neurogenic inflammation
{{Short description|Type of inflammation}}
{{Technical|date=April 2024}}
Neurogenic inflammation is inflammation arising from the local release by afferent neurons of inflammatory mediators such as substance P, calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and endothelin-3 (ET-3).{{cite journal | vauthors = Peroutka SJ | title = Neurogenic inflammation and migraine: implications for the therapeutics | journal = Mol. Interv. | volume = 5 | issue = 5 | pages = 304–11 | date = October 2005 | pmid = 16249526 | doi = 10.1124/mi.5.5.10 }}{{cite journal | vauthors = Chen Y, Lyga J | title = Brain-skin connection: stress, inflammation and skin aging | journal = Inflamm Allergy Drug Targets | volume = 13 | issue = 3 | pages = 177–90 | date = 2014 | pmid = 24853682 | pmc = 4082169 | doi = 10.2174/1871528113666140522104422 }}{{cite journal | vauthors = Geppetti P, Nassini R, Materazzi S, Benemei S | title = The concept of neurogenic inflammation | journal = BJU Int. | volume = 101 | pages = 2–6 | date = March 2008 | issue = Suppl 3 | pmid = 18307678 | doi = 10.1111/j.1464-410X.2008.07493.x | s2cid = 1096295 | doi-access = }} In such neurons, the release of these pro-inflammatory mediators is thought to be triggered by the activation of ion channels that are the principal detectors of noxious environmental stimuli. In particular, the heat/capsaicin receptor TRPV1{{Cite journal|last1=Caterina|first1=M. J.|last2=Leffler|first2=A.|last3=Malmberg|first3=A. B.|last4=Martin|first4=W. J.|last5=Trafton|first5=J.|last6=Petersen-Zeitz|first6=K. R.|last7=Koltzenburg|first7=M.|last8=Basbaum|first8=A. I.|last9=Julius|first9=D.|date=2000-04-14|title=Impaired nociception and pain sensation in mice lacking the capsaicin receptor|journal=Science|volume=288|issue=5464|pages=306–313|doi=10.1126/science.288.5464.306|issn=0036-8075|pmid=10764638|bibcode=2000Sci...288..306C}} and the wasabi receptor TRPA1.{{Cite journal|last1=Lin King|first1=John V.|last2=Emrick|first2=Joshua J.|last3=Kelly|first3=Mark J. S.|last4=Herzig|first4=Volker|last5=King|first5=Glenn F.|last6=Medzihradszky|first6=Katalin F.|last7=Julius|first7=David|date=2019-09-05|title=A Cell-Penetrating Scorpion Toxin Enables Mode-Specific Modulation of TRPA1 and Pain|journal=Cell|volume=178|issue=6|pages=1362–1374.e16|doi=10.1016/j.cell.2019.07.014|issn=1097-4172|pmc=6731142|pmid=31447178}}{{Cite journal|last1=Zhao|first1=Jianhua|last2=King|first2=John V. Lin|last3=Cheng|first3=Yifan|last4=Julius|first4=David|date=2019-12-27|title=Mechanisms governing irritant-evoked activation and calcium modulation of TRPA1|url=https://www.biorxiv.org/content/10.1101/2019.12.26.888982v1|journal=bioRxiv|language=en|pages=2019.12.26.888982|doi=10.1101/2019.12.26.888982|doi-access=free}}{{Cite journal|last1=Zhao|first1=Jianhua|last2=Lin King|first2=John V.|last3=Paulsen|first3=Candice E.|last4=Cheng|first4=Yifan|last5=Julius|first5=David|date=2020-07-08|title=Irritant-evoked activation and calcium modulation of the TRPA1 receptor|url= |journal=Nature|volume=585|issue=7823|pages=141–145|language=en|doi=10.1038/s41586-020-2480-9|pmid=32641835|pmc=7483980|bibcode=2020Natur.585..141Z|issn=0028-0836}} TRPA1 channels stimulated by lipopolysaccharides may also cause acute neurogenic inflammation.