Neural prolotherapy (NPT) is a simple and very effective treatment for pain. It uses injection of sugar near cutaneous nerves to extinguish neurogenic pain and neurogenic inflammation. Science has found some of the reasons for the profound effects of sugar or sugar alcohols in these injections, but there is still more to be researched at this time. Nonetheless, NPT is so safe that it is worth a try in all pain conditions.
It has been found that NPT resolves 80% of all pain, as 80% of all pain is neuropathic or from neurogenic inflammation – meaning that the nerves become damaged and send a pain signal and cause inflammation.
The definition of neuropathic pain by Professor Douglas Zochodne states that it is: "a severe and debilitating pain that can render patients unable to walk, work, sleep or enjoy life. … Full and effective regeneration of the peripheral nervous system usually extinguishes this pain."1 John Lyftogt, MD, of Christchurch, New Zealand, has researched and developed the science of identifying and treating neuropathic pain and neurogenic inflammation with injections of 5% dextrose (D5W) or mannitol (M5W) near the damaged or inflamed nerves. This extinguishes the pain and inflammation immediately and is diagnostic for neuropathic pain and neurogenic inflammation.
Lyftogt says that he first tried dextrose on his own chronic pains from injury. He was so impressed with the relief that he told his wife, and she volunteered her painful areas and had relief as well. After many successful treatments, he brought it into his practice. One of the first patients was a long-distance runner with debilitating Achilles tendonitis. In this case, Lyftogt treated the lateral sural nerve and lower saphenous nerve where they cross over the Achilles tendon with D5W. The patient was immediately out of pain. Having been unable to train for some time and now feeling better, the patient, like any devoted athlete, promptly went out and ran a 10K. When Lyftogt discovered this, he was surprised and intrigued that the running did not cause a relapse of the tendonitis. He recognized that the treatment had therapeutic value beyond pain relief, and he has since laid out the science and treatment of neuropathic pain. His patients were predominantly amateur and professional athletes with painful injuries, and with the treatment of their cutaneous nerves, he found that they got pain relief and could continue to train, because the injury (the damaged nerve) was healed. Lyftogt has learned that neurogenic inflammation can advance and worsen over time, so the sooner the original injury is treated, the fewer treatments are needed for complete healing.
The science of NPT developed by Lyftogt lays out the function and dysfunction of nerves when they are damaged. Neurogenic pain is caused by damage to the C fibers of cutaneous nerves. C fibers are unmyelinated nerves, about 1 micron in size, of low conduction velocity. In other words, they send a slow signal compared with other nerves. They were discovered in the 1960s with the invention of the electron microscope which allowed them to be visualized. C fiber nerves are afferent and efferent, which helps explain the complexity of experience of neurogenic pain. There is a receptor on the nerves called TRPV1 (transient receptor potential cation channel, subfamily V [vanilloid], member 1), whose previous name was the capsaicin receptor. TRPV1 is regarded as the central nerve receptor in initiating and maintaining pain-related behaviour in animals and pain experience in humans).2 They are responsible for the burning sensation often described in pain syndromes).3 For a direct experience of the burning pain by a TRPV1 receptor and its treatment using the principles of NPT, eat a hot chili pepper and then take a sip of a sugary drink and hold it in your mouth. You will find that the burning sensation is extinguished because the sugar changes the signal from the TRPV1 receptors in the nerves of your mouth. This is proposed to be the effect that is happening with the injections of dextrose.
TRPV1 is the principle mediator of:
• tissue maintenance and renewal
• inflammation and neuropathic pain
• pain with disease and degeneration
The TRPV1 receptors are activated by:
• noxious stimuli
• high temperatures
• pressure (greater than 30 mm Hg)
These stimuli cause the nerve to convey a pain/inflammation message to the central nervous system. It only takes pressure of 30 mm Hg or greater to compress the nerve enough to cause the pain. What happens is that the cutaneous nerves passes through the fascia into the subcutaneous space from deeper tissue. As the nerve passes through openings, these can be restive or the nerve can be swollen so that it is restricted. This causes compression of the nerve, and the nerve compression and subsequent damage is called a chronic constriction injury (CCI).4 CCIs can be palpated and occur by restriction of the fascia, entrapment in facial ligatures, or entrapment in scar tissue creating a scar neuroma. Exercise causes nerves to swell and become entrapped in these restricted areas either by adhesion or natural ligatures. Commonly a swollen nerve is restricted by a fascial opening, the myelin sheath, and can be stripped with movement or stretching, causing an intussuception injury, which is much like stripping the plastic cover off a wire – very painful for the patient.
For example, a common CCI results in low back pain. There is an osteofibrous tunnel, located 7 to 8 cm laterally from the midline of the spine on the posterior ileum. The affected nerve is the superior cluneal nerve and is from the L1, L2, or L3 nerve root. When a person bends forward the nerve stretches and should normally easily slide through the tunnel, but if the nerve is swollen, it gets caught in the fascial opening and adhesion (CCI), causing stripping and bunching of the myelin sheath with nerve tissue. This is an intussusception injury of the nerve. Patients with this type of nerve injury reports that their backs went out on them. They go for an exam and are usually diagnosed with a disc injury at L4–5 or L5–S1, a fairly common condition in people over 40 years old that doesn’t usually cause pain. The patient is prescribed back rest, the nerve swelling recedes, the nerve remylinates, and the pain goes away. Or the patient goes for surgery and has some or no relief because the cause of the nerve injury is not addressed by the surgery.
