The evolution of the definition of pain has evolved due to research and a more comprehensive understanding of etiology. The definition of pain by the International Association for the Study of Pain (IASP) includes “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. Pain is always a personal experience that is influenced to varying degrees by biological, psychological and social factors. Pain cannot be inferred only from activity in sensory neurons. Through their life experiences, individuals learn the concept of pain. A person’s report of an experience as pain should be respected. Although pain usually serves as an adaptive role, it may have adverse effects on function and social and psychological well-being.
The United Nations, World Health Organization and the Journal of the American Medical Association have sounded the alarm about a potential mental health crisis calling it the second pandemic, Covid-19 being the first. Those who contract Covid-19, health care workers on the frontlines, family members of Covid-19 patients are at heightened risk of experiencing severe trauma, posttraumatic stress disorder (PTSD), and depression, not to mention the remainder of our population suffering from social isolation. Evidence supports high rates of co-occurrence PTSD and chronic pain disorders involving an important pathophysiological mechanism called central sensitization (CS).
CS is a significant problem in chronic pain and affects up to 44 million Americans. It is the amplification of neural signaling in the central nervous system (CNS) contributing to hyperalgesia, or increased sensitivity to pain. Rates of psychosocial trauma and lifetime adversity are substantially elevated in patients with pain disorders involving CS, with PTSD prevalence estimated at 20.5% in patients with chronic widespread pain, and those with a trauma history being approximately three times more likely to develop pain conditions involving CS later in life than those without a trauma history. Individuals with trauma histories tend to have worse pain and health outcomes, including more severe symptom presentation, increased disability and likelihood of unemployment, and higher healthcare utilization.
“Wind-up” is defined as a progressively increasing activity in the dorsal horn cells following repetitive activation of primary afferent C-fibers. In humans, temporal summation of repeated painful stimuli has been regarded as a psychophysical correlate of wind-up. Both wind-up and temporal summation appear to be dependent on NMDA receptor activation. The results of clinical trials in patients with chronic pain suggest that the NMDA receptor may represent a new target for modulation of chronic pain.
Ketamine is an NMDA receptor antagonist and an AMPA receptor stimulator. By blocking glutamate reuptake and increasing it in the synapse, ketamine resets the hyperalgesic hyperexcitatory pathway. AMPA stimulation is necessary for increasing brain derived neurotrophic factor (BDNF) which in turn stimulates the formation of new receptors and synapses called synaptogenesis. This process is critical for making connections between neurons and is often severely compromised among those suffering from PTSD and depression. In addition, Ketamine also may reduce signals involved in inflammation.
Ketamine Assisted Psychotherapy (KAP) utilizes a dosage escalation strategy to achieve different levels of consciousness increasing to full out-of-body experiences. We find an individual “sweet spot” with respect to dosage to aid in psychotherapy. Maintenance of the observing self and personal elucidation is fundamental to the success of KAP and dosage selection and results in decrease in symptomatology.
It is important to take into consideration the dose, the set and the setting and have therapists who have worked with the non-ordinary states of consciousness. Preparation prior to a session should address expectations to alleviate fear as well as focus on optimizing lifestyle choices, nutrition, movement, meditation, mindfulness practices. Therapeutic alliance amongst the Therapist, Physician, and Patient is vital as well as having support and being able to facilitate the Integration Process.
Published in July 2019, a meta-analysis was conducted where researchers collected data from multiple randomized control trials and evaluated the efficacy of ketamine infusions in patients with chronic pain. The studies indicated there was a “significant analgesic benefit favoring ketamine.” This meta-analysis also found a positive effect on pain reduction for up to 2 weeks after the ketamine infusions. Apparently, there was no difference between pain types or pain conditions when it came to the measured efficacy of the ketamine infusions. There is evidence suggesting that longer-duration infusions of ketamine provide longer lasting pain relief for patients with chronic neuropathic pain. Increases in the total dose of ketamine administered result in a higher degree of pain relief and possibly greater duration of pain relief.
How can we use ketamine as a catalyst for change and make long lasting improvements?
Cognitive behavioral training focuses on the role of stress in the maintenance of the emotional and physical symptoms, and relaxation, cognitive restructuring and learning problem solving skills are one component. Exercise therapies have a decrease in adherence once supervised programs end, and therefore treatment strategies need to promote ongoing activity, progressively increasing work loads, manageable exercise times and a reasonable number of exercise periods per week. Patients who receive combination therapies are more likely at long-term follow up to have maintained improvements in self efficacy for function.
We believe that a key limitation of available treatments for chronic pain conditions is the failure to directly address trauma and subsequent emotional and relational difficulties therefore only allowing for short term benefit of a medication like ketamine which addressing the underlying CS mechanism. The adverse side effect of ketamine, the dissociation, may actually be the most therapeutic.
Although empirical experience is an important aspect of clinical practice, the lack of clarification of ketamine infusion, intramuscular and oral protocols in the literature calls for comparative effectiveness trials to optimize the degree and duration of pain relief by using a practical and cost-effective protocol. I believe that using intramuscular or oral ketamine with psychotherapy and optimizing lifestyle choices will lead to long lasting pain and antidepressant relief especially in the Fibromyalgia population. Please contact me if you have chronic pain with depression or Fibromyalgia, are interested in feeling well again and want to address the root cause of your surffering.
Intravenous Ketamine Infusions for Neuropathic Pain Management: A Promising Therapy in Need of Optimization. Maher, Dermot P MD, MS; Chen, Lucy MD; Mao, Jianren MD, PhD.
Anesthesia & Analgesia: February 2017 – Volume 124 – Issue 2 – p 661-674
Dr. Michelle Weiner, is an Interventional Pain Management Physician board certified in Physical Medicine and Rehabilitation. She completed her residency and fellowship training at the University of Miami. Her specialty is focused on prevention, treatment, reversal of health deterioration, increasing function and managing pain. Dr. Weiner focuses on diagnosing and treating spine and musculoskeletal pain as well as chronic migraines at the Spine and Wellness Centers of America