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Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

Editor-in-Chief: Breivik, Harald

4 Issues per year


CiteScore 2017: 0.84

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Volume 18, Issue 3

The effects of propranolol on heart rate variability and quantitative, mechanistic, pain profiling: a randomized placebo-controlled crossover study

Kristian Kjær Petersen
  • Corresponding author
  • SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
  • Center for Neuroplasticity and Pain (CNAP), SMI, Aalborg University, Aalborg, Denmark
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Hjalte Holm Andersen
  • SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Masato Tsukamoto
  • SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
  • Clinical Development Department, Asahi Kasei Pharma Corporation, Tokyo, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Lincoln Tracy
  • School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, VIC, Australia
  • School of Psychology, Faculty of Health Sciences, Australian Catholic University, VIC, Australia
  • Pain Management and Research Centre, Caulfield Hospital, VIC, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Julian Koenig
  • Section for Translational Psychobiology in Child and Adolescent Psychiatry, Department of Child and Adolescent Psychiatry, Centre for Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany
  • University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Lars Arendt-Nielsen
  • SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-06-02 | DOI: https://doi.org/10.1515/sjpain-2018-0054

Abstract

Background and aims

The autonomic nervous system (ANS) is capable of modulating pain. Aberrations in heart rate variability (HRV), reflective of ANS activity, are associated with experimental pain sensitivity, chronic pain, and more recently, pain modulatory mechanisms but the underlying mechanisms are still unclear. HRV is lowered during experimental pain as well as in chronic pain conditions and HRV can be increased by propranolol, which is a non-selective β-blocker. Sensitization of central pain pathways have been observed in several chronic pain conditions and human mechanistic pain biomarkers for these central pain pathways include temporal summation of pain (TSP) and conditioned pain modulation (CPM). The current study aimed to investigate the effect of the β-blocker propranolol, and subsequently assessing the response to standardized, quantitative, mechanistic pain biomarkers.

Methods

In this placebo-controlled, double-blinded, randomized crossover study, 25 healthy male volunteers (mean age 25.6 years) were randomized to receive 40 mg propranolol and 40 mg placebo. Heart rate, blood pressure, and HRV were assessed before and during experimental pain tests. Cuff pressure pain stimulation was used for assessment of pain detection (cPDTs) and pain tolerance (cPTTs) thresholds, TSP, and CPM. Offset analgesia (OA) was assessed using heat stimulation.

Results

Propranolol significantly reduced heart rate (p<0.001), blood pressure (p<0.02) and increased HRV (p<0.01) compared with placebo. No significant differences were found comparing cPDT (p>0.70), cPTT (p>0.93), TSP (p>0.70), OA-effect (p>0.87) or CPM (p>0.65) between propranolol and placebo.

Conclusions

The current study demonstrated that propranolol increased HRV, but did not affect pressure pain sensitivity or any pain facilitatory or modulatory outcomes.

Implications

Analgesic effects of propranolol have been reported in clinical pain populations and the results from the current study could indicate that increased HRV from propranolol is not associated with peripheral and central pain pathways in healthy male subjects.

Keywords: β-blockers; heart rate variability; conditioned pain modulation; offset analgesia; temporal summation of pain; pressure pain threshold

References

  • [1]

    Lebrec D, Nouel O, Corbic M, Benhamou JP. Propranolol – a medical treatment for portal hypertension? Lancet 1980;2:180–2.PubMedGoogle Scholar

  • [2]

    Steenen SA, van Wijk AJ, van der Heijden GJ, van Westrhenen R, de Lange J, de Jongh A. Propranolol for the treatment of anxiety disorders: systematic review and meta-analysis. J Psychopharmacol 2016;30:128–39.PubMedCrossrefGoogle Scholar

  • [3]

    Silberstein SD. Preventive migraine treatment. Neurol Clin 2009;27:429–43.CrossrefPubMedGoogle Scholar

  • [4]

    Tripathi D, Hayes PC. Beta-blockers in portal hypertension: new developments and controversies. Liver Int 2014;34:655–67.CrossrefPubMedGoogle Scholar

