Letter to the Editor: Gate control pain modulation theory explains the effectiveness of prolotherapy

E-letter by:
Dr. Stavros Saripanidis, Consultant in Obstetrics and Gynaecology, Private Surgery, Thessaloniki, Greece
In response to:

Simon Petrides. 2011. The use of prolotherapy injections for elite athletes. Br J Sports Med ; 45: 2 (Electronic pages).

Photo of 'Spine' in Millennium Square, Bristol by Davecpayne, Flickr cc

Dear BJSM Editors,

The dorsal horns are not merely passive transmission stations but sites at which dynamic activities (inhibition, excitation and modulation) occur. [18]

Via a series of filters and amplifiers, the nociceptive message is integrated and analysed in the cerebral cortex, with interconnections with various areas. [1]

The processing of pain takes place in an integrated matrix throughout the neuroaxis and occurs on at least three levels, at peripheral, spinal, and supraspinal sites. [9]

Knowledge of the modalities of pain control is essential to correctly adapt treatment strategies (drugs, neurostimulation, psycho-behavioural therapy, etc.).

Dysfunction of pain control systems causes neuropathic pain. [1]

Spinal Cord Stimulation modalities evolved from the gate-control theory postulating a spinal modulation of noxious inflow.   [16] [2] [7] [11] [12] [15] [17] [20] [22] [23] [24] [25] [26]

It has been demonstrated in multiple studies that dorsal horn neuronal activity caused by peripheral noxious stimuli could be inhibited by concomitant stimulation of the dorsal columns. [8]

Pain relief was more prominent at pain ascending through C fibers than pain ascending through Adelta fibers. [21]

Many theories on the mechanism of action of Spinal Cord Stimulation have been suggested, including activation of gate control mechanisms, conductance blockade of the spinothalamic tracts, activation of supraspinal mechanisms, blockade of supraspinal sympathetic mechanisms, and activation or release of putative neuromodulators.  [14]

At present, Spinal Cord Stimulation is a well established form of treatment for failed back surgery syndrome, complex regional pain syndromes (CRPS), low back pain with radiculopathy and refractory pain due to ischemia. [4] [3] [8] [13]

Stimulation produced analgesia can provide a level of analgesia and efficacy that is unattainable by other treatment modalities. [19]

Spinal Cord Stimulation for the treatment of chronic pain is cost-effective when used in the context of a pain treatment continuum. [14]

Precise subcutaneous field stimulation is targeted to specific areas of neuropathic pain. [6]

We aim at attenuation or blockade of pain through intervention at the periphery, by activation of inhibitory processes that gate pain at the spinal cord and brain. [9]

Segmental noxious stimulation produces a stronger analgesic effect than segmental innocuous stimulation. [10]

That is exactly what intradermal sterile water injections do!

This therapeutic approach should not be limited only to elite athletes.

It can work for every patient with back pain.


[1] Prog Urol. 2010 Nov;20(12):843-52. Epub 2010 Oct 20. Anatomy and physiology of chronic pelvic and perineal pain. Labat JJ, Robert R, Delavierre D, Sibert L, Rigaud J. Centre federatif de pelviperineologie, clinique urologique, CHU Hotel-
Dieu, 1, place Alexis-Ricordeau, 44093 Nantes, France.

[2] Int J Rehabil Res. 2010 Sep;33(3):211-7. Effect of transcutaneous electrical nerve stimulation on sensation thresholds in patients with painful diabetic neuropathy: an observational study. Moharic M, Burger H. Department of Physical and Rehabilitation Medicine, Linhartova 51, SI-1000Ljubljana, Slovenia.

[3] Conf Proc IEEE Eng Med Biol Soc. 2009;2009:2033-6. Spinal cord stimulation for complex regional pain syndrome. Shrivastav M, Musley S.Medtronic Neuromodulation, 7000 Central Ave NE, Minneapolis, Minnesota, 55432 USA.

[4] J Clin Monit Comput. 2009 Oct;23(5):333-9. Spinal cord stimulation: principles of past, present and future practice: a review. Kunnumpurath S, Srinivasagopalan R, Vadivelu N. St George's School of Anaesthesia, Tooting, London, UK.

[5] Brain Res Rev. 2009 Apr;60(1):149-70. Epub 2008 Dec 31.Chloride regulation in the pain pathway. Price TJ, Cervero F, Gold MS, Hammond DL, Prescott SA.
University of Arizona, Department of Pharmacology, USA.

[6] Curr Pain Headache Rep. 2008 Jan;12(1):28-31. Peripheral nerve stimulation for chronic pain.Henderson JM.Stereotactic and Functional Neurosurgery, Stanford University School of Medicine, 300 Pasteur Drive, Edwards Building/R-227, Stanford, CA 94305, USA.

[7] Schmerz. 2007 Aug;21(4):307-10, 312-7. From Descartes to fMRI. Pain theories and pain concepts.Handwerker HO.Institut fur Physiologie und Pathophysiologie, Universitat Erlangen/Nurnberg, Deutschland.

