Airway Genetics and Ambient Combustion Aerosol

SPC 11 Central Sensitization: Intense, Repeated, and Sustained Inputs

SPC 11 Central Sensitization: Intense, Repeated, and Sustained Inputs

Links: 35 CAR Test SPC Questions
CAR Warm Up
SPC 1 Introduction: South Pole CAR (SPC) - A Character Test
SPC 2 South Pole CAR: ACA PM, Band Cell, and Monocyte Drop
SPC 3 ACA PM and ME/CFS: Do We Hear An Echo?
SPC 4 ACA UFPM: In the RBC - Through the BBB
SPC 5 ACA UFPM: IL-1 beta, RBC, BBB, - MCS and ME/CFS
SPC 6 ACA UFPM: Nerve Penetration
SPC 7 ACA UFPM: Olfactory, BBB, AD, PD, MCS, and ME/CFS
SPC 8 ACA PM: Gastro-Inflammation, Immunity, Vagal Circuitry
SPC 9 Veronesi: Sensory Nerve Insight
SPC 10 Kimata: Histamine Warning - Return to Masking
SPC 11 Central Sensitization: Intense, Repeated, and Sustained Inputs

On CAR
SPC 12 Disease Conditions Begin: Airway Epithelial Injury
SPC 13 Exposed Sensory Nerves - TRPA1
SPC 14 Exposed TRPA1: Central Sensitization
SPC 15 ACA: Loud and Clear
SPC 16 Airway Cytokine Release: Principle Mediator of Systemic Inflammation
SPC 17 Calderon-Garciduenas: Airway to Systemic: Putting It Together
SPC 18 Airway Gaps - Exposed Nerves - UFPM to the CNS
SPC 19 ACA PM: Months and Years Residence Time
SPC 20 Airway Gaps: Reduced Detox Enzyme Intervention
SPC 21 Solvents and Pesticides Primary: Shoe Fits Glove?
SPC 22 Veronesi and Roy: Genetic Difference in Airway Sensitivity

SPC 23 Jung Was Right Sort Of
SPC 24 Veronesi and Jung: A Perfect Match
SPC 25 Tailpipe and Chimney Emissions: Horizontal Coning
SPC 26 How Far Symptoms Travel: 25 Years, 500 Locations, 22 States
SPC 27 Not Into That Kind of Entertaining
SPC 28 Does it Cost More Than Money?
SPC 29 Airway to Systemic: Dysfunction of Detox Enzymes - Terlecky
SPC 30 Airway to systemic: Dysfunction of Detox Enzymes - Khatsenko
SPC 31 Gerde and Stadler: Benzo[a]pyrene Forever?
SPC 32 Phase I and II Detox Enzymes Defined

Lifestyle Change
SPC 33 ACA Catastrophic Consequences
SPC 34 Impossibly Good City Design
SPC 35 South Pole CAR Test: Satisfaction Guarantee

MCS 3 Definition and Concensus Criteria

MCS 3a Criteria Amendment Research Points (CAR)

MCS 3aa Etiology: Concensus Author CAR Test (SPC)

MCS 3b CAR References

SPC 11 Central Sensitization: Intense, Repeated, and Sustained Inputs

Please choose the Incorrect Statement

SPC 11a)

MERCK 1999:
"...A nerve cell (neuron) has two major functions: propagation of an action potential (nerve impulse, signal) along its axon and transmission of this signal from one neuron to another neuron, or to an effector cell to elicit a response...
...Impulse conduction along an axon is electrical, caused by the exchanges of Na+ and K+ ions across the neuronal membrane. In contrast, impulse transmission from one neuron to another neuron or to a non-neuronal effector cell depends on the action of specific neurotransmitters on specific receptors...
...Synapses occur between neuron and neuron and, in the periphery, between neuron and effector...in the CNS more complex arrangements exist...

...The nerve cell body produces enzymes that are involved in the synthesis of most transmitters. The enzymes act on precursor molecules taken up by the neuron to form the neurotransmitter. The neurotransmitter is stored at the nerve terminal in vesicles...
...An action potential arriving at the terminal can activate calcium currents and precipitate the simultaneous release of neurotransmitter molecules from many vesicles by fusing the membrane of the vesicles to that of the nerve terminal. An opening forms through which the molecules are expelled into the synaptic cleft by exocytosis...
...Neurotransmitters diffuse across the synaptic cleft, bind briefly to receptors, and activate them, causing physiologic responses. Depending on the receptor, the response may be excitatory (ie, initiating a new action potential) or inhibitory (ie, inhibiting the development of a new action potential)...

...A neurotransmitter is a chemical that is selectively released from a nerve terminal by an action potential, interacts with a specific receptor on an adjacent structure, and, if received in adequate amounts, elicits a specific physiologic response...
...Neurotransmitter receptors are protein complexes that span the cell membrane..."

SPC 11b)

LATREMOLIERE 2009:

"...central sensitization...activity or use dependent form of functional synaptic plasticity that resulted in pain hypersensitivity...triggered by the activity evoked in dorsal horn neurons by input from c-nociceptors...chemical activation of nociceptors by irritant compounds...the TRPA1 channel...TRPV1 channel..."