  • [5]

    Bendixen KH, Terkelsen AJ, Baad-Hansen L, Cairns BE, Svensson P. Effect of propranolol on hypertonic saline-evoked masseter muscle pain and autonomic response in healthy women during rest and mental arithmetic task. J Orofac Pain 2013;27:243–55.PubMedGoogle Scholar

  • [6]

    Thayer JF, Yamamoto SS, Brosschot JF. The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. Int J Cardiol 2010;141:122–31.CrossrefPubMedGoogle Scholar

  • [7]

    Thayer JF, Lane RD. The role of vagal function in the risk for cardiovascular disease and mortality. Biol Psychol 2007;74:224–42.CrossrefPubMedGoogle Scholar

  • [8]

    Thayer JF, Åhs F, Fredrikson M, Sollers JJ, Wager TD. A meta-analysis of heart rate variability and neuroimaging studies: Implications for heart rate variability as a marker of stress and health. Neurosci Biobehav Rev 2012;36:747–56.CrossrefPubMedGoogle Scholar

  • [9]

    Koenig J, Jarczok MN, Ellis RJ, Hillecke TK, Thayer JF. Heart rate variability and experimentally induced pain in healthy adults: a systematic review. Eur J Pain 2013;18:1–14.Google Scholar

  • [10]

    Thayer JF, Sternberg EM. Neural concomitants of immunity – focus on the vagus nerve. Neuroimage 2009;47:908–10.PubMedCrossrefGoogle Scholar

  • [11]

    Ballegaard S, Bergmann N, Karpatschof B, Kristiansen J, Gyntelberg F, Arendt-Nielsen L, Bech P, Hjalmarson Å, Faber J. Association between pressure pain sensitivity and autonomic function as assessed by a tilt table test. Scand J Clin Lab Invest 2015;75:345–54.CrossrefPubMedGoogle Scholar

  • [12]

    Tracy LM, Ioannou L, Baker KS, Gibson SJ, Georgiou-Karistianis N, Giummarra MJ. Meta-analytic evidence for decreased heart rate variability in chronic pain implicating parasympathetic nervous system dysregulation. Pain 2016;157:7–29.PubMedCrossrefGoogle Scholar

  • [13]

    Lerma C, Martinez A, Ruiz N, Vargas A, Infante O, Martinez-Lavin M. Nocturnal heart rate variability parameters as potential fibromyalgia biomarker: correlation with symptoms severity. Arthritis Res Ther 2011;13:R185.CrossrefPubMedGoogle Scholar

  • [14]

    Bossmann T, Brauner T, Wearing S, Horstmann T. Predictors of chronic pain following total knee replacement in females and males: an exploratory study. Pain Manag 2017;7:391–403.CrossrefPubMedGoogle Scholar

  • [15]

    Light KC, Bragdon EE, Grewen KM, Brownley KA, Girdler SS, Maixner W. Adrenergic dysregulation and pain with and without acute beta-blockade in women with fibromyalgia and temporomandibular disorder. J Pain 2009;10:542–52.CrossrefPubMedGoogle Scholar

  • [16]

    Tchivileva IE, Lim PF, Smith SB, Slade GD, Diatchenko L, McLean SA, Maixner W. Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study. Pharmacogenet Genomics 2010;20:239–48.PubMedGoogle Scholar

  • [17]

    Chu LF, Cun T, Ngai LK, Kim JE, Zamora AK, Young CA, Angst MS, Clark DJ. Modulation of remifentanil-induced postinfusion hyperalgesia by the β-blocker propranolol in humans. Pain 2012;153:974–81.CrossrefPubMedGoogle Scholar

  • [18]

    Hartung JE, Ciszek BP, Nackley AG. β2- and β3-adrenergic receptors drive COMT-dependent pain by increasing production of nitric oxide and cytokines. Pain 2014;155:1346–55.PubMedCrossrefGoogle Scholar

  • [19]

