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

A clear pain reduction on the Visual Analogue Scale (VAS) was demonstrated for one out of four participants receiving combined probiotics and PEA treatment.

• The study used a multiple baseline design (MBD) over 11 weeks with four participants recruited from a naturopathic practice.
• The primary outcome was daily pain scores using a Visual Analogue Scale (VAS).
• Visual analysis of time series graphs and descriptive statistics were used to analyse the data.
• Only one participant showed a clear pain reduction, suggesting individual variability in response to treatment.

Improvements in patient-specified functional scales, wellbeing, and anxiety were suggested for all four participants during the active intervention phase.

• 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.
• Improvements in wellbeing and anxiety were observed across all participants, not just those showing pain reduction.
• These findings were based on visual analysis and descriptive statistics rather than inferential statistical testing.

The study employed a double-blind multiple baseline design with two randomised pathways, both beginning with a placebo phase followed by active treatment with probiotics and PEA.

• 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 study ran over 11 weeks with four participants recruited from a naturopathic practice.
• The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN#:12621000039886) on 18 January 2021.

PEA is an endogenously produced N-acylethanolamine with analgesic and mood-modulating effects that primarily acts via non-cannabinoid pathways, most notably through activation of peroxisome proliferator-activated receptor alpha (PPARα).

• PEA is described as 'endocannabinoid-like' due to its structural similarity to endocannabinoids, but has non-direct influence on the endocannabinoid system.
• PEA has demonstrated both analgesic (pain-relieving) and mood-modulating effects in preclinical studies and preliminary clinical studies.
• At the time of this study, no clinical studies had investigated the combined use of PEA and probiotics for the treatment of OA pain.
• Both PEA and probiotics were selected as therapeutic candidates due to their anti-inflammatory properties.

This was the first clinical study to investigate the combined use of PEA and probiotics for the treatment of osteoarthritis pain.

• The authors note that 'to date, no clinical studies have investigated the combined use of PEA and probiotics for the treatment of OA pain.'
• The study is described as preliminary and hypothesis-generating.
• Osteoarthritis is identified as a leading cause of chronic pain, with many individuals self-managing their symptoms.
• The authors conclude that findings warrant evaluation in larger, controlled studies.