Cranial parasympathetic activation induces autonomic symptoms but no cluster headache attacks

Cephalalgia. 2018 Jul;38(8):1418-1428. doi: 10.1177/0333102417738250. Epub 2017 Oct 30.


Background Low frequency (LF) stimulation of the sphenopalatine ganglion (SPG) may increase parasympathetic outflow and provoke cluster headache (CH) attacks in CH patients implanted with an SPG neurostimulator. Methods In a double-blind randomized sham-controlled crossover study, 20 CH patients received LF or sham stimulation for 30 min on two separate days. We recorded headache characteristics, cephalic autonomic symptoms (CAS), plasma levels of parasympathetic markers such as pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal peptide (VIP), and mechanical detection and pain thresholds as a marker of sensory modulation. Results In the immediate phase (0-60 min), 16 (80%) patients experienced CAS after LF stimulation, while nine patients (45%) reported CAS after sham ( p = 0.046). We found no difference in induction of cluster-like attacks between LF stimulation (n = 7) and sham stimulation (n = 5) ( p = 0.724). There was no difference in mechanical detection and pain thresholds, and in PACAP and VIP plasma concentrations between LF and sham stimulation ( p ≥ 0.162). Conclusion LF stimulation of the SPG induced autonomic symptoms, but no CH attacks. These data suggest that increased parasympathetic outflow is not sufficient to induce CH attacks in patients. Study protocol registration number NCT02510729.

Keywords: Cluster headache; autonomic nervous system; headache model; neurostimulation; sphenopalatine ganglion.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autonomic Pathways / physiopathology*
  • Cluster Headache / physiopathology*
  • Cluster Headache / therapy*
  • Cross-Over Studies
  • Double-Blind Method
  • Electric Stimulation Therapy*
  • Electrodes, Implanted
  • Female
  • Ganglia, Parasympathetic / physiology
  • Humans
  • Male
  • Middle Aged
  • Pterygopalatine Fossa / innervation

Associated data