HOW the P terygo - P alatine G anglion matters in… BIPOLARITY too G. T reviranus, B erne

1. 12thInternational Review of AChvia M2 inflames BBB BIPOLAR DISORDER MC byCGRP PACAP Nice, 22.May 2012 3rd S1 INS PACAP 1st  ICA miniG TGG ? HOW theP terygo- P alatineG anglionmattersin… BIPOLARITYtooG.Treviranus, Berne Noseda 2010 Major part No CGRP ! 1893 Sp5C V1 PPG Beckers 1991 SSN roseodor  brainstem IN MIG attack SSN-“TG-CERVICAL-complex” 2nd May 2009 GM  metaAn HYSTERIA?W.Fliess & S.Freud ? Retrograde INFL TNF-a 0,1 mm TENS CH MIG: 1894 Fasmer NO ACh VIPPACAPOUTPUT STIMULATEPPG & HEAL Cluster Headache CR 61%, PR 16%, NR 23% withinminutes! OPEN BBB BLOCKPPG &  STOP HEADPAIN, C2-C3, asthma,(LBP etc.) NOT allodyniain MIG 1: 1st outputCGRP, PACAP, SP MastCell(CGRP-R+)Lennerz 2008 MC degranulationTheoharides 20052: NO DURA CGRP-receptors NO AXON-REFLEX forTG «Brainstemdisorder» SPOT PPG Non –B~stem ARTERIES TG FACIAL V1,2 PPG  eye, PPG ? BBB biposuisseinstituteberne Hysteria & Headache MC 1

2. The Naso-genital Link to... Mast cells PNS / CNS Mast Cells  FEMALE & MCs 1: ablationof PPGs in ratscausespseudopregnancy 2: estrus (E2 max) MC cycle anogenitalerogenicareasof VPL thalami? fromdura 3: Ovulation=dangersignal IR. Polycysticor post-MP ovariesMCs 4: doves:  MC in med. habenula courtshipandparenthood. 5: PNS-nerve ligation MC thalamus MC in Defense: ++ brainfunction avoidancecleaningbhv ++Allergicpreventive ++AntiMicrobial Peptides + «suicidal»extra-cellularfibrin traps againstgerms ? WMHI BUILD VESSELS (VEGF) Brain MAST cellsCLOSE TO N~s & Art. 3% MIGRATE VARIATEspecies, area, eco ACTIVE SP, NGF ,E2 DEGRAN’ PACAP, CGRP, etc.  GFs (NGF…), serineproteasee, iNOS, cytokines (TNFa), heparin, histamine, tryptase, 5-H.T, etc. MC in psychiatry: • PAIN DISORDER • AUTISM? Theoharides 2011 2012 • BPAD ? • Borderline PD ? Yin & yangof MC in MS MALE & MCs 1:animal:intraspecies fights MCs med. habenulaattractedby NGF 2: BLOCKED MCsANX-likebhvrat biposuisse institute berne 2 Mast cells

3. PPG PACAP Putamen Only L Globus pallidus larger Kempton 2008 Headache ? MCA BP ?ACA-MCA-PCA Shape! Hwang (Seoul) no Li+2006Li+ + -  Search for ? repetitive BBB openingfactors w/ periarterialneurotrophicortoxiceffect Mast Cells? biposuisseinstituteberne 3 Posterior CA ! Arterialpathologyof BPAD

4. BPAD = MC-«GOUT retroceedingtothebrain» Bugs: bacteria fungi, (virus) Lesion Allergen Chemicals Heat, cold Co-occurrence OR (Arnold 2006) P(BP|FM+)/P(BP|FM-)=x135 P(UP|FM+)/P(UP|FM-)=x2.7 Most BP,UP  FM Insula S1 S2 3rd order Thalamus status NT p75 SNS  virus Sloan 2007 D6 Chemokine-scavenging Rec. LymphNODES:NGF Timidity, LT-defense, Lymphatic APC to Top- down 2nd order ascension MC DRG A-b A-d PAIN+ = TLR4 x HSp90 (?) Hutchinson 2009 LEFT axilla PNS 1st order Glu =< AMPA via the lymphatics? i.perit. MC activator rat  at spinal medulla to C2 for head pain at L6-L2 for visceral pain Small Slow C-Fiber “noceffectors” Dorsal Horn 4   wikipedia, lymphnotes.com & WebMD Scientific American® PICTORIAL SOURCES

