Probiotics and palmitoylethanolamide (PEA) for osteoarthritic pain: individual effects in a multiple baseline design...

Osteoarthritis (OA) is a leading cause of chronic pain. As healthcare services struggle to meet demand to treat chronic pain, many individuals self-manage their symptoms. Probiotics and palmitoylethanolamide (PEA) may be promising therapeutic options because of their anti-inflammatory properties. PEA is an endogenously produced N-acylethanolamine, considered "endocannabinoid-like" due to its structural similarity to endocannabinoids. While it has non-direct influence on the endocannabinoid system, it primarily acts via non-cannabinoid pathways, most notably through activation of peroxisome proliferator-activated receptor alpha (PPARα). PEA has demonstrated both analgesic (pain-relieving) and mood-modulating effects in preclinical studies, and preliminary clinical studies. To date, no clinical studies have investigated the combined use of PEA and probiotics for the treatment of OA pain.

A multiple baseline design (MBD) study was used over 11 weeks to assess the individual effects in four participants recruited from a naturopathic practice. Participants were randomised into one of two pathways, both starting with a placebo phase, followed by an active intervention involving probiotics and PEA. This design allowed for the concealment and blinding of the introduction of active treatment in a double-blind manner. The primary outcome was daily pain scores using a Visual Analogue Scale (VAS). Secondary outcomes incorporated a patient-reported measure which was a patient specified functional scale. Other secondary outcomes assessed wellbeing, stress, and blood indicators of inflammation. Visual analysis of time series graphs and descriptive statistics were used to analyse the data.

The graph demonstrated a clear pain reduction for one participant. Analyses also suggested improvements in patient-specified functional scales, wellbeing, and anxiety for all participants.

This small multiple‑baseline study suggests that a probiotics‑plus‑PEA regimen may support function and wellbeing in some individuals with OA; these preliminary, hypothesis‑generating findings warrant evaluation in larger, controlled studies.

This trial was registered with the Australian New Zealand Clinical Trials Registry on the 18th of January 2021. The registration number is ACTRN#:12621000039886.