PDLLA: both randomised trials we found measured pain, not efficacy

We verified two randomised PDLLA trials on PubMed. Here is what each measured.

First, a 2026 trial — pain by injection depth. Twenty-one participants received ten facial injections each (five intradermal, five subdermal), with a 32G needle, in a randomised double-blinded split-injection design. The endpoint was the visual analogue scale (VAS).

Second, a 2025 trial — pain by side of the face. Twenty Korean patients (13 women, 7 men, aged 22 to 67) received intradermal PDLLA in both cheeks over four sessions at three-week intervals, with VAS recorded immediately after each injection. The result: the left side consistently hurt more than the right (P < .05), and the analysis was also broken down by sex and age.

Neither trial measured efficacy.

How much wrinkles softened, how much texture improved, how either compared with a vehicle or saline — we found no randomised controlled trial answering those questions.

We consider that fact itself to be information.

The PLLA page on this site has a superiority trial with 331 participants. Two substances one letter apart, and the evidence behind them is that different in depth.

And look once more at the second trial's result — the left side hurts more. The same substance went into both cheeks of the same person, and one side hurt more. That means injection pain is not settled by the substance alone, and that the experience of a procedure is moved by several things at once.

The 2026 trial in detail. It is a randomised, double-blinded, split-injection design, and by this site's standards the design itself is solid.

• Twenty-one participants
• Ten injections each in the face — five intradermal, five subdermal
• 32G needle
• Randomised, double-blinded

Because each person experienced both depths, individual differences in pain threshold do not blur the result.

The result: intradermal VAS 6.18, subdermal 3.85. P < .001.

That is a 2.33-point gap on a ten-point scale. Not a small difference statistically, and not a small one to feel either.

The anatomy suggests why. Sensory nerve endings are far denser in the dermis. That shallower hurts more is not surprising.

What this is useful for. For someone considering a skin booster, this trial offers information about the experience, not about the effect. If you decide to have it done, it is worth knowing that injection depth moves the pain a lot, and that the depth is something you can discuss with your clinician.

That the endpoint is self-reported pain is written on the badge as it stands. Pain is by nature something only the person can know, so this endpoint is appropriate here — unlike the PRP page, where self-rating became the problem. There, people were rating visible improvement; here, they are rating how much it hurt.

Twenty-one is a small number, and there is no follow-up period to speak of — the assessment is immediate. So it sits at 'early evidence'.

The concluding sentence of that trial contains a clause to the effect of: 'with equivalent efficacy and minimal downtime, subdermal injection …'

Read one way, it is a natural sentence. If it hurts less and works the same, choosing the less painful route is sensible.

But this trial did not measure efficacy.

Whether intradermal and subdermal injection produce the same result for wrinkles or texture is something this trial did not check. It measured pain. 'Equivalent efficacy' is not something the trial concluded; it is something it assumed.

We point this out not to fault the authors. Papers routinely take as given the assumptions that circulate in clinical practice.

We write it because a reader must not read that sentence as 'the two depths have been shown to be equally effective'. What was shown is only that one of them hurts more.

This is the thing this site does again and again on the procedure pages: separating what a paper measured from what a paper said. It is the same work as reading the same two trials from both sides on the CaHA and PLLA pages.

And the gap this item points at is a practical one. At what depth should PDLLA go in? is a question that matters to the person receiving it — and pain has an answer while effect does not yet.