Analgesic target logic for the primary somatosensory nociceptor (inherited and re-derived on this volume own R19 engine): a DNA-grounded 27-target firing-threshold map sorted into three drug-class levers

This section brings home a sibling whitepaper — analgesic_threshold_logic v2.0 (DOI 10.5281/zenodo.20733420), a DNA-grounded map of 27 non-opioid analgesic targets — to its native organ, the primary somatosensory nociceptor (this volume master PRDM12, Na_V1.7 = SCN9A). Each pain gene measured promoter gamma sits on the R19 firing-threshold scale |h_sp| = spinodal(gamma), which is identically the firing threshold this volume sec.2/sec.19 already run, so re-deriving all 27 on this engine reproduces the inherited thresholds bit-for-bit (drift 0). The targets sort into three drug-class levers — reduce the inward current, open K_V7, remove the NGF/CGRP drive — each raising the firing threshold; efficacy, dose, and the felt pain stay [O]/mind.

analgesic_threshold_logic v2.0 (concept DOI 10.5281/zenodo.20733420, CC BY 4.0) was itself built ON this volume neuro engine: its reproduction engine is byte-identical to repro/neuro/_engine/vp_neuro_engine.py (asserted in-module, sha256 c933ee8dd948…). So the nociceptor firing threshold the analgesic map raises IS the |h_sp| = 2(g/3)^1.5 = spinodal(gamma) every cell in this volume runs. The engine reads each pain gene human promoter and returns gamma = −mean(NN stacking ΔG, SantaLucia 1998), places it on |h_sp|, and re-deriving all 27 target reads on this engine reproduces the inherited firing thresholds bit-for-bit (every displayed |h_sp| and barrier exact at the frozen precision, order identical, drift 0). The 27 targets sort into three intervention levers, all raising the same firing threshold from different directions: L1 reduce the inward (excitatory) current (12 channels + 1 adjacent), L2 increase the outward K+ current (3 K_V7), L3 remove the NGF/CGRP sensitising drive (6 ligand/receptor), with the master TF PRDM12 and 4 opioid/cannabinoid comparators read for contrast. The firewall is inherited verbatim: gamma reads promoter switch-threshold STRUCTURE only — never a channel voltage, a drug potency, a dose, an in-vivo selectivity, or a clinical effect; every such magnitude is [O]; the felt/affective pain is the Felt Cognition volume. No molecule is designed and nothing prescribes. The drift-0 re-derivation and the three-lever frame are [V]/[F]; every clinical magnitude is [O] with stated obstacles.

Every pain reading in this volume ends at the same question: which intervention raises the nociceptor firing threshold, and toward which drug class does the mechanism point. This section answers it by inheriting a sibling whitepaper, analgesic_threshold_logic v2.0 (DOI 10.5281/zenodo.20733420, CC BY 4.0). It is not a paste: that sibling was built on this very engine, so the inheritance is the same substrate read a second way.

The engine reads each pain gene human promoter and returns γ = −mean(NN stacking ΔG, SantaLucia 1998), then places γ on the R19 double-well firing-threshold scale |h_sp| = 2(g/3)^1.5 = (2/3√3)γ^1.5. That scale is this volume own spinodal(γ): re-deriving all 27 reads on it reproduces the inherited firing thresholds bit-for-bit (every displayed |h_sp| and barrier exact at the frozen precision, order identical — drift zero). The analgesic firing-threshold axis is the nociceptor spinodal of sec.2/sec.19; that identity is why the inheritance is principled.

The 27 targets sort into three intervention levers, all raising the same firing threshold from different directions: L1 reduce the inward (excitatory) current (block depolarising Na_V / Ca_V / ASIC / P2X / TRP channels), L2 increase the outward K⁺ current (open K_V7), L3 remove the up-stream sensitising drive (block NGF / CGRP). Ordered by the stiffest firing gate first:

Engine identity and drift. This volume engine is byte-identical to the engine the frozen sibling map was built on (sha256 c933ee8dd948210c…, asserted in-module). Re-deriving all 27 target reads on it reproduces the frozen |h_sp| and barrier exactly at the frozen precision, with identical spinodal order — the drift-zero inheritance that makes this volume the canonical home of the somatosensory reading (the digestive volume visceral-pain section points here).

Treatment (model reading). INHERITED analgesic target logic, read on this volume nociceptor. The firing threshold |h_sp| is raised — equivalently the afferent gain is lowered — by ANY of three levers: L1 reduce the inward current (the αδ-1 gabapentinoid class; the Na_V1.8 / P2X3 nociceptor-selective classes), L2 open the K_V7 brake (retigabine/flupirtine template), L3 remove the NGF/CGRP drive (anti-NGF / anti-CGRP). Class placement is [F] structural; efficacy, dose, and selectivity-in-vivo are [O]; the felt/affective pain is the Felt Cognition volume. No molecule is designed; nothing prescribes.

The firewall is non-negotiable and inherited verbatim: γ reads promoter switch-threshold STRUCTURE only — it is never a channel activation voltage, a drug potency, a dose, an in-vivo selectivity, or a clinical effect; every such magnitude and absolute efficacy are [O]; the lever strength is structural, not a dose; the L3 (NGF/CGRP) mechanism link is [O] cited biology; and the felt / affective pain is the Felt Cognition volume. This is a proposal-only target hypothesis.