Proposals (P1–P6)

Six directional proposals follow from the map: intervene at the peripheral nociceptor gate (P1), push it to raise the firing threshold (P2), rank effectors by selectivity and map place pursuing the Na_V triad (P3), favour a state-dependent shape (P4), pursue a structurally non-reward opioid alternative (P5), and pursue pain-selective local anaesthesia (P6). Each is a hypothesis, not a result.

Six proposals (P1–P6) state directional hypotheses that follow from the map — where to intervene, which way to push, which axis to pursue, which mechanism shape to favour, why it is a structural opioid alternative, and how to make a differential block. Each is a hypothesis to test; whether any molecule reaches the goal is an open empirical question.

Six directional proposals follow from the map. Each is a hypothesis to be tested, not a result; each names its falsifier on the falsification page.

Proposals (P1–P6)

Six directional proposals follow from the map. Each is a hypothesis to be tested, not a result.

  1. P1. Intervene at the nociceptor-restricted firing gate in the peripheral sensory neuron rather than at a central site.
  2. P2. Push that gate in the direction that raises the effective firing threshold and restores the OFF basin, while preserving protective high-threshold nociception.
  3. P3. Rank candidate effectors by nociceptor-selectivity together with their position in the threshold map; pursue the sodium-channel triad as the primary axis — NaV1.8 most peripherally selective, then NaV1.9, then NaV1.7 — with TRPV1 and TRPA1 as the transduction arm.
  4. P4. Favour a state-dependent mechanism that stabilises the closed or inactivated channel state — the shape that lifts the firing threshold while leaving ordinary low-frequency conduction largely intact.
  5. P5. Because the targeted gate is peripheral and nociceptor-restricted, this direction is pursued as an opioid alternative that structurally does not engage central reward circuitry; whether any particular molecule reaches that goal is an open empirical question, decided only by laboratory and clinical work.
  6. P6. Pursue pain-selective local anaesthesia by pairing a nociceptor-selective entry port (TRPV1 or TRPA1) with a charged firing-threshold raiser that enters only through that open port, so the block is differential — nociceptive fibres silenced, motor and light-touch fibres largely spared (see §5); the differential-block magnitude is an open empirical question, not a claim made here.