2026 — Ketamine review for acute and chronic pain (NMDA-glutamatergic mechanism anchor)
One-paragraph summary
Narrative review of ketamine as a non-opioid analgesic across acute, perioperative, and chronic pain settings. Mechanism: noncompetitive NMDA receptor antagonist; attenuates central sensitization; modulates opioid tolerance; enhances descending inhibitory control. At subanaesthetic doses (0.1-0.5 mg/kg), consistent reduction in pain scores and postoperative opioid consumption with maintained hemodynamic/respiratory stability. In acute/perioperative care, analgesic efficacy comparable to opioids. In chronic pain — particularly CRPS — variable but documented efficacy. For the project, this paper directly addresses the v0.3-era GRIN1-NMDA cure-path-arm gap (Dogan 2026's serum GRIN1 NMDA biomarker finding in FM has had no corresponding intervention class until now). Ketamine becomes a candidate cure-path-arm-consideration via the new B27 bridge (NMDA antagonist + serotonergic psychedelic ↔ chronic pain) added today from the over-regulation audit.
Claims as triples
ketamine — modulates → central_sensitization[evidence: NMDA antagonism review; confidence: established]ketamine — modulates → descending_inhibition_failure[evidence: enhanced descending inhibitory control mechanism review; confidence: emerging]ketamine — bridges → fm_central_only[evidence: chronic-pain efficacy + GRIN1 mechanism overlap with Dogan 2026; confidence: bridging]
Triangulation notes
- Closes the GRIN1-NMDA cure-path-arm gap that has been open since Dogan 2026's serum GRIN1 biomarker finding (FM diagnostic biomarker, AUC 0.78-0.84). Ketamine becomes the candidate intervention class for the NMDA-modulation arm.
- Compatible with B27 (NMDA antagonist + serotonergic psychedelic ↔ chronic pain), the new bridge added 2026-05-10.
- Discovered via Probe 7 (ketamine/psychedelic-assisted therapy); scored ingestion-worthy; promoted in Recommendation 3.
Open questions raised
- Does ketamine reduce serum GRIN1 levels in FM patients?
- Does ketamine produce durable vs. transient analgesia in FM (sub-anaesthetic vs. infusion-based dosing)?
- Pre-specified retirement trigger for any future ketamine-in-FM arm (per cure-path-arm decision protocol): if a stratified RCT in GRIN1-positive FM patients with subanaesthetic ketamine infusion fails to reduce FIQ-R at 12 weeks, the arm should be RETIRED rather than further reframed.