Pathophysiology of pain

The province of medicine is to preserve and restore health and to relieve suffering. Understanding pain is essential to both of these goals. Because pain is universally understood as a signal of disease ít is the most common symptom that brings a patient to a physician's attention. The fuction of the pain sensory system is to protect the body and maintain homeostasis. It does this by detecting, localizing, and identifying potential or actual tissue-damaging processes. Because different diseases produce characteristic patterns of tissue damage, the quality, time course, and location of a patient's pain lend important diagnostic clues. It is the physician's responsibility to provide rapid and effctive pain relief.

The pain sensory system

Pain is an unpleasant sensation localized to a part of the body. It is often described in terms of a penetrating or tissue-destructive process (e.g. stabbing, burning, twisting, tearing, squeezing) and/or of a bodily or emotional reaction (terrifyng, nauseating, sickening). Furthermore, any pain of moderate or higher intensity is accompanied by anxiety and the urge to escape or terminate the feeling. These properties illustrate the duality of pain: it is both sensation and emotion. When it is acute, pain is characteristically associated with behavioral arousal and a stress response consisting of increased blood pressure, heart rate,  pupil diameter, and plasma cortisol levels. In addition, local muscle  contraction (e.g. limb flexion, abdominal wall rigidity) is often present.

Classification of Pain

Classification of pain: Classifying pain is helpful to guide assessment and treatment. There are many ways to classify pain and classifications may overlap. The common types of pain include:

  • Nociceptive: represents the normal response to noxious insult or injury of tissues such as skin, muscles, visceral organs, joints, tendons, or bones.
    • Examples include:
      • Somatic: musculoskeletal (joint pain, myofascial pain), cutaneous; often well localized
      • Visceral: hollow organs and smooth muscle; usually referred
  • Neuropathic: pain initiated or caused by a primary lesion or disease in the somatosensory nervous system.
    • Sensory abnormalities range from deficits perceived as numbness to hypersensitivity (hyperalgesia or allodynia), and to paresthesias such as tingling.
    • Examples include, but are not limited to, diabetic neuropathy, postherpetic neuralgia, spinal cord injury pain, phantom limb (post-amputation) pain, and post-stroke central pain.
  • Inflammatory: a result of activation and sensitization of the nociceptive pain pathway by a variety of mediators released at a site of tissue inflammation.
    • The mediators that have been implicated as key players are proinflammatory cytokines such IL-1-alpha, IL-1-beta, IL-6 and TNF-alpha, chemokines, reactive oxygen species, vasoactive amines, lipids, ATP, acid, and other factors released by infiltrating leukocytes, vascular endothelial cells, or tissue resident mast cells
    • Examples include appendicitis, rheumatoid arthritis, inflammatory bowel disease, and herpes zoster.

Clinical Implications of classification: Pathological processes never occur in isolation and consequently more than one mechanism may be present and more than one type of pain may be detected in a single patient; for example, it is known that inflammatory mechanisms are involved in neuropathic pain.

  • There are well-recognized pain disorders that are not easily classifiable. Our understanding of their underlying mechanisms is still rudimentary though specific therapies for those disorders are well known; they include cancer pain, migraine and other primary headaches and wide-spread pain of thefibromyalgia type.

Pain Intensity: Can be broadly categorized as: mild, moderate and severe. It is common to use a numeric scale to rate pain intensity where 0 = no pain and 10 is the worst pain imaginable:

  • Mild: <4/10
  • Moderate: 5/10 to 6/10
  • Severe: >7/10

Time course: Pain duration

  • Acute pain: pain of less than 3 to 6 months duration
  • Chronic pain: pain lasting for more than 3-6 months, or persisting beyond the course of an acute disease, or after tissue healing is complete.
  • Acute-on-chronic pain: acute pain flare superimposed on underlying chronic pain.


In clinical practice, ozone injections have a high frequency of success in treating joint pain. Indeed, clinical reports abound of patients who were scheduled for joint replacement surgery and ended up postponing it because of complete or acceptable symptom amelioration from ozone treatment. Knee and shoulder joints appear to be the most responsive joints to treatment, while hip joints are the most challenging to treat successfully, even with the assistance of ultrasound guidance.

Dental pain also tends to respond well to treatment, whether it is post-root canal, trauma-induced, or idiopathic. I have observed trigger points and symptom-inducing scar tissue to regularly resolve more easily when ozone is added into the treatment protocol. Nasal inhalation of ozone gas that has been percolated through olive oil frequently works very well for pain from acute or chronic sinusitis (it must be noted that if ozone is inhaled without percolating it in oil, it is very irritating and damaging to the lungs30). Patients suffering from chronic infections such as Lyme or its coinfections (eg, Bartonella, Erlichia, Babesia, etc) often have faster symptom resolution when using ozone injections in painful muscles or joints. Such amelioration may be due to a combination of the anti-inflammatory effects of ozone and its antimicrobial properties.
Systemic administration of ozone, as in major autohemotherapy, can be of great benefit in chronic pain syndromes like fibromyalgia, chronic fatigue syndrome, autoimmune disorders, etc. In some cases, MAH as a standalone treatment can provide symptom relief; however, in the majority of cases, additional interventions are required. Given that the proposed mechanisms of MAH revolve around the enhancement of antioxidant status, mitochondrial function, and immunomodulation, it stands to reason that supportive dietary and lifestyle changes, supplements, and other therapies would be required to enhance its effects. Indeed, the effects of MAH rarely reach their full potential without the following: an anti-inflammatory diet, exercise to tolerance, adequate nutrient status (especially B vitamins, magnesium, mitochondrial support factors), endocrine support (thyroid, adrenals, etc), unimpeded liver function and emunctories, and support towards a healthy milieu (ie, balanced microbes, pH, autonomic function, mental/emotional state, methylation, etc). In short, systemic ozone therapy can be a powerful complement to what we already specialize in as naturopathic doctors.

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