    Kline RH, Exposto FG, O’Buckley SC, Westlund KN, Nackley AG. Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat. Neuroscience 2015;290: 561–9.CrossrefPubMedGoogle Scholar

  • [20]

    Nackley AG, Tan KS, Fecho K, Flood P, Diatchenko L, Maixner W. Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both β2- and β3-adrenergic receptors. Pain 2007;128:199–208.CrossrefPubMedGoogle Scholar

  • [21]

    Ernberg M, Lundeberg T, Kopp S. Pain and allodynia/hyperalgesia induced by intramuscular injection of serotonin in patients with fibromyalgia and healthy individuals. Pain 2000;85:31–9.PubMedCrossrefGoogle Scholar

  • [22]

    Ernberg M, Lundeberg T, Kopp S. Effect of propranolol and granisetron on experimentally induced pain and allodynia/hyperalgesia by intramuscular injection of serotonin into the human masseter muscle. Pain 2000;84:339–46.PubMedCrossrefGoogle Scholar

  • [23]

    Khasar SG, McCarter G, Levine JD. Epinephrine produces a beta-adrenergic receptor-mediated mechanical hyperalgesia and in vitro sensitization of rat nociceptors. J Neurophysiol 1999;81:1104–12.PubMedCrossrefGoogle Scholar

  • [24]

    Yalcin I, Choucair-Jaafar N, Benbouzid M, Tessier LH, Muller A, Hein L, Freund-Mercier MJ, Barrot M. β2-Adrenoceptors are critical for antidepressant treatment of neuropathic pain. Ann Neurol 2009;65:218–25.CrossrefGoogle Scholar

  • [25]

    Yarnitsky D. Role of endogenous pain modulation in chronic pain mechanisms and treatment. Pain 2015;156 Suppl:S24–31.Google Scholar

  • [26]

    Arendt-Nielsen L, Skou ST, Nielsen TA, Petersen KK. Altered central sensitization and pain modulation in the CNS in chronic joint pain. Curr Osteoporos Rep 2015;13:225–34.PubMedCrossrefGoogle Scholar

  • [27]

    Graven-Nielsen T, Arendt-Nielsen L. Assessment of mechanisms in localized and widespread musculoskeletal pain. Nat Rev Rheumatol 2010;6:599–606.CrossrefPubMedGoogle Scholar

  • [28]

    Olesen SS, Brock C, Krarup AL, Funch-Jensen P, Arendt-Nielsen L, Wilder-Smith OH, Drewes AM. Descending inhibitory pain modulation is impaired in patients with chronic pancreatitis. Clin Gastroenterol Hepatol 2010;8:724–30.PubMedCrossrefGoogle Scholar

  • [29]

    Hermans L, Calders P, Van Oosterwijck J, Verschelde E, Bertel E, Meeus M. An overview of offset analgesia and the comparison with conditioned pain modulation: a systematic literature review. Pain Physician 2016;19:307–26.PubMedGoogle Scholar

  • [30]

    Grill JD, Coghill RC. Transient analgesia evoked by noxious stimulus offset. J Neurophysiol 2002;87:2205–8.PubMedCrossrefGoogle Scholar

  • [31]

    Honigman L, Yarnitsky D, Sprecher E, Weissman-Fogel I. Psychophysical testing of spatial and temporal dimensions of endogenous analgesia: conditioned pain modulation and offset analgesia. Exp Brain Res 2013;228:493–501.PubMedCrossrefGoogle Scholar

  • [32]

    Niesters M, Dahan A, Swartjes M, Noppers I, Fillingim RB, Aarts L, Sarton EY. Effect of ketamine on endogenous pain modulation in healthy volunteers. Pain 2011;152:656–63.PubMedCrossrefGoogle Scholar

  • [33]

    Niesters M, Hoitsma E, Sarton E, Aarts L, Dahan A. Offset analgesia in neuropathic pain patients and effect of treatment with morphine and ketamine. Anesthesiology 2011;115:1063–71.PubMedCrossrefGoogle Scholar

  • [34]

