This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
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
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Disputes & Debates: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.