Controversial Drug May Address Co-Occurring Complex Regional Pain Syndrome and PTSD

SAN ANTONIO—Post-traumatic stress disorder (PTSD) is highly prevalent in the United States military forces, with rates as high as 31% and 20% for Vietnam War and Operation Iraqi Freedom (OIF) veterans, respectively.¹ An estimated 50% of patients diagnosed with PTSD also present with chronic pain.²

In armed forces involved in OIF and Operation Enduring Freedom, fractures and extremity wounds represented 54% of all wounds, and 47% of these patients went on to develop chronic pain.³ Distal extremity trauma and fractures constitute the 2 most common precipitating events for Complex Regional Pain Syndrome II (CRPS).⁴

Benjamin M. Keizer, PhD, a pain psychologist at San Antonio Military Medical Center who encounters numerous patients with co-occurring CRPS and PTSD, presented evidence of a successful treatment for these individuals at the American Academy of Pain Management’s Annual Meeting.⁵

Although PTSD is challenging to diagnose, Dr Keizer found that the presence of nightmares, avoidance, depression, and substance abuse in veterans are oftentimes indicative of the disorder, which requires professional help.

CRPS is characterized by a varied and dynamic clinical presentation and a regional distribution of symptoms. No “gold-standard” diagnostic test is available for CRPS, and according to Dr Keizer, an ideal treatment for this condition requires a multi-disciplinary approach.

Dr Keizer presented a case in which all treatments, including high dose opioids and hydrocodone, spinal cord stimulation, and physical therapy had failed in a patient presenting with lower extremity CRPS type II, lower back pain, and PTSD. Ketamine infusion successfully treated CRPS and PTSD in this and 6 other patients (25 to 65 years of age, male and female, with sexual and/or combat trauma), whom Dr Keizer followed.

Because of the sheer nature of ketamine, it is essential to initially educate patients about this schedule III controlled substance, said Dr Keizer. Ketamine is a potent analgesic which provokes hallucinations; its binding to N-Methyl-D-Aspartate (NMDA) receptors mediates effects of the drug on fear learning and extinction as well as memory.⁶ In Dr Keizer’s experience, following ketamine infusion, patients “are able to remember what happened in more detail, except with less fear, which is a key issue.”

A combination of ketamine infusion treatment and psychotherapy was found to attenuate PTSD manifestation to a level below diagnosis threshold after 4 infusion sessions and to reduce pain scores by the third session. The efficacy of the ketamine treatment for both PTSD and CRPS may be explained by neural circuits common to both conditions.⁷

In addition, it is hypothesized that ketamine infusion, by facilitating retrieval of the traumatic memory and reducing central sensitization through down-regulation of activity in the prefrontal cortex, enhances extinction of memories previously paired with pain.

According to Dr Keizer, “an evidence-based PTSD psychotherapy with a patient on ketamine would set the conditions for enhanced modification of core maladaptive fears underlying PTSD and fear/avoidance thoughts and behaviors that sustain both PTSD and CRPS following ketamine infusion.”

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References

1. National Center for PTSD. US Department of Veterans Affairs. Available at: http://www.ptsd.va.gov/. Accessed September 25, 2016.
2. Starr AJ, Smith WR, Frawley WH, et al. Symptoms of posttraumatic stress disorder after orthopaedic trauma. J Bone Joint Surg Am. 2004;86-A(6):1115-1121.
3. Cross JD, Wenke JC, Ficke JR, Johnson AE. Data-driven disaster management requires data: implementation of a military orthopaedic trauma registry. J Surg Orthop Adv. 2011;20(1):56-61.
4. De Mos M, De Bruijn AG, Huygen FJ, Dieleman JP, Stricker BH, Sturkenboom MC. The incidence of complex regional pain syndrome: a population-based study. Pain. 2007;129(1-2):12-20.
5. Keizer B. Interdisciplinary Treatment for the War on Comorbid CRPS and PTSD. Presented at: AAPM 2016. September 21-25, 2016; San Antonio, TX. 
6. Abdallah CG, Sanacora G, Duman RS, Krystal JH. Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics. Annu Rev Med. 2015;66:509-523.
7. Scioli-Salter ER, Forman DE, Otis JD, Gregor K, Valovski I, Rasmusson AM. The shared neuroanatomy and neurobiology of comorbid chronic pain and PTSD: therapeutic implications. Clin J Pain. 2015;31(4):363-374.