    Niesters M, Proto PL, Aarts L, Sarton EY, Drewes AM, Dahan A. Tapentadol potentiates descending pain inhibition in chronic pain patients with diabetic polyneuropathy. Br J Anaesth 2014;113:148–56.CrossrefPubMedGoogle Scholar

  • [35]

    Weissman-Fogel I, Granovsky Y, Crispel Y, Ben-Nun A, Best LA, Yarnitsky D, Granot M. Enhanced presurgical pain temporal summation response predicts post-thoracotomy pain intensity during the acute postoperative phase. J Pain 2009;10:628–36.CrossrefPubMedGoogle Scholar

  • [36]

    Petersen KK, Arendt-Nielsen L, Simonsen O, Wilder-Smith O, Laursen MB. Presurgical assessment of temporal summation of pain predicts the development of chronic postoperative pain 12 months after total knee replacement. Pain 2015;156:55–61.PubMedCrossrefGoogle Scholar

  • [37]

    Petersen KK, Simonsen O, Laursen MB, Arendt-Nielsen L. The role of preoperative radiologic severity, sensory testing, and temporal summation on chronic postoperative pain following total knee arthroplasty. Clin J Pain 2018;34:193–7.PubMedGoogle Scholar

  • [38]

    Thuillez C, Richer C, Duhazé P, Bergougnan L, Giudicelli JF. Beta-adrenoceptor blocking effects and plasma levels of bornaprolol and propranolol in man. Eur J Clin Pharmacol 1985;29:405–11.CrossrefPubMedGoogle Scholar

  • [39]

    Izumi M, Petersen KK, Laursen MB, Arendt-Nielsen L, Graven-Nielsen T. Facilitated temporal summation of pain correlates with clinical pain intensity after hip arthroplasty. Pain 2017;158:323–32.CrossrefPubMedGoogle Scholar

  • [40]

    Gamelin FX, Berthoin S, Bosquet L. Validity of the polar S810 heart rate monitor to measure R-R intervals at rest. Med Sci Sports Exerc 2006;38:887–93.CrossrefGoogle Scholar

  • [41]

    Andersen HH, Imai Y, Petersen KK, Koenig J, Elberling J, Arendt-Nielsen L. Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers. Somatosens Mot Res 2016;33:49–60.CrossrefPubMedGoogle Scholar

  • [42]

    Nahman-Averbuch H, Dayan L, Sprecher E, Hochberg U, Brill S, Yarnitsky D, Jacob G. Sex differences in the relationships between parasympathetic activity and pain modulation. Physiol Behav 2016;154:40–8.PubMedCrossrefGoogle Scholar

  • [43]

    Nahman-Averbuch H, Dayan L, Sprecher E, Hochberg U, Brill S, Yarnitsky D, Jacob G. Pain modulation and autonomic function: the effect of clonidine. Pain Med 2016;17:1292–301.CrossrefGoogle Scholar

  • [44]

    Graven-Nielsen T, Vaegter HB, Finocchietti S, Handberg G, Arendt-Nielsen L. Assessment of musculoskeletal pain sensitivity and temporal summation by cuff pressure algometry. Pain 2015;156:2193–202.CrossrefPubMedGoogle Scholar

  • [45]

    Manafi Khanian B, Arendt-Nielsen L, Kjær Petersen K, Samani A, Graven-Nielsen T. Interface pressure behavior during painful cuff algometry. Pain Med 2016;17:915–23.PubMedGoogle Scholar

  • [46]

    Petersen KK, Graven-Nielsen T, Simonsen O, Laursen MB, Arendt-Nielsen L. Preoperative pain mechanisms assessed by cuff algometry are associated with chronic postoperative pain relief after total knee replacement. Pain 2016;157:1400–6.PubMedCrossrefGoogle Scholar

  • [47]

    Vaegter HB, Graven-Nielsen T. Pain modulatory phenotypes differentiate subgroups with different clinical and experimental pain sensitivity. Pain 2016;157:1480–8.CrossrefPubMedGoogle Scholar

  • [48]

