Functional Inhibition of Occipital Nerve Likely Occurs Within Trigeminocervical Complex

3D render of a man with strong pain in head – Grayscale Image
In a double-blind, placebo-controlled, randomized study, researchers sought to determine the exact site of interaction between the occipital and trigeminal nerves and the mechanisms of this interaction.

Greater occipital nerve (GON) block using lidocaine may aid in the treatment of various headache and facial pain syndromes, and according to study results published in Migraine, the nociceptive activity is likely to occur mainly at the spinal level C2.

Previous studies have supported the benefits of pharmacological block of the GON in patients with cluster headache and trigeminal neuralgia, and this treatment strategy may also be effective against migraine or medication-overuse headache.

The objective of the current study was to determine the exact site of interaction between the occipital and trigeminal nerves and the mechanisms of this interaction.

The double-blind, placebo-controlled, randomized study included 25 healthy volunteers invited to undergo quantitative sensory testing with thermal trigeminal stimuli and stimulus-induced changes in neuronal activity in the brainstem measured using functional MRI techniques.

After completing the Beck Depression Inventory and the German version of the Patient Health Questionnaire to determine for depression, anxiety, and other psychiatric disease, mechanical detection thresholds as well as warm and cold detection and pain thresholds were assessed as a baseline value.

On the second visit, sensory testing was completed to assess detection and pain threshold on each trigeminal branch on both sides. The participants were randomized to receive either lidocaine or placebo on the left GON with a second sensory testing after 10 minutes and MRI scan 30 minutes after the intervention.

At baseline, there were no differences between the groups in mechanical detection thresholds. There were no differences in intensity and unpleasantness rating of the nasal stimulus between GON-block with lidocaine vs placebo treatment.

Pharmacological GON-block with lidocaine had no impact on mechanical detection, thermal detection, or pain thresholds in the face of healthy volunteers. During the subjective assessment of numbness and anesthesia in the ipsilateral occipital region, rates of complete anesthesia were significantly higher in the lidocaine vs the placebo group (92% vs 0%, respectively).

Data from functional MRI indicated that left-sided lidocaine injection was associated with reduced nociceptive neuronal activity in the contralateral trigeminocervical complex, while placebo had no significant impact on nociceptive trigeminal activation.

Based on these findings, the researchers speculated that the site of interaction between the trigeminal and occipital input within the trigeminocervical complex occurs at the level of C2 where the nociceptive signals converge onto the same nuclei, cross to the contralateral side and from there connect to higher brain centers.

One of the limitations of the study was the inability to assess the activation at the level of C2 , due to technical limitation.

“Applying the lidocaine GON-block is likely to reduce the neuronal input originating in the occipital nerve and affect the summary of neuronal activity transmitted to the higher processing centres without affecting the peripheral trigeminal nerve as such,” concluded the researchers.


Hoffmann J, Mehnert J, Koo EM, May A. Greater occipital nerve block modulates nociceptive signals within the trigeminocervical complexJ Neurol Neurosurg Psychiatry. Published online July 26, 2021. doi: 10.1136/jnnp-2021-326433.