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Intradermal Botox To Treat Pain Disorders

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We've all heard a lot about Botox, botulinum toxin type A (BoNTA). It seems as if it's being used for something different every day. There are both cosmetic and medical applications for it. In the right hands, Botox is very helpful; in the wrong hands, it can be disastrous. If you're considering Botox treatments, don't hesitate to ask how much experience your doctor has with Botox administration.

Research into the most effective ways to use Botox for headache and Migraine treatment continues and is promising. Here, we'll take a look at research performed by John Claude Krusz, Ph.D., M.D., and William R. Knoderer, D.D.S., M.D., in Dallas. Please note that this research is based on intradermal (into the skin) administration of Botox. What you're probably used to reading and hearing about is intramuscular (into the muscle) administration of Botox.

It is known that botulinum toxin, type A, (BoNTA) often has marked effects on head pain and other pain. These can outlast effects on motor nerve fibers, and the mechanism may be an effect on nociceptive sensory afferent or non-cholinergic fibers. Intradermal administration was chosen to test this hypothesis for multiple types of painful conditions on the basis that nociceptive fibers are most numerous in the skin and that cutaneous sensory input contribute to these common painful conditions.

A growing body of preliminary data suggests that Botox (BoNTA) may have more widespread effects that pharmacologically go beyond its effects on cholinergic motor nerve fibers. Recent studies have shown that Botox may block or inhibit release of glutamate, CGRP or Substance P from nociceptive neurons1-3. These data may explain, in part, the well-known effect of Botox to reduce pain longer than its ability to reduce muscular problems/deformities.

Krusz and Knoderer previously reported initial success in treating headaches of cervical origin with both Botox and BoNTB4-6. The study referred to in this article extends their initial findings with additional data utilizing intradermal Botox in other painful states. The index case was a patient with CPRS, type 1 (reflex sympathetic dystrophy, aka complex regional pain syndrome), in whom relief of burning pain, swelling and painful radiating symptoms became dramatically better with intradermal Botox.

There were two reasons for choosing intradermal Botox:

  1. It was reasoned that more nociceptive pain fibers were likely to be found in skin and, as importantly, to avoid giving the toxin into motor cholinergic fibers.

  2. In both headache and painful states, it was further reasoned that interference with afferent sensory transmission might contribute to Botox’s analgesic effects.


  • 37 patients with a variety of painful disorders were chosen from a pain and headache practice for treatment with Botox.

  • 19 were female and 18 were male.

  • Average age was 51.7 years (range = 24-73)

  • In all cases; patients were being treated with agents to reduce neuropathic pain or with headache prophylaxis medications, or both. These were tapered in most cases where Botox had reduced pain severity or frequency. Some patients were treated with 25-50 units of Botox; then, it was decided to use a uniform dose of 100 units for each subsequent patient.

  • In all cases, Botox was given intradermally.

  • In the case of painful cervical spasm (and headaches), the skin overlying the greater and lesser occipital nerve inlets was injected (see Figure 1). A skin wheal was raised in 2-3 areas in both sites.

  • In the case of diabetic neuropathy and CRPS, type 1, a digit or digits were injected intradermally proximal to the affected area.

  • In the case of TMJ (temperomandibular joint disorder), a fixed site injection (see Figure 2) was utilized, as we are studying this disorder in an ongoing manner. Carpal tunnel patients were injected intradermally in the region of the volar aspect of the wrist crease (Figure 3).

  • Trigeminal neuralgia patients were injected intradermally on the affected painful side.

Figure 1

Figure 2

Figure 3


  • In the case of painful cervical spasm, all 14 patients treated with intradermal Botox, had reductions in frequency and severity of pain. Average reductions were 85.2% in severity of painful muscle spasm of cervical origin, with an average response time of 9.5 weeks (range 4-21 weeks).

  • In 12 patients with co-existent headaches, there was a 70% reduction in average headache frequency over an average of 8 weeks (range 4-18 weeks). 8 of these patients had prior cervical surgical procedures.

  • 2 of 4 patients treated in the lumbar area responded in terms of reduced back pain.

  • 5 patients with CRPS, type 1, were treated with intradermal Botox. All 5 responded with reduced burning and allodynia, as well reduced swelling.

  • 2 cases of diabetic neuropathy were treated with excellent response, although in 1 case re-treatment did not match prior results. Toe dystonia was markedly improved on both occasions.

  • 5 cases of persistent median nerve entrapment pain were treated. 3 had undergone prior nerve release surgery. All 5 responded with reduction in painful symptoms.

  • 3 cases of temporomandibular disorder (TMD) were also treated with reductions in jaw pain, popping, bruxism, clenching and muscle pain in all 3 treated subjects.

  • Average pain reductions in responders was 8.5 weeks in duration (range 3-20 weeks), with an average reduction of 68% in pain symptoms across all categories of patients.


  • Botulinum toxin, type A, given intradermally, shows a marked ability to reduce painful symptoms in many different pain states, some not studied clinically.

  • It also has excellent efficacy in treating painful cervical spasm.

  • These results compare very favorably, or are better than, results from usual intramuscular administration of Botox.

  • This open-label data raises many questions about mechanism(s) of action of Botox, particularly in the central nervous system, including uptake into nociceptive fibers and transport to the dorsal horn of the spinal cord. Blockade of pain transmission at central facilitative sites may occur, and this, in turn, reduces pain transmission in various pain states.

  • Double-blind studies are definitely warranted to replicate these findings.


This is very promising research for anyone with headaches, Migraine, or any of the other conditions treated in this trial. Intradermal administration of Botox is less painful than intramuscular and, in this study, compared quite well with the intramuscular administration. We should be seeing results of double-blind studies on this application in the near future.

To view a copy of the poster presentation of this study presented to the annual conference of the American Pain Society and to the European Federation of Neurological Societies conference, please click HERE.

by John Claude Krusz, Ph.D., M.D.
and Teri Robert

November 18, 2005


Krusz, John Claude, Ph.D., M.D.; Knoderer, William R., D.D.S., M.D. "Intradermal Botulinum Toxin Type A: To Treat Pain Disorders." Poster presentation to the annual conference of the American Pain Society, Boston, March, 2005; and to the European Federation of Neurological Societies conference, Athens, Greece, September, 2005.


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