Narrower indications

• Joint pain — 2 graded rows from 3 compounds checked
• Neuropathic pain — 2 graded rows from 2 compounds checked

Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. ARA-290

   human RCT Direct outcome In registered trials

   Who was studied

   patients with sarcoidosis and symptoms of small-fibre neuropathy, n=22 (12 on ARA 290, 10 on placebo), 2 mg intravenously three times weekly for 4 weeks

   A randomised, double-blind placebo-controlled pilot trial measured the Small Fibre Neuropathy Screening List, the SF-36 pain dimension and the Brief Pain Inventory. SFNSL and the SF-36 pain dimension improved more on ARA 290 than on placebo, but Brief Pain Inventory scores fell equivalently in both arms. The population is sarcoidosis-associated small-fibre neuropathy only; no trial of ARA 290 in pain of other causes is on file, and it has no regulatory approval anywhere.

   Source PubMed Central 2 primary sources read for this row

2. Collagen Peptides

   human RCT Direct outcome Not approved for this condition

   Who was studied

   adults aged 40-75 with mild to moderate knee osteoarthritis (Kellgren-Lawrence grade I-III), pooled n=507 across 4 randomised placebo-controlled trials; oral doses of 2-10 g daily for 90-180 days

   A meta-analysis of four randomised placebo-controlled trials pooled 100 mm visual analogue scale pain scores in knee osteoarthritis and reported a standardised mean difference of -0.58 (p = 0.004) favouring oral collagen peptides, graded moderate quality. The population is knee osteoarthritis specifically; no trial in neuropathic, post-operative or generalised chronic pain is on file, and collagen peptides are a food ingredient with no regulatory approval for pain.

   Source PubMed Central 1 primary source read for this row

3. PEA

   human RCT Direct outcome Not approved for this condition

   Who was studied

   adults with chronic pain of mixed cause, pooled n=774 (383 on PEA, 391 controls) across 11 double-blind randomised trials; conditions included spinal cord injury and diabetic neuropathic pain, knee osteoarthritis, temporomandibular joint arthritis, carpal tunnel syndrome, endometriosis-related pelvic pain, dysmenorrhoea, vestibulodynia, irritable bowel syndrome and burning mouth syndrome; durations 10 days to 12 months, most 8-12 weeks

   A 2023 systematic review and meta-analysis of 11 double-blind randomised trials pooled pain intensity measured on visual analogue, numeric rating or Likert scales and reported a standardised mean difference of 1.68 (95% CI 1.05 to 2.31) favouring oral palmitoylethanolamide over comparator. The pooled population is heterogeneous - neuropathic, musculoskeletal and gynaecological pain were combined - so the estimate is not specific to any one pain type, and PEA is sold as a food supplement rather than approved by any regulator for pain.

   Source PubMed Central 2 primary sources read for this row

4. Cartilage Peptides

   human case series Direct outcome Not approved for this condition

   Who was studied

   adults with moderate knee joint discomfort and loss of function, n=33, 1000 mg fish cartilage hydrolysate orally once daily for 3 months; no control group

   An exploratory, non-comparative, multi-centre study measured the Knee injury and Osteoarthritis Outcome Score and reported improvement in the knee pain and function subscales. There was no placebo arm and no randomisation, so improvement cannot be separated from natural course or expectation; the authors state the result needs confirmation in a randomised controlled trial. The population is knee joint pain, not pain generally.

   Source PubMed Central 1 primary source read for this row

Checked, and nothing recorded

10 compounds were checked against pain and produced no gradeable row.

• Bradykinin — checked, no row on file
• Cartalax — checked, no row on file
• Dynorphin A — checked, no row on file
• Galanin — checked, no row on file
• Leu-Enkephalin — checked, no row on file
• Met-Enkephalin — checked, no row on file
• Neurotensin — checked, no row on file
• Nociceptin — checked, no row on file
• Substance P — checked, no row on file
• β-Endorphin — checked, no row on file

A compound is here because someone looked and the sources did not support a row — not because nobody looked. Under the rubric, uncertainty resolves to no row, and a row resting on a vendor page or a clinic blog is worse than no row at all.