    Petersen KK, Arendt-Nielsen L, Finocchietti S, Hirata RP, Simonsen O, Laursen MB, Graven-Nielsen T. Age interactions on pain sensitization in patients with severe knee osteoarthritis and controls. Clin J Pain 2017;33:1081–7.PubMedGoogle Scholar

  • [49]

    Ligato D, Petersen KK, Mørch CD, Arendt-Nielsen L. Offset analgesia: the role of peripheral and central mechanisms. Eur J Pain 2018;22:142–9.PubMedCrossrefGoogle Scholar

  • [50]

    Imai Y, Petersen KK, Mørch CD, Arendt Nielsen L. Comparing test–retest reliability and magnitude of conditioned pain modulation using different combinations of test and conditioning stimuli. Somatosens Mot Res 2016;33:169–77.CrossrefPubMedGoogle Scholar

  • [51]

    Biurrun Manresa JA, Fritsche R, Vuilleumier PH, Oehler C, Mørch CD, Arendt-Nielsen L, Andersen OK, Curatolo M. Is the conditioned pain modulation paradigm reliable? A test-retest assessment using the nociceptive withdrawal reflex. PLoS One 2014;9:e100241.PubMedCrossrefGoogle Scholar

  • [52]

    Vaegter HB, Handberg G, Graven-Nielsen T. Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans. Pain 2014;155:158–67.CrossrefPubMedGoogle Scholar

  • [53]

    Khasar SG, Green PG, Miao FJP, Levine JD. Vagal modulation of nociception is mediated by adrenomedullary epinephrine in the rat. Eur J Neurosci 2003;17:909–15.CrossrefPubMedGoogle Scholar

  • [54]

    Khasar SG, Miao FJP, Jänig W, Levine JD. Modulation of bradykinin-induced mechanical hyperalgesia in the rat by activity in abdominal vagal afferents. Eur J Neurosci 1998;10:435–44.PubMedCrossrefGoogle Scholar

  • [55]

    Ren K, Zhuo M, Randich A, Gebhart GF. Vagal afferent stimulation-produced effects on nociception in capsaicin-treated rats. J Neurophysiol 1993;69:1530–40.PubMedCrossrefGoogle Scholar

  • [56]

    Busch V, Zeman F, Heckel A, Menne F, Ellrich J, Eichhammer P. The effect of transcutaneous vagus nerve stimulation on pain perception – an experimental study. Brain Stimul 2013;6: 202–9.CrossrefPubMedGoogle Scholar

  • [57]

    Sedan O, Sprecher E, Yarnitsky D. Vagal stomach afferents inhibit somatic pain perception. Pain 2005;113:354–9.PubMedCrossrefGoogle Scholar

  • [58]

    Ghione S. Hypertension-associated hypalgesia: evidence in experimental animals and humans, pathophysiological mechanisms, and potential clinical consequences. Hypertension 1996;28:494–504.CrossrefPubMedGoogle Scholar

  • [59]

    Thurston CL, Randich A. Effects of vagal afferent stimulation on ON and OFF cells in the rostroventral medulla: relationships to nociception and arterial blood pressure. J Neurophysiol 1992;67:180–96.PubMedCrossrefGoogle Scholar

  • [60]

    Appelhans BM, Luecken LJ. Heart rate variability and pain: associations of two interrelated homeostatic processes. Biol Psychol 2008;77:174–82.CrossrefPubMedGoogle Scholar

  • [61]

    Duschek S, Mück I, Reyes del Paso GA. Relationship between baroreceptor cardiac reflex sensitivity and pain experience in normotensive individuals. Int J Psychophysiol 2007;65:193–200.PubMedCrossrefGoogle Scholar

  • [62]

    Reyes del Paso GA, Garrido S, Pulgar Á, Duschek S. Autonomic cardiovascular control and responses to experimental pain stimulation in fibromyalgia syndrome. J Psychosom Res 2011;70:125–34.PubMedCrossrefGoogle Scholar

  • [63]

