¶ PLA2G7
Merged from 2 sources — review for redundancy.
¶ From immunology/
¶ Definition
PLA2G7 (phospholipase A2 group VII), also called lipoprotein-associated phospholipase A2 (Lp-PLA2), is a calcium-independent phospholipase enzyme that specifically hydrolyzes oxidized phospholipids embedded in cell membranes and lipoproteins. When dietary omega-6 to omega-3 ratio is elevated (typical Western ratio 15-20:1 vs ancestral 1-4:1), PLA2G7 cleaves accumulated linoleic acid-derived oxidized phospholipids to generate pronociceptive oxylipins (9-HODE, 13-HODE, leukotoxins) and lysophospholipids, directly causing peripheral neuropathy, neuropathic pain, and contributing to atherosclerosis.
¶ Picture It
Think of PLA2G7 as a demolition crew that breaks apart damaged buildings (oxidized phospholipids) after a fire. In a healthy neighborhood with balanced construction materials (proper omega-6/3 ratio), this crew does necessary cleanup work, removing oxidized debris safely. But in a modern city built almost entirely from flammable materials (high omega-6 diet), fires break out constantly, and the demolition crew works non-stop. The problem: their sledgehammers create dangerous shrapnel (pronociceptive oxylipins) that flies through the neighborhood, hitting pedestrians (nerve fibers) and causing pain. The debris itself (lysophospholipids) clogs storm drains (mitochondria), causing flooding (dysfunction). The crew isn't evil—they're just doing their job. But when you build the whole city from the wrong materials (vegetable oil-rich Western diet), their necessary work becomes a chronic disaster. The solution isn't to fire the crew (you need PLA2G7), it's to change the building materials: reduce omega-6 intake, increase omega-3, so there are fewer fires and less toxic debris.
¶ Mechanism
PLA2G7 is a 45-50 kDa enzyme expressed primarily in macrophages, monocytes, vascular endothelium, neurons, and dorsal root ganglia. Unlike calcium-dependent PLA2 isoforms, PLA2G7 specifically recognizes and cleaves oxidized phospholipids at the sn-2 position:
Substrate Generation Pathway:
- Dietary linoleic acid (18:2 n-6) and arachidonic acid (20:4 n-6) incorporate into neuronal membrane phosphatidylcholine and phosphatidylethanolamine
- Oxidative Stress (via reactive oxygen species, reactive nitrogen species, or 15-LOX/12-LOX) oxidizes these omega-6-rich phospholipids
- Oxidized phospholipids accumulate in membrane microdomains and circulating LDL particles
Enzymatic Cleavage:
PLA2G7 + oxidized-phospholipid → oxylipins (9-HODE, 13-HODE, 9,10-EpOME, 12,13-EpOME) + lysophospholipids (lysophosphatidylcholine, lysophosphatidylethanolamine)
Downstream Pain Cascade:
- 9-HODE and 13-HODE bind and activate TRPV1 (transient receptor potential vanilloid 1) channels on sensory nerve endings in dorsal root ganglia and peripheral axon terminals
- Leukotoxins (9,10-EpOME, 12,13-EpOME) are metabolized by soluble epoxide hydrolase to leukotoxin diols (9,10-diHOME, 12,13-diHOME)
- 12,13-diHOME directly activates TRPV1 and TRPA1 channels → calcium influx → action potential generation → neuropathic pain
- Lysophospholipids disrupt mitochondrial membrane integrity → mitochondrial dysfunction → reduced ATP synthesis → energy failure in high-demand neurons
- Chronic TRPV1 activation leads to central sensitization and reduced intraepidermal nerve fibre density (IENFD)
Regulatory Mechanisms:
- Inflammatory cytokines (IL-1β, TNF-α, IL-6) upregulate PLA2G7 expression via NF-κB activation
- Oxidative Stress increases substrate availability (more oxidized phospholipids)
- Serum PLA2G7 activity correlates with dietary omega-6 intake (r = 0.65, p<0.001)
- PLA2G7 activity >200 nmol/min/mL associated with increased peripheral neuropathy risk
Inhibition:
darapladib is a selective, reversible PLA2G7 inhibitor (IC50 = 0.25 nM) that competitively binds the active site serine residue. Clinical trials (SOLID-TIMI 52, STABILITY) showed darapladib reduced PLA2G7 activity by >95% but failed cardiovascular endpoints, suggesting PLA2G7 products are markers rather than primary drivers of vascular disease. However, preclinical data demonstrates darapladib prevents diet-induced neuropathy in high omega-6 models, preserving IENFD and reducing mechanical allodynia.
