Falsification

Each proposal names the observation that would refute it: no threshold-driven reduction in nociceptive signalling, no Na_V-triad selectivity advantage, no state-dependent sparing of conduction, central reward engagement, or no differential block. The framework-level open question is whether the promoter γ read tracks expression-switch behaviour — stated, not assumed.

Each proposal is paired with the observation that would refute it, and the framework names its own falsifier — that the promoter γ read tracks expression-switch behaviour at these loci. Forced structural claims [F] are separated from the framework-level open question [O], which is stated rather than assumed.

What would break each claim

Each proposal names the observation that would refute it. A map that cannot be wrong is not science; these are the tests that can break it.

  1. P1/P2 — gate & direction. If raising the nociceptor firing threshold at these peripheral gates does not reduce nociceptive signalling in a controlled assay, the direction is wrong. [F]
  2. P3 — Na_V triad axis. If the sodium-channel triad does not behave as the most nociceptor-selective inward-current axis relative to the other levers, the ranking premise fails. [F]
  3. P4 — state-dependent shape. If a closed/inactivated-state stabiliser cannot lift the firing threshold while sparing ordinary low-frequency conduction, the favoured mechanism shape is falsified. [F]
  4. P5 — opioid-alternative claim. If a peripheral, nociceptor-restricted intervention nonetheless engages central reward circuitry, the opioid-alternative framing is falsified. [F]
  5. P6 — differential block. If opening a nociceptor-selective entry port (TRPV1/TRPA1) does not confine a charged Na_V blocker to nociceptive fibres — no differential block versus motor/touch fibres — the precision claim fails. [F]
  6. Framework. If the promoter γ read does not track expression-switch behaviour at these loci, the Layer-1 grounding of the whole map is falsified. This is the framework-level open question, stated not assumed. [O]