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
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
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
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
motor nerve fibers. Recent studies have shown that Botox may block or inhibit
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
There were two reasons for choosing intradermal Botox:
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.
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
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
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
neuropathy and CRPS, type 1, a digit or digits were injected intradermally
proximal to the affected area.
In the case of
(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.
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
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.
also has excellent efficacy in treating painful cervical spasm.
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
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,
2005; and to the European Federation of Neurological Societies conference,
Athens, Greece, September, 2005.