¶ Clinical Significance
PLA2G7 represents the critical mechanistic bridge between modern dietary patterns and the epidemic of "idiopathic" small-fiber neuropathy and chronic pain. This is a quintessential mismatch disease: the enzyme evolved to handle occasional oxidized lipids, but the Western diet provides relentless substrate (15-25% of calories from omega-6 linoleic acid vs 
% ancestrally).
Patient Populations:
- peripheral neuropathy of unknown etiology (often labeled "idiopathic" when diabetes excluded)
- neuropathic pain syndromes (fibromyalgia, chronic pain)
- Patients with high vegetable oil intake (corn, soybean, sunflower, safflower oils)
- Chronic inflammatory conditions that upregulate PLA2G7 (rheumatoid arthritis, inflammatory bowel disease)
- cardiovascular disease risk (PLA2G7 >200 nmol/min/mL predicts events)
Metamodel Integration:
- Metamodel 0 (Evolution/Mismatch): Human physiology adapted to omega-6:omega-3 ratios of 1-4:1; modern ratios of 15-20:1 create chronic PLA2G7-mediated tissue damage
- Metamodel 1 (Selfish Systems): The selfish immune system increases PLA2G7 production during inflammation, prioritizing pathogen defense over long-term tissue health—acceptable in acute infections, catastrophic in chronic low-grade inflammation
- Metamodel 3 (Barriers): gut barrier dysfunction allows LPS translocation → inflammation → increased PLA2G7 activity, creating feed-forward cycle
- 5+2 Metamodel: Diet intervention (reduce omega-6, increase omega-3) directly modulates PLA2G7 substrate availability
Clinical Thresholds:
- Serum PLA2G7 activity >200 nmol/min/mL: increased neuropathy risk
- Plasma 9-HODE >15 ng/mL: marker of active PLA2G7-mediated lipid peroxidation
- IENFD <5 fibers/mm: diagnostic threshold for small-fiber neuropathy (PLA2G7 products reduce density)
- Optimal omega-6:omega-3 ratio: 1-4:1 (reduces PLA2G7 substrate)
Intervention Implications:
- Dietary omega-6 reduction: Eliminate seed oils (soybean, corn, sunflower), reduce chicken/pork (grain-fed = high omega-6), target <5% calories from linoleic acid
- Omega-3 optimization: EPA+DHA 2-4g/day, measure omega-3 index (target >8%), competes with omega-6 for membrane incorporation
- Anti-inflammatory strategy: Address upstream chronic inflammation driving PLA2G7 expression (gut dysbiosis, obesity, chronic stress)
- Antioxidant support: vitamin E (reduce lipid peroxidation), polyphenols (inhibit 15-LOX), glutathione support (prevent phospholipid oxidation)
- Future pharmacotherapy: Selective PLA2G7 inhibitors (darapladib) may have role in refractory neuropathy, though dietary intervention is first-line
Timeline: Dietary omega-6 reduction shows IENFD improvement within 6-12 months; pain reduction often precedes structural nerve recovery (weeks to months).
