The cingulum: a central hotspot for the battle against chronic intractable pain?

Chronic pain causes a major burden on patient's lives, in part due to its profound socioeconomic impact. Despite the development of various pharmacological approaches and (minor) invasive treatments, a subset of patients remain refractory, hence why alternative targeted neurosurgical interventions like cingulotomy and deep brain stimulation of the anterior cingulate cortex should be considered in the last resort. Despite clinical evidence supporting the potential of these treatments in the management of chronic intractable pain, physicians remain reluctant on its clinical implementation. This can be partially attributed to the lack of clear overviews summarizing existent data. Hence, this article aims to evaluate the current status of cingulotomy and deep brain stimulation of the anterior cingulate cortex in the treatment of chronic intractable pain, to provide insight in whether these neurosurgical approaches and its target should be reconsidered in the current era. In the current study, a literature searches was performed using the PubMed database. Additional articles were searched manually through reviews or references cited within the articles. After exclusion, 24 and 5 articles remained included in the analysis of cingulotomy and deep brain stimulation of the anterior cingulate cortex, respectively. Results indicate that various surgical techniques have been described for cingulotomy and deep brain stimulation of the anterior cingulate cortex. Cingulotomy is shown to be effective 51-53% and 43-64% of patients with neoplastic and non-neoplastic pain at ≤6 months follow-up, and 82% (9/11) and 76% (90/118) at ≥ 12months follow-up, respectively. With regard to deep brain stimulation of the anterior cingulate cortex, no data on neoplastic pain was reported, however, 59% (10/17) and 57% (8/14) of patients with non-neoplastic pain were considered responders at ≤ 6 months and ≥ 12months follow-up, respectively. The most reported adverse events include change in affect (>6.9%, >29/420) and confusion (>4.8%, >20/420) for cingulotomy, and infection (12.8%, 6/47), seizures (8.5%, 4/47) and decline in semantic fluency (6.4%, 3/47) for deep brain stimulation of the anterior cingulate cortex. It can be concluded that cingulotomy and deep brain stimulation of the anterior cingulate cortex are effective last resort strategies for patients with refractory non-neoplastic and neoplastic pain, especially in case of an affective emotional component. Future research should be performed on the cingulum as a neurosurgical target as it allows for further exploration of promising treatment options for chronic intractable pain.