{{cite journal | vauthors = Meseguer V, Alpizar YA, Luis E, Tajada S, Denlinger B, Fajardo O, Manenschijn JA, Fernández-Peña C, Talavera A, Kichko T, Navia B, Sánchez A, Señarís R, Reeh P, Pérez-García MT, López-López JR, Voets T, Belmonte C, Talavera K, Viana F |display-authors = 6| title = TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins | journal = Nat Commun | volume = 5 | pages = 3125 | date = 2014 | pmid = 24445575 | pmc = 3905718 | doi = 10.1038/ncomms4125 |bibcode = 2014NatCo...5.3125M}} Once released, these neuropeptides induce the release of histamine from nearby mast cells. In turn, histamine evokes the release of substance P and CGRP; thus, a bidirectional link between histamine and neuropeptides in neurogenic inflammation is established.{{cite journal | vauthors = Rosa AC, Fantozzi R | title = The role of histamine in neurogenic inflammation | journal = Br. J. Pharmacol. | volume = 170 | issue = 1 | pages = 38–45 | date = September 2013 | pmid = 23734637 | doi = 10.1111/bph.12266 | pmc = 3764847 }}
Neurogenic inflammation appears to play a role in the pathogenesis of numerous disorders, including migraine,{{cite journal | vauthors = Malhotra R | title = Understanding migraine: Potential role of neurogenic inflammation | journal = Ann Indian Acad Neurol | volume = 19 | issue = 2 | pages = 175–82 | date = 2016 | pmid = 27293326 | pmc = 4888678 | doi = 10.4103/0972-2327.182302 | doi-access = free }}{{cite journal | vauthors = Frediani F, Villani V, Casucci G | title = Peripheral mechanism of action of antimigraine prophylactic drugs | journal = Neurol. Sci. | volume = 29 | pages = S127–30 | date = May 2008 | issue = Suppl 1 | pmid = 18545913 | doi = 10.1007/s10072-008-0903-8 | s2cid = 24156261 }}{{cite journal | vauthors = Geppetti P, Capone JG, Trevisani M, Nicoletti P, Zagli G, Tola MR | title = CGRP and migraine: neurogenic inflammation revisited | journal = J Headache Pain | volume = 6 | issue = 2 | pages = 61–70 | date = April 2005 | pmid = 16362644 | pmc = 3452316 | doi = 10.1007/s10194-005-0153-6 }} psoriasis,Schön and Boehncke, [http://content.nejm.org/cgi/content/full/352/18/1899 Psoriasis: Neurogenic inflammation and other mechanisms] NEJM 352:1899-1912, Number 18, 2005{{cite journal | vauthors = Saraceno R, Kleyn CE, Terenghi G, Griffiths CE | title = The role of neuropeptides in psoriasis | journal = Br. J. Dermatol. | volume = 155 | issue = 5 | pages = 876–82 | date = November 2006 | pmid = 17034513 | doi = 10.1111/j.1365-2133.2006.07518.x | s2cid = 9257957 }} asthma,{{cite journal | vauthors = Verones B, Oortgiesen M | title = Neurogenic inflammation and particulate matter (PM) air pollutants | journal = Neurotoxicology | volume = 22 | issue = 6 | pages = 795–810 | date = December 2001 | pmid = 11829413 | doi = 10.1016/S0161-813X(01)00062-6 | url = https://zenodo.org/record/1259847 }} vasomotor rhinitis,{{cite journal | vauthors = Knipping S, Holzhausen HJ, Riederer A, Schrom T | title = [Ultrastructural changes in allergic rhinitis vs. idiopathic rhinitis] | language = de | journal = HNO | volume = 56 | issue = 8 | pages = 799–807 | date = August 2008 | pmid = 18651116 | doi = 10.1007/s00106-008-1764-4 | s2cid = 24135943 }} fibromyalgia, eczema, rosacea, dystonia, and multiple chemical sensitivity.