As the intussuception injury is repeated, the bunched-up nerve and sheath build up on one or both sides of the tunnel and enlarge over time. Patients call these palpable lumps their "marbles" or "back mice"; also they have had them diagnosed as lipomas with nerve infiltration. NPT is the ideal treatment for this type of low-back pain. The injection of D5W to the osteofibrous tunnel entrances and along the nerve course immediately relieves pain and improves range of motion. The patient is amazed and frequently has a confused look on his face due to the sudden absence of pain with movements that used to always be excruciating. Lyftogt states that the diagnostic criterion for neurogenic pain is if the pain goes away with treatment, then it’s neurogenic in origin.
Neurogenic inflammatory signals and pain signals are sent by the release of calcitonin gene-related peptide (CGRP) and substance P (SP).
These are documented effects of CGRP from Susan Brain in 1985:
- vasodilator of precapillary arterioles
- enhances the vascular permeability and protein extravasation effect of SP
- upregulation of VEGF causing neovascularisation and neoneurogenesis. VEGF increases MMP1 leading to collagenolysis (degeneration of tendons)
- increased tissue calcium levels (calcifications)
- stimulation of osteoclasts (dystrophy bone, stress fractures)
The documented effects of SP include:
- vasodilator of postcapillary venules which cause increased vascular permeability in postcapillary venules, leading to protein extravasation (tissue edema)
- chemoattractive to immune cells
- SP in a positive feedback loop is an important regulator of the immune system. Activates immune cells to produce cytokines
- binds to mast cells, causing degranulation
- affects the amygdala, causing depression
- stimulates CRH release in the hypothalamus, upregulating the HPA stress response. Prolonged activation may lead to exhaustion (DHEA depletion)
- sensitizes peptidergic nociceptors, leading to neuropathic pain with allodynia and hyperalgesia
- impairs propriocepsis by delaying antagonist muscle reflex inhibition (neurogenic inflammation of MEP)
- causes increased intramuscular compartment pressure
It is interesting that the same TRPV1 receptors in the C fibers also send a healing signal through the release of somatostatin and galanin, which are anti-inflammatory and reverse the effects of the CGRP and SP. This mechanism has not been studied as much as the devastating effects of CGRP and SP.
The TRPV1 receptor is actively being researched to understand its properties, and in a recent German study it was found that the TRP channel polymorphisms contributed significantly to somatosensory abnormalities of neuropathic pain patients. The shape of the pore determines the neuropathic pain potential more than the TRPV1 itself. The pain patients in the study had a much higher frequency of the polymorphism than the healthy controls).5 It is hypothesized that 20% to 40% of the US population have these polymorphisms that cause the slower healing response, with the result’s being neurogenic pain and inflammation.
What a doctor and patient can expect after an NPT treatment is for 4 hours to 4 days to have complete relief of the pain, then to have improvement of the pain each time the pain returns after the 4 hours to 4 days. This means that if the pain is a 10 out of 10, the expectation is that by the next treatment the pain will be an 8 or 9. With single-area pain syndromes, I expect complete resolution of pain after five to eight treatment sessions. There can be times during the treatment that the pain doesn’t follow the direct descent, but that is not a sign of ineffectiveness of the treatment, and usually after the next visit the descent of pain continues.
There is an art and science to using NPT. While it can be figured out on one’s own, the trainings that Lyftogt provides speeds the practitioner to the most effective ways to treat any pain condition. NPT is simple and beautiful; in the way a spiritual truth can be, the deeper you dive into it, the more profound and simple it is. The science and technique of NPT have now been taught all over the world (NZ, US, Canada, Mexico, Italy, Australia, and Netherlands) to more than 400 doctors. Lyftogt is writing a book that covers all the topics of NPT and hopes to be finished this year.
NPT is easily the most important advance in pain treatment and diagnosis in a long time. It has the potential to become the standard for treatment for pain syndromes in physician’s offices, pain clinics, and emergency rooms.
1. Zochodne D. Neurobiology of Peripheral Nerve Regeneration. Cambridge: Cambridge University Press; 2008:4.
2. Szolcsányi J. Capsaicin-sensitive sensory nerve terminals with local and systemic efferent functions: facts and scopes of an unorthodox neuroregulatory mechanism. Prog Pain Res. 1996;113.
3. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389:816–824.
4. Mosconi T, Kruger L. Fixed-diameter polyethylene cuffs applied to the rat sciatic nerve induce a painful neuropathy: ultra-structural morphometric analysis of axonal alterations. Pain. 1996;64(1):37–57; Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33:87–107.
5. Binder A et al. Transient receptor potential channel polymorphisms are associated with the somatosensory function in neuropathic pain patients. PLoS One. March 2011;6(3):e17387.
For Further Reading
For an excellent historical treatment of peripheral nerve injuries, see Injuries of Nerves and Their Consequences (Philadelphia: J. B. Lippincott; 1872), by American neurologist Silas Weir Mitchell (1829–1914).
Jeff Harris, ND, is a 1992 graduate of Bastyr University. He teaches neural therapy workshops internationally and also teaches medical procedures at Bastyr University. He practices in Greenlake area of Seattle, Washington. For information on workshops and seminars on neural therapy and neural prolotherapy, see his website: www.jeffharrisnd.com.