    Nahman-Averbuch H, Granovsky Y, Sprecher E, Steiner M, Tzuk-Shina T, Pud D, Yarnitsky D. Associations between autonomic dysfunction and pain in chemotherapy-induced polyneuropathy. Eur J Pain 2014;18:47–55.PubMedCrossrefGoogle Scholar

  • [64]

    Boyer N, Signoret-Genest J, Artola A, Dallel R, Monconduit L. Propranolol treatment prevents chronic central sensitization induced by repeated dural stimulation. Pain 2017;158: 2025–34.CrossrefPubMedGoogle Scholar

  • [65]

    Singh JP, Kandala J, John Camm A. Non-pharmacological modulation of the autonomic tone to treat heart failure. Eur Heart J 2014;35:77–85.CrossrefPubMedGoogle Scholar

  • [66]

    Napadow V, Edwards RR, Cahalan CM, Mensing G, Greenbaum S, Valovska A, Li A, Kim J, Maeda Y, Park K, Wasan AD. Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation. Pain Med 2012;13:777–89.CrossrefPubMedGoogle Scholar

  • [67]

    Pedretti R, Colombo E, Braga SS, Carú B. Influence of transdermal scopolamine on cardiac sympathovagal interaction after acute myocardial infarction. Am J Cardiol 1993;72:384–92.CrossrefPubMedGoogle Scholar

  • [68]

    La Rovere MT, Mortara A, Pantaleo P, Maestri R, Cobelli F, Tavazzi L. Scopolamine improves autonomic balance in advanced congestive heart failure. Circulation 1994;90: 838–43.PubMedCrossrefGoogle Scholar

  • [69]

    Perlstein I, Stepensky D, Krzyzanski W, Hoffman A. A signal transduction pharmacodynamic model of the kinetics of the parasympathomimetic activity of low-dose scopolamine and atropine in rats. J Pharm Sci 2002;91:2500–10.CrossrefPubMedGoogle Scholar

  • [70]

    Ali-Melkkilä T, Kaila T, Antila K, Halkola L, Iisalo E. Effects of glycopyrrolate and atropine on heart rate variability. Acta Anaesthesiol Scand 1991;35:436–41.PubMedCrossrefGoogle Scholar

  • [71]

    Shields JW. Heart rate variability with deep breathing as a clinical test of cardiovagal function. Cleve Clin J Med 2009;76(Suppl. 2):37–40.CrossrefGoogle Scholar

  • [72]

    Bartley EJ, Fillingim RB. Sex differences in pain: A brief review of clinical and experimental findings. Br J Anaesth 2013;111: 52–8.CrossrefGoogle Scholar

  • [73]

    Greenspan JD, Craft RM, Greenspan JD, Craft RM, LeResche L, Arendt-Nielsen L, Berkley KJ, Fillingim RB, Gold MS, Holdcroft A, Lautenbacher S, Mayer EA, Mogil JS, Murphy AZ, Traub RJ. Studying sex and gender differences in pain and analgesia: a consensus report. Pain 2007;132(Suppl):S26–45.PubMedCrossrefGoogle Scholar

  • [74]

    Quartana PJ, Campbell CM, Edwards RR. Pain catastrophizing: a critical review. Expert Rev Neurother 2009;9:745–58.PubMedCrossrefGoogle Scholar

  • [75]

    Graven-Nielsen T, Izumi M, Petersen KK, Arendt-Nielsen L. User-independent assessment of conditioning pain modulation by cuff pressure algometry. Eur J Pain 2017;21:552–61.CrossrefPubMedGoogle Scholar

  • [76]

    Ladda J, Straube A, Förderreuther S, Krause P, Eggert T. Quantitative sensory testing in cluster headache: increased sensory thresholds. Cephalalgia 2006;26:1043–50.CrossrefPubMedGoogle Scholar

  • [77]

    Yarnitsky D, Arendt-Nielsen L, Bouhassira D, Edwards RR, Fillingim RB, Granot M, Hansson P, Lautenbacher S, Marchand S, Wilder-Smith OH. Recommendations on terminology and practice of psychophysical DNIC testing. Eur J Pain 2010;14:339.PubMedCrossrefGoogle Scholar