5. W. Ren {Guangzhou}. Neuropsychopharmacology 2011; 36:979-2 injured PNS  TNFain brain TNFabyMCs? dampenedby PPG? • Spared-Nerve-Injuryr&m TNAa in inplasma -  in CSF in HIPPOCAMPUS WORKING-MEMORY TNFareleasedby MCs, gliaandneurons M2 ACh facilitatecognition M2 antagonistmethoctramineactivates MCs M2 k.o. mice : likeTNFaWORKING-MEMORY -  maybe M2-cholinergic outputof PPG dampensinflammatorymastcellactivity. «fibrofog» biposuisse institute berne 5

6. 12thInternational Review of BIPOLAR DISORDER Nice, 23.May 2012 VIP PACAP Master of N/Immune cellcrosstalk • VIP GABA VAthalamus MC releaseofNGF and repair & recoveryin Parkinson-rats Korkmaz 2010, 2012 • PACAP-38 >>VIP PLC Dural MC degranulationBaun 2012 • N~protectiveEAE (MS); auto-reactive Th1/Th17 • VIP  Microglia colitismice • Memory & learning • Blushingheat (Kellogg 2010) • VIP Serum  in Cluster headache biposuisse institute berne 6

7. Silvan Tomkins RguiltshameL gyrusrectus SHAME w/ BLUSH (PPG) :pervasive, also cognitive BRAKE ofexcess, esp. AGGRESSION with SUBMISSIVE dysplay in „neurotic“ CONSPECIFIC STRUGGLE  ISTDPNEUROSIS chron. defeated/-inginflamed immune systemcholerichierarchy,triggeredby «CLENCH, dont BITE»? PPG :: just vasodilation OR shame, dissociation, pain,? Nestor 2012 (Boston) Tangney (Fairfax) Habib Davanloo 42% CPS-likesymptoms DefineBlumer’s SUBICTAL DYSPHORIA in psychiatry … 31% Dietrich Blumer 5,6% 8,1%  age MDD motherORx4.9 50’s Adol’s SIDS 2nd same hit? AW-InfectPPGBBB dysmorphicbrainstem /caseinoMOentry + PPG Auton. brainstem biposuisse institute berne 7 Yarnitzki 2003

8. MCs need PKC & GSK3β TMX MC exocytosisstartswithCa2+-store openerI145P3 :: Ca2+ replenishedby SOCE e.g. TRPC3 byLI PKC bslacksthereins (MARCKS-ED) on I145P3furtherneeded(Gadi 11) – at least IF byIgE-on-FcεRI • IP3IMPase-(„on site II“)-inhibitor LI • MARCKS  LI, VPA(Watson 98) • PKC in Mania, sleep(-), AMPH; GWAS-BP: enz(PKC) – in Depression: pmort, modelPKC PKC-iso LI, VPA, x iso: a,e CNS !TMX a, bI, h, d, zbIbII (a, d) LI, VLPA, SGA NO conc. change but function(Pandev 02, 08)?g only CNS ! SRI x iso: g,d • GSK3β in MC essential 4: cytokineprod, chemoattraction, andsurvival :: GSK3β-inhibitors:LI etc. „theabilityofthe PFC toregulateemotion, thoughtandactionismarkedlyimpairedbyoveractivityof PKC “ Zarate Manji 2009 biposuisse institute berne 8

9. Questions … www.biposuisse.ch biposuisse@bluewin.ch biposuisse institute berne