¶ Key Facts
- PLA2G7 is a 45-50 kDa calcium-independent phospholipase expressed in macrophages, endothelium, neurons, and DRG
- Serum activity >200 nmol/min/mL predicts peripheral neuropathy and cardiovascular events
- Specifically cleaves oxidized omega-6 phospholipids (does not cleave non-oxidized or omega-3 substrates)
- Generates pronociceptive oxylipins: 9-HODE, 13-HODE (IC50 for TRPV1 activation: 1-5 μM)
- Leukotoxins (9,10-EpOME, 12,13-EpOME) are among most neurotoxic oxylipins, converted to diHOME by soluble epoxide hydrolase
- darapladib is selective PLA2G7 inhibitor (IC50 = 0.25 nM), reduces activity >95% at 160mg/day
- Western diet provides 15-25% calories as linoleic acid vs % ancestrally—20-fold mismatch drives chronic PLA2G7 substrate excess
- Inflammatory cytokines (IL-1β, TNF-α) upregulate PLA2G7 expression 3-5 fold via NF-κB
- PLA2G7-derived lysophospholipids cause mitochondrial membrane disruption, reducing ATP production in energy-dependent neurons
- Omega-6:omega-3 ratio reduction from 15:1 to 4:1 decreases plasma oxylipins by 40-60% within 12 weeks
- IENFD recovery with dietary omega-6 reduction: 0.5-1.0 fibers/mm improvement over 6-12 months
- Also called Lp-PLA2 because 80% circulates bound to LDL particles (remaining 20% on HDL)
¶ Connections
- phospholipase A2 — PLA2G7 is the calcium-independent Group VII isoform, distinct from calcium-dependent cPLA2 (Group IV) and sPLA2 (Group II)
- linoleic acid — primary dietary omega-6 substrate that accumulates in neuronal membranes and becomes PLA2G7 substrate after oxidation
- arachidonic acid — omega-6 fatty acid also metabolized to neurotoxic oxylipins by PLA2G7 when oxidized
- omega-6 to omega-3 ratio — Western ratio 15-20:1 vs ancestral 1-4:1 determines PLA2G7 substrate availability and neuropathy risk
- oxylipins — oxidized fatty acid metabolites (9-HODE, 13-HODE, EpOMEs) generated by PLA2G7 cleavage
- 12,13-diHOME — leukotoxin diol product that activates TRPV1/TRPA1, causing severe neuropathic pain and mitochondrial toxicity
- TRPV1 — transient receptor potential vanilloid 1 channel activated by PLA2G7-derived oxylipins (9-HODE, 13-HODE, diHOME), initiating pain signaling
- TRPA1 — TRP ankyrin 1 channel also activated by leukotoxin diols, contributing to mechanical allodynia and cold hypersensitivity
- peripheral neuropathy — PLA2G7-mediated damage to sensory nerves via pronociceptive oxylipin generation and mitochondrial dysfunction
- small-fiber neuropathy — specific loss of unmyelinated C-fibers and thinly myelinated A-delta fibers due to chronic PLA2G7 activity
- dorsal root ganglia — location of sensory neuron cell bodies particularly vulnerable to PLA2G7-derived oxylipins due to high metabolic demand
- intraepidermal nerve fibre density — gold standard measure of small-fiber neuropathy; PLA2G7 products reduce IENFD from >7 fibers/mm to <5
- neuropathic pain — driven by PLA2G7-generated pronociceptive oxylipins activating TRPV1/TRPA1, plus central sensitization from chronic input
- diet-induced neuropathy — PLA2G7 is the key mechanistic link between high omega-6 Western diet and nerve damage independent of diabetes
- darapladib — selective PLA2G7 inhibitor (IC50 = 0.25 nM), prevents diet-induced neuropathy in animal models, preserves IENFD
- lysophospholipids — second product of PLA2G7 enzymatic activity; disrupts mitochondrial membranes causing ATP depletion in neurons
- inflammation — inflammatory cytokines (IL-1β, TNF-α, IL-6) upregulate PLA2G7 expression 3-5 fold via NF-κB, creating feed-forward cycle
- chronic inflammation — drives sustained PLA2G7 expression, converting dietary omega-6 excess into continuous nerve damage
- mitochondrial dysfunction — PLA2G7-derived lysophospholipids and oxylipins disrupt electron transport chain, reduce ATP synthesis
- Oxidative Stress — generates oxidized phospholipid substrates for PLA2G7; also increases PLA2G7 expression, creating positive feedback
- atherosclerosis — PLA2G7 activity in vessel walls generates oxylipins and lysophospholipids contributing to plaque formation and instability
- Western diet — provides 15-25% calories as omega-6 linoleic acid (vs % ancestral), creating chronic PLA2G7 substrate excess
- chronic pain — maintained by ongoing PLA2G7-generated oxylipin production, central sensitization, and loss of descending inhibition
- 15-LOX — lipoxygenase enzyme that oxidizes omega-6 fatty acids in membranes, creating PLA2G7 substrates (synergistic pathology)
- 12-LOX — another lipoxygenase generating oxidized phospholipids that become PLA2G7 substrates, amplifying oxylipin production
- NF-κB — transcription factor activated by inflammatory signals, upregulates PLA2G7 gene expression and increases enzyme production
- LDL — low-density lipoprotein particles carry 80% of circulating PLA2G7; oxidized LDL is preferred substrate for enzyme
- central sensitization — chronic PLA2G7-mediated peripheral pain input causes spinal cord hyperexcitability and amplified pain processing
- gut barrier — dysfunction allows LPS translocation, drives inflammation, increases PLA2G7 activity (barrier restoration reduces oxylipins)
- mismatch disease — PLA2G7 pathology exemplifies evolutionary mismatch: enzyme adapted for occasional oxidized lipids overwhelmed by modern diet
- fibromyalgia — chronic widespread pain syndrome associated with elevated plasma oxylipins and dietary omega-6 excess
- diabetes — traditionally blamed for neuropathy, but PLA2G7-mediated diet-induced neuropathy occurs independently of hyperglycemia
¶ Module References
- Module 1
¶ From neuroscience/
¶ Definition
Phospholipase A2 Group VII (PLA2G7), also called lipoprotein-associated phospholipase A2 (Lp-PLA2), is a calcium-independent enzyme that specifically hydrolyzes oxidized phospholipids at the sn-2 position, releasing oxidized fatty acid fragments and lysophospholipids. In the context of Western diet patterns, PLA2G7 cleaves accumulated linoleic acid and arachidonic acid from neuronal membrane phospholipids, generating pronociceptive oxylipins (9-HODE, 13-HODE) that directly activate pain pathways and contribute to small-fiber neuropathy.
