Acute physiological and electrical accentuation of vagal tone has no effect on pain or gastrointestinal motility in chronic pancreatitis

Figures & data

Figure 1 Study protocol.

Abbreviations: t-VNS, noninvasive transcutaneous electrical vagal nerve stimulation; DSB, deep slow breathing; SB, sham breathing.

Figure 2 Experimental procedures.

Abbreviations: QST, quantitative sensory testing; CPM, conditioned pain modulation; t-VNS, noninvasive transcutaneous electrical vagal nerve stimulation; DSB, deep slow breathing; SB, sham breathing.

Table 1 Demographic and clinical characteristics of patients

Variables	Values
Male, n (%)	12 (60)
Mean age in years (range)	60.7 (50–78)
Duration of CP in months (range)	92.4 (9–249)
Painful CP (duration of pain >12 weeks), n (%)	14 (70)
Non-painful CP, n (%)	6 (30)
Etiology, n (%)
Toxic/metabolic	11 (55)
Idiopathic	3 (15)
Genetic	0 (0)
Autoimmune	1 (5)
Recurrent	1 (5)
Obstructive	4 (20)
BMI (kg/m^2)	23.7 (18.8–36.9)
Diabetes mellitus, n (%)
NIDDM	3 (15)
IDDM	6 (30)
Ongoing alcohol abuse, n (%)	0 (0)
Current smoker, n (%)	13 (65)
Analgesics, n (%)
NSAIDs/paracetamol	14 (70)
Tramadol/codeine	8 (40)
Opioids	7 (35)
Adjuvants (tricyclic antidepressants, gabapentin, pregabalin)	3 (15)
Opioid equivalents in mg (range)	33.0 (0–120)
Rescue medication, n (%)
Strong opioids	9 (45)
Weak opioids and/or paracetamol	5 (25)
Complications to CP, n (%)	11 (55)
EPI
Pseudocysts	4 (20)
Bile duct obstruction	2 (10)
Duodenal stenosis	0 (0)
Splenic vein thrombosis	0 (0)

Abbreviations: CP, chronic pancreatitis; BMI, body mass index; NIDDM, non-insulin-dependent diabetes mellitus; IDDM, insulin-dependent diabetes mellitus; NSAIDs, non-steroid anti-inflammatory drugs; EPI, exocrine pancreatic insufficiency.

Figure 3 Changes in cardiac-derived parameters boxplot.

Notes: Median and upper and lower quantiles shown. Whiskers represent minimum and maximum. Dots represent outliers.

Table 2 Cardiac-derived parameters and QST in CP patients before and after vagal tone modulation (deep breathing combined with t-VNS) and sham stimulation

Test modality	Parameter (unit)	Baseline	Vagal tone modulation	Baseline	Sham modulation	P-valuea
Cardiac-derived parameters	Heart rate (beats/min)	74.6±12.3	74.7±10.7	72.5±11.8	69.7±10.1***	0.0004
	Cardiac vagal tone (linear vagal scale)	3.6±2.2	6.2±4.8**	4.1±2.3	3.9±2.3	0.02
	Diastolic blood pressure (mmHg)	70.2±14.3	64.0±19.6	68.3±13.9	67.3±14.0	0.36
	Systolic blood pressure (mmHg)	118.8±21.1	114.7±20.7	111.7±20.8	120.6±23.4**	0.18
	Mean blood pressure (mmHg)	86.4±15.5	81.6±16.0*	82.7±15.7	85.1±15.5	0.21
Quantitative sensory testing	Muscle pressure pain threshold (kPa)	939±237	991±342	972±81	989±336	0.97
	Bone pressure pain threshold (kPa)	155±57	170±88	989±336	161±63	0.67
	Cold pressor test (seconds)	–	80±47	–	85±46	0.14
	CPM (%)	–	7.6±22.5	–	26.6±18.8	0.02

Notes: Data presented as mean ± SD.

a Vagal tone modulation vs. sham modulation (between-group analysis). Significance of the difference between baseline and vagal tone/sham modulation (within-group analysis);

* P<0.05;

** P<0.01;

*** P<0.001.

Abbreviations: QST, quantitative sensory testing; CP, chronic pancreatitis; VNS, vagal nerve stimulation; CPM, conditioned pain modulation.

Figure 4 Changes in pain pressure thresholds.

Abbreviations: PPT, pressure pain threshold; CP, cold pressor test of 120 seconds.