[8] Pain Physician. 2002 Apr;5(2):156-66. Spinal cord stimulation.
Stojanovic MP, Abdi S.Interventional Pain Program, MGH Pain Center, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School,
Cambridge, MA 02135, USA.

[9] J Bone Joint Surg Am. 2006 Apr;88 Suppl 2:58-62.Basic science of pain.
DeLeo JA. Dartmouth-Hitchcock Medical Center, Dartmouth Medical School, Neuroscience
Center at Dartmouth, Department of Anesthesiology, Lebanon, NH 03756, USA.

[10] Pain. 2005 May;115(1-2):152-60. Segmental noxious versus innocuous electrical stimulation for chronic pain relief and the effect of fading sensation during treatment. Defrin R, Ariel E, Peretz C. Department of Physical Therapy, School of Allied Health Professions, Sackler Faculty of Medicine, Tel-Aviv University, 69978 Ramat Aviv, Israel.

[11] Annu Rev Neurosci. 2003;26:1-30. Epub 2003 Mar 6. Pain mechanisms: labeled lines versus convergence in central processing. Craig AD. Atkinson Pain Research Laboratory, Barrow Neurological Institute, 350 W.Thomas Road, Phoenix, AZ 85013, USA.

[12] Sports Med. 2002;32(4):251-67. Return-to-work interventions for low back pain: a descriptive review of contents and concepts of working mechanisms. Staal JB, Hlobil H, van Tulder MW, K?ke AJ, Smid T, van Mechelen W.Department of Social Medicine and Research Centre on Work, Physical Activity and Health, VU University Medical Center, Van der Boechorststraat 7, Amsterdam, The Netherlands.

[13] Curr Pain Headache Rep. 2001 Apr;5(2):130-7.Stimulation methods for neuropathic pain control. Stojanovic MP. MGH Pain Center, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA 02114, USA.

[14] Curr Rev Pain. 1999;3(6):419-426. Spinal Cord Stimulation: Indications, Mechanism of Action, and Efficacy. Krames E. Pacific Pain Treatment Centers, 2000 Van Ness Avenue, Suite 402, San Francisco, CA 94109, USA.

[15] Ann Pharm Fr. 2000 Mar;58(2):77-83. Pain and its main transmitters.Costentin J.Unite de Neuropsychopharmacologie Experimentale, ESA 6036 CNRS, Institut Federatif de Recherches Multidisciplinaires sur les Peptides=IFR 23, Faculte de Medecine et Pharmacie, 22, bd Gambetta, F 76000 Rouen.

[16] Neurol Res. 2000 Apr;22(3):285-92.Mechanisms of spinal cord stimulation in neuropathic pain. Meyerson BA, Linderoth B. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.

[17] Pain. 1999 Aug;Suppl 6:S149-52.Regulation of spinal nociceptive processing: where we went when we wandered onto the path marked by the gate. Yaksh TL.Department of Anesthesiology, University of California, San Diego, USA.

[18] Pain. 1999 Aug;Suppl 6:S121-6. From the gate to the neuromatrix. Melzack R. Department of Psychology, McGill University, Montreal, Quebec, Canada.

[19] J Clin Neurophysiol. 1997 Jan;14(1):46-62. Stimulation of the central and peripheral nervous system for the control of pain. Stanton-Hicks M, Salamon J. Anaesthesia Pain Management Center, Cleveland Clinic Foundation, OH 44195, USA.

[20] Percept Psychophys. 1996 Jul;58(5):693-703. An investigation of the gate control theory of pain using the experimental pain stimulus of potassium iontophoresis.
Humphries SA, Johnson MH, Long NR. Department of Psychology, Massey University, Palmerston North, New Zealand.

[21] J Peripher Nerv Syst. 1996;1(3):189-98. Pain relief by various kinds of interference stimulation applied to the peripheral skin in humans: pain-related brain potentials following CO2 laser stimulation. Kakigi R, Watanabe S. Department of Integrative Physiology, National Institute for Physiological Sciences, Okazaki, Japan.

[22] Nurs Stand. 1993 Jul 28-Aug 3;7(45):25-7. Pain: opening up the gate control theory. Davis P.

[23] Bull Acad Natl Med. 1989 Oct;173(7):855-60; discussion 860-1.Gate control of the nociceptive message: applications to the treatment of pain. Cambier J.

[24] Brain Res. 1983 Dec 5;280(2):217-31. Thalamic nucleus ventro-postero-lateralis inhibits nucleus parafascicularis response to noxious stimuli through a non-opioid pathway. Benabid AL, Henriksen SJ, McGinty JF, Bloom FE.

[25] Psychosom Med. 1979 Mar;41(2):101-8. A signal detection analysis of the effects of transcutaneous stimulation on pain. Malow RM, Dougher MJ.

[26] GATE CONTROL OF ION FLUX IN AXONS. GOLDMAN DE. J Gen Physiol. 1965 May;48:SUPPL:75-7.

Conflict of Interest: None declared

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