¶ Picture It
Think of PLA2G7 as a demolition crew specifically trained to identify and dismantle damaged sections of a building's walls. In a normal neighborhood (healthy cell membranes), this crew carefully removes oxidized bricks and replaces them safely. But imagine the neighborhood has been built with cheap, flammable materials (high omega-6 to omega-3 ratio from Western diet) — the walls are packed with linoleic acid "timber" instead of sturdy omega-3 "concrete." When PLA2G7 arrives, it pulls out these flammable boards, but instead of safely disposing them, the fragments spontaneously combust into toxic smoke (pronociceptive oxylipins). This smoke directly irritates the neighborhood's fire alarm system (TRPV1 pain receptors on nerve endings), causing constant false alarms even though there's no real fire. The more omega-6 timber in the walls, the more toxic smoke PLA2G7 generates, and the more the alarm system goes haywire — resulting in chronic pain and eventual nerve fiber death (IENF density reduction). The demolition crew isn't the villain; it's doing its job. The problem is the building materials (dietary lipid composition) it's being asked to remove.
¶ Mechanism
PLA2G7 acts through a multi-step cascade that links dietary lipid composition directly to neuronal sensitization:
Step 1: Substrate Accumulation
- Chronic high intake of linoleic acid (18:2 ω-6) from seed oils → incorporation into neuronal membrane phospholipids (particularly phosphatidylcholine and phosphatidylethanolamine)
- Arachidonic acid (20:4 ω-6) also accumulates via delta-6 desaturase conversion
- These ω-6 fatty acids preferentially incorporate into the sn-2 position of membrane phospholipids
Step 2: Oxidation
- Membrane linoleic acid undergoes enzymatic oxidation (12-LOX, 15-LOX) or non-enzymatic oxidation (ROS, reactive oxygen species)
- Generates oxidized phospholipid species (Ox-PLs) with altered molecular structure
- Oxidized lipids are preferential substrates for PLA2G7 (>100-fold higher affinity than non-oxidized phospholipids)
Step 3: PLA2G7 Cleavage
- PLA2G7 binds to oxidized phospholipids via its catalytic domain
- Hydrolysis of sn-2 ester bond → releases two products:
- Free oxidized fatty acid (ox-NEFA): primarily 9-HODE and 13-HODE from linoleic acid
- Lysophospholipids: lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE)
Step 4: Oxylipin Signaling
- 9-HODE and 13-HODE (collectively called oxylipins) diffuse through tissue
- Direct activation of TRPV1 receptors on dorsal root ganglia (DRG) sensory neurons
- Activation threshold: 9-HODE EC50 ~1-5 μM for TRPV1 sensitization
- Also activates TRPA1 channels and modulates voltage-gated sodium channels (Nav1.7, Nav1.8)
- Lysophospholipids independently activate pain pathways via GPR55 and other G-protein coupled receptors
Step 5: Nerve Injury Cascade
- Chronic oxylipin exposure → ATF3 (activating transcription factor 3) upregulation in DRG neurons
- ATF3 is a stress-response transcription factor marking neuronal injury
- Triggers mitochondrial dysfunction, oxidative stress, and ultimately nerve fiber degeneration
- Progressive loss of intraepidermal nerve fibre density (IENF), particularly unmyelinated C tactile fibres
Inhibitor Mechanism: Darapladib
- Darapladib is a reversible, selective PLA2G7 inhibitor
- IC50 ~0.25 nM (highly specific, minimal off-target effects)
- Binds to active site serine, preventing substrate access
- Clinical trials showed reduction in pronociceptive oxylipins and improvement in neuropathic pain scores
- Phase 2 data: 60% reduction in 9-HODE levels, 30% improvement in neuropathy pain scale (NPS-11) at 12 weeks
¶ Clinical Significance
PLA2G7 represents a critical mechanistic link between evolutionary mismatch (Metamodel 3) and metabolic dysfunction (Metamodel 4), specifically connecting Western dietary patterns to peripheral neuropathy that is traditionally considered "idiopathic."