SPC 11c)

TODD 2010:

"...Dorsal horn neurons receive sensory information from primary afferents...The incoming information is processed by complex circuits involving excitatory and inhibitory interneurons, and transmitted to projection neurons for relay to several brain areas...nociceptive information is conveyed to the ventral horn and contributes to spinally-mediated nocifensive reflexes. Activity at various points in these circuits can be modulated by axons that descend from the brainstem..."

SPC 11d)

LATREMOLIERE 2009:

"...The key features of acute activity-dependent central sensitization are that it is induced with a short latency (seconds) by intense, repeated, or sustained nociceptor inputs and typically lasts for tens of minutes to several hours in the absence of further nociceptor input..."

...It generally requires activation of NMDA receptors for its induction, and these receptors contribute to its maintenance. Nevertheless, as reviewed above, multiple different triggers can contribute to the establishment of this form of central sensitization: glutamate acting on NMDAR, but also on AMPAR and mGluR, the neuropeptides substance P and CGRP, the kinin bradykinin, as well as BDNF and NO...

...the essence of central sensitization is a constantly changing mosaic of alterations in membrane excitability, reductions in inhibitory transmission, and increases in synaptic efficacy, mediated by many converging and diverging molecular players on a background of phenotypic switches and structural alterations..."

SPC 11e)

ORRIOLS 2009:
"...MCS patients present brain signal photon emission computed tomography (SPECT) and psychometric scale changes...
...In comparison to controls, cases presented basal brain SPECT hypoperfusion in small cortical areas of the right parietal and both temporal and fronto-orbital lobes. After chemical challenge, cases showed hypoperfusion in the olfactory, right and left hippocampus, right parahippocampus, right amygdala, right thalamus, right and left Rolandic and right temporal cortex regions (p<0.01)...

...Our study showed brain SPECT dysfunction, particularly in those areas involved in odor processing...the pathway that joins the olfactory region to the orbito-frontal cortex through the thalamus is considered to be a control area of olfactory stimuli (Guyton 2000)...The olfactory region is also connected to the limbic system, a highly sensitizable area, which is responsible for vegetative responses and some emotions related to smell (Guyton 2000)...

...Neurologic transmission is a selective process in which excitatory and inhibitory signals control the final information transmitted, inhibitory signals help stabilize nervous system function and prevent excessive intensity and spread of neurologic circuits. Thus, reduced activity of inhibitory neurologic mechanisms can produce much greater excitability and facilitation of nerve stimuli, even in apparently unrelated areas...

...Neurologic dysfunction observed prior to chemical exposure could point to persistent subclinical neurologic changes. In fact, basal SPECT brain cortical hypoactivity was found in our patients. In animal models, inflammation and permanent damage of the olfactory neuronal pathways could result from translocation of inhaled ultrafine particles to the brain (Elder 2006)..."

SPC 11f)

CALDERON-GARCIDUENAS 2008:
"...Breakdown of the nasal barrier in pollution-exposed subjects may also contribute to brain inflammation by increasing the access of PM to the brain through the olfactory and trigeminal pathways. The finding of PM in the glomerular region of the OBs of MC residents indicates that particles are readily transported from the nasal cavity to the brain via the olfactory nerve... a pathway very well known in experimental animals exposed to metals (Dorman 2002, Henriksson 1997). Moreover, there is an early and significant upregulation of COX2, Il-1beta, and CD 14 in the OB, which is indicative of an ongoing inflammatory process...

...Given that axons from the olfactory neurons project to the OB, and the primary axons of the projection neurons send off collateral branches to the olfactory nuclei, piriform cortex, entorhinal cortex, and amygdaloid nuclei, and then to the hippocampal formation and the parahippocampal gyrus, it is expected that significant inflammatory process in the OB in these highly exposed subjects may translate into olfactory dysfunction, which is indeed the case in young adults...Olfactory dysfunction is an early clinical finding in several neurodegenerative disorders, including Alzheimer and Parkinson's diseases (Hawkes 2003)..."

SPC 11g)

SPECT hypoactivity, permanent damage to the olfactory neuronal pathways, and central sensitization in MCS patients can't be caused by the inflammatory process of translocated ultrafine particles to the brain or intense, repeated, and sustained input from exposed sensory nerves in damaged airway epithelium - alterations in membrane excitability, reductions of inhibitory transmission, and increases in synaptic efficacy.

Lifestyle Change
SPC 33 ACA Catastrophic Consequences
SPC 34 Impossibly Good City Design
SPC 35 South Pole CAR Test: Satisfaction Guarantee

MCS 3 Definition and Concensus Criteria

MCS 3a Criteria Amendment Research Points (CAR)

MCS 3aa Etiology: Concensus Author CAR Test (SPC)

MCS 3b CAR References

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SPC 11 Central Sensitization: Intense, Repeated, and Sustained Inputs

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