Perineural Injection Therapy: The Technique That Does Not Need Inflammation

Written by Robert Stall, MD

Updated September 2026 ·9 min read

Perineural injection therapy is the outlier in regenerative medicine, and the reason is mechanistic: it is the only technique in the category that does not work by provoking inflammation.

Robert Stall, MD, who teaches it for Empire, describes it as acting “through the nervous system to re-establish more normal homeostasis in tissue repair and regeneration” — and notes that unlike other regenerative modalities “it does not require the induction of an inflammatory response and it is painless or relatively painless.”

It is sometimes called neural prolotherapy, though that name obscures the distinction that matters.

What is injected, and where

Small volumes of 5% dextrose in sterile water, buffered to physiologic pH. No anaesthetic, no steroid, nothing exotic.

The solution goes into subcutaneous tissue around cutaneous nerves that have become chronically injured or inflamed — superficially, not into a joint or deep structure. That placement is why Stall describes PIT as “the safest modality within regenerative medicine, with the fewest contraindications and a wide range of indications,” and as a reasonable point of entry “for new injectors and people who do not possess specialised training or specialised equipment.”

Injection sites are found by palpation rather than imaging — the clinician locates painful, swollen peripheral nerves on examination.

The mechanism, step by step

The account Stall teaches is a specific physiological cascade rather than a general appeal to healing.

Ischaemia from compression or other injury sets off a chain: microvascular ischaemia leads to local metabolic block, which depletes neuronal energy resources, producing depolarisation and discharge. That activates the TRPV1 ion channel, which releases substance P and CGRP — calcitonin gene-related peptide — both of which induce neurogenic inflammation.

C fibres are particularly susceptible to this depolarisation compared with larger-diameter axons. TRPV1 itself mediates neuropathic pain and can be stimulated by capsaicin, by mechanical pressure, by ischaemia and by hyperosmolarity.

The intervention targets the energy-depletion step. Buffered 5% dextrose corrects what Stall describes as the underlying glycopenia of the nerve — restoring the energy substrate whose absence started the cascade. As he puts it, the pain and swelling from increased substance P release “can be treated with buffered D5W.”

Which explains the unusual property of the technique: analgesia without anaesthesia. The patient has less pain and improved movement, but no numbness and no loss of protective sensation, because nothing has been blocked.

Why these small nerves matter more than their size suggests

The fibres PIT targets are not merely small pain nerves.

Stall describes them as part of the neuroendocrine system, forming connections between the superficial cutaneous systems and the deep myofascial and skeletal systems. They are also the principal fibres involved in interoception — the capacity to sense what is happening inside your own body, consciously and unconsciously, through the sympathetic and parasympathetic nervous systems.

And they are everywhere: present in virtually every tissue from hyaline cartilage to tendon and ligament, muscle, lung and internal organs.

That distribution is why a superficial subcutaneous injection can influence symptoms arising from structures well beneath it, which otherwise looks implausible.

What it is used for

Neurogenic inflammation is, in Stall's framing, “both a cause of and a consequence of chronic pain syndromes and acute injury” — which gives the technique a broad range of application wherever superficial nerves are palpably tender and swollen.

His teaching includes specific protocols. For the hip, a simple protocol targets all three major nerves contributing articular branches to the femoroacetabular joint — femoral, obturator and sciatic. For a symptomatic Baker's cyst, injection is unlikely to resolve the cyst itself, but since the cyst is usually painless until it becomes large enough to act as a space-occupying lesion, reducing its size may resolve the symptoms.

How often it is repeated

PIT follows a different schedule from PRP, and the difference follows from the mechanism.

Because nothing is waiting on a collagen remodelling cycle, injections are repeated weekly as needed until the pain diminishes or resolves, or until the patient stops responding to treatment.

That last clause is the useful one. A defined stopping rule — continue while improving, stop when improvement stops — is more honest than a fixed package, and it is what should be agreed before starting.

Benefit, once established, can persist for weeks or months after injection.

How it compares with the rest of the category

What to be careful about

Two things deserve saying plainly.

The published evidence base for PIT is thinner than for PRP in tendon indications. The mechanism is well described and the safety profile is favourable, but that is not the same as a body of randomised trials, and anyone presenting it as settled is overstating.

Second, its accessibility cuts both ways. A technique that needs no imaging and no specialised equipment is easy to adopt — and equally easy to apply without the examination skill it depends on. The whole method rests on palpating the right nerves. Without that, the injection is in the wrong place, and no amount of dextrose corrects it.