Is the Volume of the Caudate Nuclei Associated With Area of Secondary Hyperalgesia? - Protocol for a 3-Tesla MRI Study of Healthy Volunteers

Morten Sejer Hansen, Mohammad Sohail Asghar, Jørn Wetterslev, Christian Bressen Pipper, Johan Johan Mårtensson, Lino Becerra, Anders Christensen, Janus Damm Nybing, Inger Havsteen, Mikael Boesen, Jørgen Berg Dahl, Morten Sejer Hansen, Mohammad Sohail Asghar, Jørn Wetterslev, Christian Bressen Pipper, Johan Johan Mårtensson, Lino Becerra, Anders Christensen, Janus Damm Nybing, Inger Havsteen, Mikael Boesen, Jørgen Berg Dahl

Abstract

Background: Experience and development of pain may be influenced by a number of physiological, psychological, and psychosocial factors. In a previous study we found differences in neuronal activation to noxious stimulation, and microstructural neuroanatomical differences, when comparing healthy volunteers with differences in size of the area of secondary hyperalgesia following a standardized burn injury.

Objective: We aim to investigate the degree of association between the volume of pain-relevant structures in the brain and the size of the area of secondary hyperalgesia following brief thermal sensitization.

Methods: The study consists of one experimental day, in which whole-brain magnetic resonance imaging (MRI) scans will be conducted including T1-weighed three-dimensional anatomy scan, diffusion tensor imaging, and resting state functional MRI. Before the experimental day, all included participants will undergo experimental pain testing in a parallel study (Clinicaltrials.gov Identifier: NCT02527395). Results from this experimental pain testing, as well as the size of the area of secondary hyperalgesia from the included participants, will be extracted from this parallel study.

Results: The association between the volume of pain-relevant structures in the brain and the area of secondary hyperalgesia will be investigated by linear regression of the estimated best linear unbiased predictors on the individual volumes of the pain relevant brain structures.

Conclusions: We plan to investigate the association between experimental pain testing parameters and the volume, connectivity, and resting state activity of pain-relevant structures in the brain. These results may improve our knowledge of the mechanisms responsible for the development of acute and chronic pain.

Clinicaltrial: Danish Research Ethics Committee (identifier: H-15010473). Danish Data Protection Agency (identifier: RH-2015-149). Clinicaltrials.gov NCT02567318; https://ichgcp.net/clinical-trials-registry/NCT02567318 (Archived by WebCite at http://www.webcitation.org/6i4OtP0Oi).

Keywords: Anaesthesiology; Central sensitization; Hyperalgesia; Magnetic resonance imaging; Pain; Physiology; Quantitative sensory testing.

Conflict of interest statement

Conflicts of Interest: None declared.

Figures

Figure 1
Figure 1
Schematic presentation of experimental day. Abbreviations: MRI, Magnetic Resonance Imaging; fMRI, Functional Magnetic Resonance Imaging.

