Chronic Pain Syndrome

Individuals with persistent pain can be diagnosed with Chronic Pain Syndrome and neuropathic pain, which occurs from lesioning of the somatosensory nervous system. This damage leads to functional and structural neuronal changes, such as upregulation of NMDA receptors, loss of descending inhibition, and inflammation within the spinal cord due to activation of immune cells and increased cytokines (Niesters, Martini, & Dahan, 2014). These changes lead to increased pain sensations in affected areas, debilitating individuals with such conditions. Chronic pain patients are often treated based on a trial and error approach with opiods, epileptics, and antidepressants. However, these treatments have low efficacy, with 60-70% of patients reporting inadequate pain relief (Niesters, Martini, & Dahan, 2014).

More recently, pain physicians have started to use low doses of Ketamine to treat pain syndromes, especially disorders with a neuropathic component, such as neuropathic pain from peripheral nerve damage, post-herpetic neuralgia, and complex regional pain syndrome type 1 (Niesters, Martini, & Dahan, 2014). Many patients with CPS are often unsatisfied with their medical regimens, however, recent studies have indicated that Ketamine may be a better treatment for their conditions. A study that considered the long term effects of IV Ketamine observed a large mean effect size in the first week following treatment of 1.22 (95 % confidence interval 0.82 to 1.61, P < 0.001) and in week 4 of 0.39 (95 % confidence interval 0.03 to 0.75, P = 0.036) (Niesters, Martini, & Dahan, 2014). These large effect sizes indicate that Ketamine is an effective treatment for chronic pain, however, that the efficacy of the medication diminishes over time (Niesters, Martini, & Dahan, 2014). In a similar study, Ketamine was shown to reduce pain in individuals with neuropathic, mixed, and non-neuropathic (“nociplastic” or nociceptive) pain. However, effects began to diminish after about 2 weeks (Orhurhu et al., 2019).  Based on the results of both studies, retreatment is required, although it is not clear the exact time frame by which it is most beneficial.

The most likely mechanism through which Ketamine reduces chronic pain is by inhibiting NMDA receptors, blocking afferent transmission of nociceptive signals (Niesters, Martini, & Dahan, 2014). However, Ketamine may also work by increasing descending inhibitory pathways, reducing pain signaling from nociceptive neurons in other regions of the body. A resting state fMRI study found increased activation in the anterior cingulate cortex, orbital frontal cortex, insula, and brainstem of individuals immediately following a low dose Ketamine injection (Niesters, Martini, & Dahan, 2014). These regions are directly involved in descending inhibition and, therefore, Ketamine may succeed in reducing chronic pain by increasing activity within these neural pathways (Niesters, Martini, & Dahan, 2014). Regardless of the mechanism by which Ketamine acts, multiple studies have indicated that Ketamine provides prolonged pain relief, making it a considerable treatment option for patients with CPS.