. 2023. "Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain" International Journal of Molecular Sciences 24, no. 4: 4114. https://doi.org/10.3390/ijms24044114