Background: Gabapentin is an effective therapeutic alternative for chronic low back pain, indicated in several guidelines for treating neuropathic pain as first-line medication. This study aimed to describe the pharmacodynamics of gabapentin in the central nervous system of patients with chronic low back pain (CLBP) by using single-photon emission CT (SPECT) with [99mTc]Tc-ECD. Methods: We selected 13 patients with CLBP due to lumbar disc herniation. They underwent SPECT before and after using gabapentin, compared with a SPECT database of healthy volunteers. A second analysis compared regional cerebral blood flow (rCBF) changes between responders and non-responders to gabapentin and the healthy controls. Results: The mean age of patients was 41 years, and the mean pain intensity was 5.92 points, measured by the Numeric Rating Scale. After using gabapentin, SPECT showed an increase of rCBF in the bilateral anterior cingulate gyrus and a decrease of rCBF in periaqueductal gray matter. Non-responder patients with gabapentin showed a post-treatment decrease of rCBF in the paracentral lobule of the brain. Conclusions: A lack of improvement in some patients with gabapentin may be associated with an activated affective circuit of pain, evidenced by the increase of rCBF of the anterior cingulate cortex. A maladaptive brain state in chronic pain can explain the decrease of rCBF in the default mode network structures. Gabapentin acts directly or indirectly on neurons of periaqueductal gray substance by increasing the pain threshold and decreasing the rCBF of this structure