EcopsychologyVol. 9, No. 2 Published Online:1 Jun 2017 https://doi.org/10.1089/eco.2016.0045{{cite journal | vauthors = Orriols R, Costa R, Cuberas G, Jacas C, Castell J, Sunyer J | title = Brain dysfunction in multiple chemical sensitivity | journal = J. Neurol. Sci. | volume = 287 | issue = 1–2 | pages = 72–8 | date = December 2009 | pmid = 19801154 | doi = 10.1016/j.jns.2009.09.003 | s2cid = 28255407 }}{{cite journal | vauthors = Bascom R, Meggs WJ, Frampton M, Hudnell K, Killburn K, Kobal G, Medinsky M, Rea W | title = Neurogenic inflammation: with additional discussion of central and perceptual integration of nonneurogenic inflammation | journal = Environ. Health Perspect. | volume = 105 | pages = 531–7 | date = March 1997 | issue = Suppl 2 | pmid = 9167992 | pmc = 1469802 | doi = 10.1289/ehp.97105s2531 }}
In migraine, stimulation of the trigeminal nerve causes neurogenic inflammation via the release of neuropeptides, including substance P, nitric oxide, vasoactive intestinal polypeptide, 5-HT, neurokinin A, and CGRP.{{cite journal | vauthors = Kalra AA, Elliott D | title = Acute migraine: Current treatment and emerging therapies | journal = Ther Clin Risk Manag | volume = 3 | issue = 3 | pages = 449–59 | date = June 2007 | pmid = 18488069 | pmc = 2386351 }}{{cite journal | vauthors = Link AS, Kuris A, Edvinsson L | title = Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system | journal = J Headache Pain | volume = 9 | issue = 1 | pages = 5–12 | date = February 2008 | pmid = 18217201 | pmc = 2245994 | doi = 10.1007/s10194-008-0011-4 }}{{cite journal|last1=Grossmann, MD|first1=Werner|last2=Schmidramsl, MD|first2=Hanns|title=An Extract of Petasites hybridus Is Effective in the Prophylaxis of Migraine|journal=Alternative Medicine Review|date=2001|volume=6|issue=3|pages=303–10|url=http://www.altmedrev.com/publications/6/3/303.pdf|access-date=14 June 2015|pmid=11410074}}
Prevention
Magnesium deficiency causes neurogenic inflammation in a rat model. Researchers have theorized that since substance P which appears at day five of induced magnesium deficiency, is known to stimulate in turn the production of other inflammatory cytokines including IL-1, Interleukin 6 (IL-6), and TNF-alpha (TNFα), which begin a sharp rise at day 12, substance P is a key in the path from magnesium deficiency to the subsequent cascade of neuro-inflammation.{{cite journal | vauthors = Weglicki WB, Phillips TM | title = Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis | journal = Am. J. Physiol. | volume = 263 | issue = 3 Pt 2 | pages = R734–7 | date = September 1992 | pmid = 1384353 | doi = 10.1152/ajpregu.1992.263.3.R734 }} In a later study, researchers provided rats dietary levels of magnesium that were reduced but still within the range of dietary intake found in the human population, and observed an increase in substance P, TNF alpha (TNFα) and Interleukin-1 beta (IL-1β), followed by exacerbated bone loss. These and other data suggest that deficient dietary magnesium intake, even at levels not uncommon in humans, may trigger neurogenic inflammation and lead to an increased risk of osteoporosis.{{cite journal | vauthors = Rude RK, Singer FR, Gruber HE | title = Skeletal and hormonal effects of magnesium deficiency | journal = J Am Coll Nutr | volume = 28 | issue = 2 | pages = 131–41 | date = April 2009 | pmid = 19828898 | doi = 10.1080/07315724.2009.10719764 | s2cid = 43556609 }}
Treatment
In 2018, three CGRP blockers were approved by the FDA for the prevention of migraine: erenumab; fremanezumab; and galcanezumab.
:The calcitonin gene-related peptide (CGRP) is a therapeutic target in migraine because of its hypothesized role in mediating trigeminovascular pain transmission and the vasodilatory component of neurogenic inflammation (see "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Role of calcitonin gene-related peptide'). In 2018, the US Food and Drug Administration (FDA) approved the CGRP antagonists erenumab [36], fremanezumab [37], and galcanezumab [38] for migraine prevention.
