A double-blind, placebo-controlled study of repetitive transnasal sphenopalatine ganglion blockade with tx360(®) as acute treatment for chronic migraine

Abstract

Objective: To determine if repetitive sphenopalatine ganglion (SPG) blocks with 0.5% bupivacaine delivered through the Tx360(®) are superior in reducing pain associated with chronic migraine (CM) compared with saline.

Background: The SPG is a small concentrated structure of neuronal tissue that resides within the pterygopalatine fossa (PPF) in close proximity to the sphenopalatine foramen and is innervated by the maxillary division of the trigeminal nerve. From an anatomical and physiological perspective, SPG blockade may be an effective acute and preventative treatment for CM.

Method: This was a double-blind, parallel-arm, placebo-controlled, randomized pilot study using a novel intervention for acute treatment in CM. Up to 41 subjects could be enrolled at 2 headache specialty clinics in the US. Eligible subjects were between 18 and 80 years of age and had a history of CM defined by the second edition of the International Classification of Headache Disorders appendix definition. They were allowed a stable dose of migraine preventive medications that was maintained throughout the study. Following a 28-day baseline period, subjects were randomized by computer-generated lists of 2:1 to receive 0.5% bupivacaine or saline, respectively. The primary end-point was to compare numeric rating scale scores at pretreatment baseline vs 15 minutes, 30 minutes, and 24 hours postprocedure for all 12 treatments. SPG blockade was accomplished with the Tx360(®) , which allows a small flexible soft plastic tube that is advanced below the middle turbinate just past the pterygopalatine fossa into the intranasal space. A 0.3 cc of anesthetic or saline was injected into the mucosa covering the SPG. The procedure is performed similarly in each nostril. The active phase of the study consisted of a series of 12 SPG blocks with 0.3 cc of 0.5% bupivacaine or saline provided 2 times per week for 6 weeks. Subjects were re-evaluated at 1 and 6 months postfinal procedure.

Results: The final dataset included 38 subjects, 26 in the bupivacaine group and 12 in the saline group. A repeated measures analysis of variance showed that subjects receiving treatment with bupivacaine experienced a significant reduction in the numeric rating scale scores compared with those receiving saline at baseline (M=3.78 vs M=3.18, P=.10), 15 minutes (M=3.51 vs M=2.53, P<.001), 30 minutes (M=3.45 vs M=2.41, P<.001), and 24 hours after treatment (M=4.20 vs M=2.85, P<.001), respectively. Headache Impact Test-6 scores were statistically significantly decreased in subjects receiving treatments with bupivacaine from before treatment to the final treatment (Mdiff = -4.52, P=.005), whereas no significant change was seen in the saline group (Mdiff = -1.50, P=.13).

Conclusion: SPG blockade with bupivacaine delivered repetitively for 6 weeks with the Tx360(®) device demonstrates promise as an acute treatment of headache in some subjects with CM. Statistically significant headache relief is noted at 15 and 30 minutes and sustained at 24 hours for SPG blockade with bupivacaine vs saline. The Tx360(®) device was simple to use and not associated with any significant or lasting adverse events. Further research on sphenopalatine ganglion blockade is warranted.

Trial registration: ClinicalTrials.gov NCT01709708.

Keywords: Tx360®; acute treatment; chronic migraine; preventive treatment; sphenopalatine ganglion block.

© 2014 The Authors. Headache published by Wiley Periodicals, Inc. on behalf of American Headache Society.

Figures

Fig 1

Sphenopalatine ganglion. Reproduced with permission from Primary Care Network©.

Fig 2

Study flow diagram.

Fig 3

Treatment with bupivacaine delivered with the Tx360® device reduced average pooled numeric rating scale (NRS) scores compared with those treated with saline. Average NRS scores from all treatments pooled are shown. Between group P values: Before treatment *P = .010; 15 minutes, 30 minutes, and 24 hours posttreatment **P < .001.

Fig 4

Average numeric rating scale scores 15 minutes after repetitive sphenopalatine blocks with either bupivacaine or sham saline.

Fig 5

Average numeric rating scale scores 30 minutes after repetitive sphenopalatine blocks with either bupivacaine or saline.

Fig 6

Average numeric rating scale scores 24 hours after repetitive sphenopalatine blocks with either bupivacaine or saline.

Fig 7

Subjects treated with bupivacaine had a statistically significant greater decrease in pooled numeric rating scale scores from baseline compared to those receiving sham saline. Between group P values: 15 minutes, 30 minutes, 24 hours posttreatment P < .001.

Fig 8

Repetitive sphenopalatine blocks with bupivacaine caused a statistically significant decrease in Headache Impact Test-6 scores, P = .005*; bupivacaine n = 25, saline n = 11.