  • [78]

    Nahman-Averbuch H, Martucci KT, Granovsky Y, Weissman-Fogel I, Yarnitsky D, Coghill RC. Distinct brain mechanisms support spatial vs temporal filtering of nociceptive information. Pain 2014;155:2491–501.PubMedCrossrefGoogle Scholar

  • [79]

    Van Den Houte M, Van Oudenhove L, Bogaerts K, Van Diest I, Van den Bergh O. Endogenous pain modulation: association with resting heart rate variability and negative affectivity. Pain Med 2017:1–10. [Epub ahead of print].Google Scholar

  • [80]

    Bouhassira D, Bing Z, Le Bars D. Effects of lesions of locus coeruleus/subcoeruleus on diffuse noxious inhibitory controls in the rat. Brain Res 1992;571:140–4.PubMedCrossrefGoogle Scholar

  • [81]

    Schweinhardt P, Abulhasan YB, Koeva V, Balderi T, Kim DJ, Alhujairi M, Carli F. Effects of intravenous propranolol on heat pain sensitivity in healthy men. Eur J Pain 2013;17:704–13.PubMedCrossrefGoogle Scholar

  • [82]

    Maekawa K, Kuboki T, Miyawaki T, Shimada M, Yamashita A, Clark GT. Effect of intravenous infusion of a beta-adrenergic blocking agent on the haemodynamic changes in human masseter muscle induced by cold-pressor stimulation. Arch Oral Biol 1999;44:475–83.PubMedCrossrefGoogle Scholar

  • [83]

    Butt JH, Dalsgaard S, Torp-Pedersen C, Køber L, Gislason GH, Kruuse C, Fosbøl EL. Beta-blockers for exams identify students at high risk of psychiatric morbidity. J Child Adolesc Psychopharmacol 2016;27:266–73.PubMedGoogle Scholar

  • [84]

    Safieh-Garabedian B, Poole S, Haddad JJ, Massaad CA, Jabbur SJ, Saadé NE. The role of the sympathetic efferents in endotoxin-induced localized inflammatory hyperalgesia and cytokine upregulation. Neuropharmacology 2002;42:864–72.CrossrefPubMedGoogle Scholar

  • [85]

    Andersen HH, Elberling J, Sharma N, Hauberg LE, Gazerani P, Arendt-Nielsen L. Histaminergic and non-histaminergic elicited itch is attenuated in capsaicin-evoked areas of allodynia and hyperalgesia: a healthy volunteer study. Eur J Pain 2017;21:1098–109.PubMedCrossrefGoogle Scholar

  • [86]

    Andersen HH, Gazerani P, Arendt-Nielsen L. High-concentration L-menthol exhibits counter-irritancy to neurogenic inflammation, thermal and mechanical hyperalgesia caused by trans-cinnamaldehyde. J Pain 2016;17:919–29.CrossrefPubMedGoogle Scholar

About the article

Corresponding author: Kristian Kjær Petersen, Associate Professor, PhD, SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Fredrik Bajers Vej 7 D3, DK-9220 Aalborg, Denmark, Phone: +45 9940 7529, Fax: +45 9815 4008


Received: 2018-03-12

Revised: 2018-04-13

Accepted: 2018-04-23

Published Online: 2018-06-02

Published in Print: 2018-07-26


Authors’ statements

Research funding: The authors thank The Innovation Fund Denmark (j.no. 136-2014-5), The Shionogi Science Program and the TaNeDS Europe grant for providing the opportunity to conduct the study.

Conflict of interest: Masato Tsukamoto is an employee of Asahi Kasei Pharma Corporation.

Informed consent: All participants were given oral and written information and signed written informed consent prior to the initiation of the study.

Ethical approval: The study complied with the Helsinki Declaration, was approved by the local Ethical Committee (reference number: N-20120043), and registered at ClinicalTrials.gov (registration number: NCT02808611).


Citation Information: Scandinavian Journal of Pain, Volume 18, Issue 3, Pages 479–489, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1515/sjpain-2018-0054.

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