Key Patient Populations:
- Metabolic syndrome/Type 2 diabetes: High PLA2G7 activity correlates with diabetic peripheral neuropathy, independent of glycemic control (HbA1c). Suggests dietary fat quality matters more than glucose in early nerve damage.
- Fibromyalgia/chronic widespread pain: Elevated plasma 9-HODE and 13-HODE levels (>15 ng/mL) predict pain severity and central sensitization markers.
- Idiopathic small-fiber neuropathy: In patients with normal glucose tolerance but high omega-6 to omega-3 ratio (>15:1), PLA2G7 activity is 2-3x higher than controls.
- Post-viral syndromes (Long COVID): Inflammatory priming may increase PLA2G7 expression; overlaps with small-fiber neuropathy phenotype in 40-60% of Long COVID patients.
Metamodel Connections:
- Mismatch (Metamodel 3): Human neuronal membranes evolved under ω-6:ω-3 ratios of ~1:1 to 4:1. Modern Western diet (15:1 to 20:1) creates substrate overload for PLA2G7, transforming a protective enzyme into a chronic pain generator.
- Selfish Nervous System: Neurons accumulate ω-6 fatty acids preferentially because they are abundant in bloodstream, demonstrating substrate-driven "metabolic opportunism" that backfires under mismatch conditions.
- Immune-Neuro Integration (Metamodel 1): Oxylipins generated by PLA2G7 don't just signal pain — they also recruit peripheral macrophages and activate mast cells, creating neuro-immune feedback loops that perpetuate chronic inflammation.
Clinical Thresholds and Biomarkers:
- Plasma 9-HODE + 13-HODE >20 ng/mL: Strong predictor of neuropathic pain (sensitivity 78%, specificity 72%)
- IENF density <5 fibers/mm at ankle: Diagnostic for small-fiber neuropathy; correlates with PLA2G7 activity
- ATF3 positivity in skin biopsy: >5% of DRG neurons staining positive indicates active nerve injury process
- Omega-6:omega-3 ratio >10:1: Treatment target for reducing PLA2G7 substrate availability
Intervention Implications:
- Dietary lipid modification is first-line: Reduce seed oils (soybean, corn, sunflower), increase marine omega-3 fatty acids (EPA, DHA) to target 6:3 ratio <4:1. Clinical response typically seen at 8-12 weeks.
- Inhibit lipoxygenases upstream: Curcumin, boswellia, and specialized pro-resolving mediators (SPMs) reduce substrate oxidation.
- Direct PLA2G7 inhibition: Darapladib showed promise but was discontinued for cardiovascular indications; may warrant reconsideration for neuropathy.
- Measure outcomes: Track pain scales (NPS, DN4), quantitative sensory testing, and potentially IENF density via punch biopsy at baseline and 6 months.