:Smith, "Preventive treatment of migraine in adults" UpToDate 2019{{Cite web|url=https://www.uptodate.com/contents/preventive-treatment-of-migraine-in-adults?search=migraine%20treatment§ionRank=1&usage_type=default&anchor=H382445576&source=machineLearning&selectedTitle=2~150&display_rank=2#H382445576|title = UpToDate}}
Additional CGRP blockers are progressing through clinical trials.[https://migraine.com/news/cgrp-race The Race to Offer CGRP for Migraine] Migraine.com Editorial Team July 21, 2017
Anticipating later botox therapy for migraine, early work by Jancsó et al. found some success in treatment using denervation or pretreatment with capsaicin to prevent uncomfortable symptoms of neurogenic inflammation.{{cite journal | vauthors = Jancsó N, Jancsó-Gábor A, Szolcsányi J | title = Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin | journal = Br J Pharmacol Chemother | volume = 31 | issue = 1 | pages = 138–51 | date = September 1967 | pmid = 6055248 | pmc = 1557289 | doi = 10.1111/j.1476-5381.1967.tb01984.x }}
A 2010 study of the treatment of migraine with CGRP blockers had shown promise for CGRP blockers.{{cite journal | vauthors = Durham PL, Vause CV | title = Calcitonin gene-related peptide (CGRP) receptor antagonists in the treatment of migraine | journal = CNS Drugs | volume = 24 | issue = 7 | pages = 539–48 | date = July 2010 | pmid = 20433208 | pmc = 3138175 | doi = 10.2165/11534920-000000000-00000 }} In early trials, the first oral nonpeptide CGRP antagonist, MK-0974 (Telcagepant), was shown effective in the treatment of migraine attacks,{{cite journal | vauthors = Farinelli I, Missori S, Martelletti P | title = Proinflammatory mediators and migraine pathogenesis: moving towards CGRP as a target for a novel therapeutic class | journal = Expert Rev Neurother | volume = 8 | issue = 9 | pages = 1347–54 | date = September 2008 | pmid = 18759547 | doi = 10.1586/14737175.8.9.1347 | s2cid = 207195138 }} but elevated liver enzymes in two participants were found. Other therapies and other links in the neurogenic inflammatory pathway for interruption of disease are under study, including migraine therapies.{{cite journal | vauthors = Farinelli I, De Filippis S, Coloprisco G, Missori S, Martelletti P | title = Future drugs for migraine | journal = Intern Emerg Med | volume = 4 | issue = 5 | pages = 367–73 | date = October 2009 | pmid = 19551474 | doi = 10.1007/s11739-009-0273-0 | s2cid = 26070466 }}
Noting that botulinum toxin has been shown to have an effect on inhibiting neurogenic inflammation, and evidence suggesting the role of neurogenic inflammation in the pathogenesis of psoriasis, the University of Minnesota has a pilot clinical trial underway to follow up on the observation that patients treated with botulinum toxin for dystonia had dramatic improvement in psoriasis.{{ClinicalTrialsGov|NCT00816517|Use of Botulinum Toxin to Treat Psoriasis}}
Astelin (Azelastine) "is indicated for symptomatic treatment of vasomotor rhinitis including rhinorrhea, nasal congestion, and post nasal drip in adults and children 12 years of age and older."Product Information: Astelin, azelastine. Wallace Laboratories, Cranbury, NJ. (PI Revised 08/2000) PI Reviewed 01/2001{{cite journal | vauthors = Gehanno P, Deschamps E, Garay E, Baehre M, Garay RP | title = Vasomotor rhinitis: clinical efficacy of azelastine nasal spray in comparison with placebo | journal = ORL J. Otorhinolaryngol. Relat. Spec. | volume = 63 | issue = 2 | pages = 76–81 | date = 2001 | pmid = 11244365 | doi = 10.1159/000055714 | s2cid = 23292869 }}
Statins appear to "decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons,"{{cite journal | vauthors = Bucelli RC, Gonsiorek EA, Kim WY, Bruun D, Rabin RA, Higgins D, Lein PJ | title = Statins decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons | journal = J. Pharmacol. Exp. Ther. | volume = 324 | issue = 3 | pages = 1172–80 | date = March 2008 | pmid = 18079356 | doi = 10.1124/jpet.107.132795 | s2cid = 1001915 }} and so might be of use in treating diseases presenting with predominant neurogenic inflammation.
Research
In a 2012 article{{cite journal | vauthors = Chiu IM, von Hehn CA, Woolf CJ | title = Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology | journal = Nat. Neurosci. | volume = 15 | issue = 8 | pages = 1063–7 | date = July 2012 | pmid = 22837035 | pmc = 3520068 | doi = 10.1038/nn.3144 }} in Nature Neuroscience Chiu et al. discuss the development of science related to neurogenic inflammation and provide a graphic{{cite journal | pmc=3520068 | pmid=22837035 | doi=10.1038/nn.3144 | volume=15 | title=Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology |vauthors=Chiu IM, von Hehn CA, Woolf CJ | journal=Nat Neurosci | issue=8 | at=[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520068/figure/F3/ Figure 3]| year=2012 }} illustrating key discoveries leading toward the current understanding of neurogenic inflammation, its mechanisms, and the conditions caused by its disorder.
References
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External links
- [https://web.archive.org/web/20110719143654/http://www.asthma.ge/neurogenic.htm Bronchial asthma and other neurogenic diseases: migraine, trigeminal neuralgia and epilepsy]
- Schön and Boehncke, [http://content.nejm.org/cgi/content/full/352/18/1899 Psoriasis: Neurogenic inflammation and other mechanisms] NEJM 352:1899–1912, Number 18, 2005