Botulinum Toxin A in the Treatment of Chronic Tension-Type Headache With Cervical Myofascial Trigger Points: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

Authors

  • R. Norman Harden MD,

    1. From the Center for Pain Studies, Rehabilitation Institute of Chicago, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, B. Tann, P. Joseph, and T.S. Lee); Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, P. Joseph, and T.S. Lee); Department of Psychology, University of Mississippi, Oxford, MS, USA (T.A. Smitherman); Department of Anesthesiology, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA (T.T. Houle).
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  • Jerod Cottrill DO,

    1. From the Center for Pain Studies, Rehabilitation Institute of Chicago, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, B. Tann, P. Joseph, and T.S. Lee); Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, P. Joseph, and T.S. Lee); Department of Psychology, University of Mississippi, Oxford, MS, USA (T.A. Smitherman); Department of Anesthesiology, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA (T.T. Houle).
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  • Christine M. Gagnon PhD,

    1. From the Center for Pain Studies, Rehabilitation Institute of Chicago, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, B. Tann, P. Joseph, and T.S. Lee); Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, P. Joseph, and T.S. Lee); Department of Psychology, University of Mississippi, Oxford, MS, USA (T.A. Smitherman); Department of Anesthesiology, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA (T.T. Houle).
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  • Todd A. Smitherman PhD,

    1. From the Center for Pain Studies, Rehabilitation Institute of Chicago, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, B. Tann, P. Joseph, and T.S. Lee); Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, P. Joseph, and T.S. Lee); Department of Psychology, University of Mississippi, Oxford, MS, USA (T.A. Smitherman); Department of Anesthesiology, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA (T.T. Houle).
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  • Stephan R. Weinland PhD,

    1. From the Center for Pain Studies, Rehabilitation Institute of Chicago, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, B. Tann, P. Joseph, and T.S. Lee); Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, P. Joseph, and T.S. Lee); Department of Psychology, University of Mississippi, Oxford, MS, USA (T.A. Smitherman); Department of Anesthesiology, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA (T.T. Houle).
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  • Beverley Tann RN,

    1. From the Center for Pain Studies, Rehabilitation Institute of Chicago, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, B. Tann, P. Joseph, and T.S. Lee); Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, P. Joseph, and T.S. Lee); Department of Psychology, University of Mississippi, Oxford, MS, USA (T.A. Smitherman); Department of Anesthesiology, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA (T.T. Houle).
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  • Petra Joseph MD,

    1. From the Center for Pain Studies, Rehabilitation Institute of Chicago, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, B. Tann, P. Joseph, and T.S. Lee); Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, P. Joseph, and T.S. Lee); Department of Psychology, University of Mississippi, Oxford, MS, USA (T.A. Smitherman); Department of Anesthesiology, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA (T.T. Houle).
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  • Thomas S. Lee MD,

    1. From the Center for Pain Studies, Rehabilitation Institute of Chicago, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, B. Tann, P. Joseph, and T.S. Lee); Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, P. Joseph, and T.S. Lee); Department of Psychology, University of Mississippi, Oxford, MS, USA (T.A. Smitherman); Department of Anesthesiology, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA (T.T. Houle).
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  • Timothy T. Houle PhD

    1. From the Center for Pain Studies, Rehabilitation Institute of Chicago, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, B. Tann, P. Joseph, and T.S. Lee); Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA (R.N. Harden, J. Cottrill, C.M. Gagnon, S.R. Weinland, P. Joseph, and T.S. Lee); Department of Psychology, University of Mississippi, Oxford, MS, USA (T.A. Smitherman); Department of Anesthesiology, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA (T.T. Houle).
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  • Conflict of Interest: R. Norman Harden has received a research grant from UCB, a research grant and serves on the advisory boards of Endo Pharmaceuticals and GlaxoSmithKline, and is a consultant for Solstice Neurosciences. Timothy T. Houle has received an unrestricted research grant from Endo Pharmaceuticals.

R. Norman Harden, Rehabilitation Institute of Chicago, Center for Pain Studies, 446 E. Ontario, Suite 1011, Chicago, IL 60611, USA.

Abstract

Objective.— To evaluate the efficacy of botulinum toxin A (BT-A) as a prophylactic treatment for chronic tension-type headache (CTTH) with myofascial trigger points (MTPs) producing referred head pain.

Background.— Although BT-A has received mixed support for the treatment of TTH, deliberate injection directly into the cervical MTPs very often found in this population has not been formally evaluated.

Methods.— Patients with CTTH and specific MTPs producing referred head pain were assigned randomly to receive intramuscular injections of BT-A or isotonic saline (placebo) in a double-blind design. Daily headache diaries, pill counts, trigger point pressure algometry, range of motion assessment, and responses to standardized pain and psychological questionnaires were used as outcome measures; patients returned for follow-up assessment at 2 weeks, 1 month, 2 months, and 3 months post injection. After 3 months, all patients were offered participation in an open-label extension of the study. Effect sizes were calculated to index treatment effects among the intent-to-treat population; individual time series models were computed for average pain intensity.

Results.— The 23 participants reported experiencing headache on a near-daily basis (average of 27 days/month). Compared with placebo, patients in the BT-A group reported greater reductions in headache frequency during the first part of the study (P = .013), but these effects dissipated by week 12. Reductions in headache intensity over time did not differ significantly between groups (P = .80; maximum d = 0.13), although a larger proportion of BT-A patients showed evidence of statistically significant improvements in headache intensity in the time series analyses (62.5% for BT-A vs 30% for placebo). There were no differences between the groups on any of the secondary outcome measures.

Conclusions.— The evidence for BT-A in headache is mixed, and even more so in CTTH. However, the putative technique of injecting BT-A directly into the ubiquitous MTPs in CTTH is partially supported in this pilot study. Definitive trials with larger samples are needed to test this hypothesis further.

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