TY - JOUR

T1 - Cranial parasympathetic activation induces autonomic symptoms but no cluster headache attacks

AU - Guo, Song

AU - Petersen, Anja Sofie

AU - Schytz, Henrik Winther

AU - Barløse, Mads

AU - Caparso, Anthony

AU - Fahrenkrug, Jan

AU - Jensen, Rigmor Højland

AU - Ashina, Messoud

PY - 2018

Y1 - 2018

N2 - 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 ClinicalTrials.gov registration number NCT02510729.

AB - 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 ClinicalTrials.gov registration number NCT02510729.

KW - Adult

KW - Aged

KW - Autonomic Pathways/physiopathology

KW - Cluster Headache/physiopathology

KW - Cross-Over Studies

KW - Double-Blind Method

KW - Electric Stimulation Therapy

KW - Electrodes, Implanted

KW - Female

KW - Ganglia, Parasympathetic/physiology

KW - Humans

KW - Male

KW - Middle Aged

KW - Pterygopalatine Fossa/innervation

U2 - 10.1177/0333102417738250

DO - 10.1177/0333102417738250

M3 - Journal article

C2 - 29082824

VL - 38

SP - 1418

EP - 1428

JO - Cephalalgia

JF - Cephalalgia

SN - 0800-1952

IS - 8

ER -