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Abstract
Objective To characterize the functional brain changes involved in δ-9-tetrahydrocannabinol (THC) modulation of chronic neuropathic pain.
Methods Fifteen patients with chronic radicular neuropathic pain participated in a randomized, double-blind, placebo-controlled trial employing a counterbalanced, within-subjects design. Pain assessments and functional resting state brain scans were performed at baseline and after sublingual THC administration. We examined functional connectivity of the anterior cingulate cortex (ACC) and pain-related network dynamics using graph theory measures.
Results THC significantly reduced patients' pain compared to placebo. THC-induced analgesia was correlated with a reduction in functional connectivity between the anterior cingulate cortex (ACC) and the sensorimotor cortex. Moreover, the degree of reduction was predictive of the response to THC. Graph theory analyses of local measures demonstrated reduction in network connectivity in areas involved in pain processing, and specifically in the dorsolateral prefrontal cortex (DLPFC), which were correlated with individual pain reduction.
Conclusion These results suggest that the ACC and DLPFC, 2 major cognitive-emotional modulation areas, and their connections to somatosensory areas, are functionally involved in the analgesic effect of THC in chronic pain. This effect may therefore be mediated through induction of functional disconnection between regulatory high-order affective regions and the sensorimotor cortex. Moreover, baseline functional connectivity between these brain areas may serve as a predictor for the extent of pain relief induced by THC.
Glossary
- ACC=
- anterior cingulate cortex;
- aMCC=
- anterior middle cingulate cortex;
- ALE=
- activation likelihood estimate;
- BOLD=
- blood oxygenation level–dependent;
- BP=
- blood pressure;
- DLPFC=
- dorsolateral prefrontal cortex;
- FDR=
- false discovery rate;
- FOV=
- field of view;
- HR=
- heart rate;
- MCC=
- middle cingulate cortex;
- MNI=
- Montreal Neurological Institute;
- ROI=
- region of interest;
- SII=
- secondary somatosensory cortex;
- STAI-S=
- State-Trait Anxiety Inventory–State;
- TE=
- echo time;
- THC=
- δ-9-tetrahydrocannabinol;
- TR=
- repetition time;
- VAS=
- visual analog scale
Footnotes
↵* These authors contributed equally to this work as first authors.
↵‡ These authors contributed equally to this work as last authors.
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received April 3, 2018.
- Accepted in final form June 29, 2018.
- © 2018 American Academy of Neurology
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