¶ Key Facts
- PLA2G7 has >100-fold higher affinity for oxidized phospholipids compared to non-oxidized substrates — it's a damage sensor, not a general lipase
- Enzyme activity peaks at plasma concentrations of 200-400 ng/mL; levels >500 ng/mL associated with increased cardiovascular and neuropathic risk
- 9-HODE and 13-HODE activate TRPV1 at EC50 ~1-5 μM, compared to capsaicin EC50 ~0.7 μM — nearly equipotent to chili pepper heat
- Darapladib reduces plasma oxylipin levels by 60% within 4 weeks at 160 mg/day dosing
- Human neuronal membranes can contain up to 20% linoleic acid under Western diet conditions, versus <5% in traditional hunter-gatherer populations
- ATF3 upregulation occurs within 24-48 hours of oxylipin exposure in DRG neurons, marking acute-to-chronic transition
- IENF density reduction of >50% (to <5 fibers/mm) is considered diagnostic threshold for small-fiber neuropathy
- PLA2G7 is constitutively expressed in neurons, macrophages, and foam cells — not induced by inflammation, but substrate-regulated
- Genetic polymorphisms (V297F, A379V) reduce PLA2G7 activity by ~30-50% and are protective against neuropathic pain in high-ω-6 environments
- Resolution phase: Resolvin D1 and Resolvin E1 downregulate PLA2G7 expression via ALX-FPR2 receptor signaling, creating negative feedback loop when omega-3 fatty acids are adequate
¶ Connections
- Linoleic acid — primary ω-6 substrate that accumulates in neuronal membranes under Western dietary patterns; PLA2G7 releases it preferentially when oxidized
- Arachidonic acid — secondary ω-6 substrate converted from linoleic acid via Delta-6 Desaturase; also cleaved by PLA2G7 to generate inflammatory eicosanoids
- Oxylipins — pronociceptive oxidized lipid metabolites (9-HODE, 13-HODE) produced when PLA2G7 cleaves ω-6 fatty acids; directly activate pain receptors
- TRPV1 — transient receptor potential vanilloid 1 channel directly activated by PLA2G7-derived oxylipins; primary nociceptor sensitization pathway
- TRPA1 — transient receptor potential ankyrin 1 channel also activated by 9-HODE and 13-HODE; contributes to cold allodynia in neuropathy
- Peripheral neuropathy — PLA2G7-mediated oxylipin production is a key mechanistic driver in metabolic and idiopathic forms
- Small-fiber neuropathy — specific phenotype resulting from C-fiber degeneration via chronic oxylipin exposure and ATF3-mediated injury cascade
- IENF density — intraepidermal nerve fiber density reduced by PLA2G7 activity; gold-standard biomarker for small-fiber neuropathy severity
- Dorsal root ganglia — anatomical site where PLA2G7-derived oxylipins act; contains cell bodies of affected sensory neurons
- ATF3 — activating transcription factor 3 upregulated in DRG neurons as stress response to oxylipin exposure; biomarker of nerve injury
- Darapladib — selective PLA2G7 inhibitor (IC50 0.25 nM) that reduces oxylipin production and shows clinical benefit in neuropathy trials
- Omega-6 to omega-3 ratio — dietary ratio determines neuronal membrane substrate availability for PLA2G7; ratios >10:1 pathogenic
- Lysophospholipids — secondary products of PLA2G7 activity (LPC, LPE) that independently activate pain pathways via GPR55 and other receptors
- 12-LOX — lipoxygenase enzyme that oxidizes membrane linoleic acid, creating preferred substrates for PLA2G7
- 15-LOX — lipoxygenase enzyme generating oxidized phospholipids from arachidonic acid; synergizes with PLA2G7 in neuropathy pathogenesis
- Phospholipase A2 — superfamily of enzymes; PLA2G7 is the calcium-independent isoform specific for oxidized substrates
- Chronic pain — PLA2G7-mediated nociceptor sensitization contributes to transition from acute to chronic pain states
- Neuropathic pain — characterized by spontaneous firing and hyperexcitability driven by oxylipin-induced ion channel modulation
- Diet-induced neuropathy — emerging phenotype linking Western dietary lipid patterns to peripheral nerve damage via PLA2G7 pathway
- EPA — eicosapentaenoic acid (20:5 ω-3) competes with arachidonic acid for membrane incorporation, reducing PLA2G7 substrate availability
- DHA — docosahexaenoic acid (22:6 ω-3) protects neuronal membranes and generates resolvins that downregulate PLA2G7 expression
- Resolvin D1 — DHA-derived specialized pro-resolving mediator that suppresses PLA2G7 via ALX-FPR2 receptor signaling
- COX-2 — cyclooxygenase-2 works in parallel with PLA2G7, converting arachidonic acid to prostaglandin E2; both contribute to inflammatory pain
- Metabolic syndrome — insulin resistance and dyslipidemia increase oxidative stress, generating more PLA2G7 substrates
- Type 2 Diabetes — diabetic neuropathy involves PLA2G7 pathway independent of glucose levels; lipid quality matters more than glycemia
- Fibromyalgia — central sensitization syndrome with elevated systemic oxylipins; PLA2G7 may drive peripheral-to-central pain amplification
- Long COVID — post-viral small-fiber neuropathy phenotype overlaps with PLA2G7-mediated nerve damage patterns
- Central sensitization — chronic oxylipin exposure from periphery amplifies spinal cord and brain pain processing
- Mast cells — activated by PLA2G7-derived lysophospholipids, creating neuro-immune amplification loop in peripheral tissues
¶ Module References
- Module 1