References

    1. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009 Sep;10(9):895–926. doi: 10.1016/j.jpain.2009.06.012.
    1. Naert AL, Kehlet H, Kupers R. Characterization of a novel model of tonic heat pain stimulation in healthy volunteers. Pain. 2008 Aug 15;138(1):163–71. doi: 10.1016/j.pain.2007.11.018.
    1. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011 Mar;152(3 Suppl):S2–15. doi: 10.1016/j.pain.2010.09.030.
    1. Ziegler EA, Magerl W, Meyer RA, Treede RD. Secondary hyperalgesia to punctate mechanical stimuli. Central sensitization to A-fibre nociceptor input. Brain. 1999 Dec;122 ( Pt 12):2245–57.
    1. Treede R. Chapter 1 pain and hyperalgesia: definitions and theories. Handb Clin Neurol. 2006;81:3–10. doi: 10.1016/S0072-9752(06)80005-9.
    1. Petersen KL, Rowbotham MC. A new human experimental pain model: the heat/capsaicin sensitization model. Neuroreport. 1999 May 14;10(7):1511–6.
    1. Staahl C, Olesen A, Andresen T, Arendt-Nielsen L, Drewes A. Assessing efficacy of non-opioid analgesics in experimental pain models in healthy volunteers: an updated review. Br J Clin Pharmacol. 2009 Sep;68(3):322–41. doi: 10.1111/j.1365-2125.2009.03433.x.
    1. Dirks J, Petersen K, Dahl J. The heat/capsaicin sensitization model: a methodologic study. J Pain. 2003 Apr;4(3):122–8.
    1. Mathiesen O, Imbimbo BP, Hilsted KL, Fabbri L, Dahl JB. CHF3381, a N-methyl-D-aspartate receptor antagonist and monoamine oxidase-A inhibitor, attenuates secondary hyperalgesia in a human pain model. J Pain. 2006 Aug;7(8):565–74. doi: 10.1016/j.jpain.2006.02.004.
    1. Werner MU, Petersen KL, Rowbotham MC, Dahl JB. Healthy volunteers can be phenotyped using cutaneous sensitization pain models. PLoS One. 2013 May;8(5):e62733. doi: 10.1371/journal.pone.0062733.
    1. Asghar MS, Pereira MP, Werner MU, Mårtensson J, Larsson HB, Dahl JB. Secondary hyperalgesia phenotypes exhibit differences in brain activation during noxious stimulation. PLoS One. 2015;10(1):e0114840. doi: 10.1371/journal.pone.0114840.
    1. Borsook D, Upadhyay J, Chudler EH, Becerra L. A key role of the basal ganglia in pain and analgesia--insights gained through human functional imaging. Mol Pain. 2010;6:27. doi: 10.1186/1744-8069-6-27.
    1. Barker RA. The basal ganglia and pain. Int J Neurosci. 1988 Jul;41(1-2):29–34.
    1. Chudler EH, Dong WK. The role of the basal ganglia in nociception and pain. Pain. 1995 Jan;60(1):3–38.
    1. Absinta M, Rocca MA, Colombo B, Falini A, Comi G, Filippi M. Selective decreased grey matter volume of the pain-matrix network in cluster headache. Cephalalgia. 2012 Jan;32(2):109–15. doi: 10.1177/0333102411431334.
    1. de Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Werf SP, van der Meer JW, Toni I. Neural correlates of the chronic fatigue syndrome--an fMRI study. Brain. 2004 Sep;127(Pt 9):1948–57. doi: 10.1093/brain/awh225.
    1. Freund W, Klug R, Weber F, Stuber G, Schmitz B, Wunderlich AP. Perception and suppression of thermally induced pain: a fMRI study. Somatosens Mot Res. 2009 Mar;26(1):1–10. doi: 10.1080/08990220902738243.
    1. Freund W, Stuber G, Wunderlich AP, Schmitz B. Cortical correlates of perception and suppression of electrically induced pain. Somatosens Mot Res. 2007 Dec;24(4):203–12. doi: 10.1080/08990220701723636.
    1. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 2002 May;46(5):1333–43. doi: 10.1002/art.10225.
    1. Li M, Yan J, Li S, Wang T, Zhan W, Wen H, Ma X, Zhang Y, Tian J, Jiang G. Reduced volume of gray matter in patients with trigeminal neuralgia. Brain Imaging Behav. 2016 Feb 22; doi: 10.1007/s11682-016-9529-2.
    1. Luchtmann M, Steinecke Y, Baecke S, Lützkendorf R, Bernarding J, Kohl J, Jöllenbeck B, Tempelmann C, Ragert P, Firsching R. Structural brain alterations in patients with lumbar disc herniation: a preliminary study. PLoS One. 2014;9(3):e90816. doi: 10.1371/journal.pone.0090816.
    1. Mao CP, Bai ZL, Zhang XN, Zhang QJ, Zhang L. Abnormal subcortical brain morphology in patients with knee osteoarthritis: a cross-sectional study. Front Aging Neurosci. 2016;8:3. doi: 10.3389/fnagi.2016.00003.
    1. Mountz JM, Bradley LA, Modell JG, Alexander RW, Triana-Alexander M, Aaron LA, Stewart KE, Alarcón GS, Mountz JD. Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum. 1995 Jul;38(7):926–38.
    1. Oshiro Y, Quevedo AS, McHaffie JG, Kraft RA, Coghill RC. Brain mechanisms supporting spatial discrimination of pain. J Neurosci. 2007 Mar 28;27(13):3388–94. doi: 10.1523/JNEUROSCI.5128-06.2007.
    1. San Pedro EC, Mountz JM, Mountz JD, Liu HG, Katholi CR, Deutsch G. Familial painful restless legs syndrome correlates with pain dependent variation of blood flow to the caudate, thalamus, and anterior cingulate gyrus. J Rheumatol. 1998 Nov;25(11):2270–5.
    1. Wunderlich AP, Klug R, Stuber G, Landwehrmeyer B, Weber F, Freund W. Caudate nucleus and insular activation during a pain suppression paradigm comparing thermal and electrical stimulation. Open Neuroimag J. 2011;5:1–8. doi: 10.2174/1874440001105010001.
    1. Yuan K, Zhao L, Cheng P, Yu D, Zhao L, Dong T, Xing L, Bi Y, Yang X, von Deneen KM, Liang F, Gong Q, Qin W, Tian J. Altered structure and resting-state functional connectivity of the basal ganglia in migraine patients without aura. J Pain. 2013 Aug;14(8):836–44. doi: 10.1016/j.jpain.2013.02.010.
    1. Koyama T, Kato K, Mikami A. During pain-avoidance neurons activated in the macaque anterior cingulate and caudate. Neurosci Lett. 2000 Mar 31;283(1):17–20.
    1. Li BY, Xu T. Influence of morphine microinjected into head of caudate nucleus on electric activities of nociceptive neurons in parafascicular nucleus of rat thalamus. Zhongguo Yao Li Xue Bao. 1990 Mar;11(2):103–7.
    1. Lineberry CG, Vierck CJ. Attenuation of pain reactivity by caudate nucleus stimulation in monkeys. Brain Res. 1975 Nov 7;98(1):119–34.
    1. Mikhaĭlov AV. Responses of caudate nucleus neurons to electrocutaneous stimulation of a paw. Fiziol Zh SSSR Im I M Sechenova. 1980 Sep;66(9):1325–32.
    1. Mulgaonker VK, Mascarenhas JF. Effect of mid-dorsal caudate nucleus on conditioning for pain stimulus in rats. Indian J Physiol Pharmacol. 1991 Jan;35(1):61–4.
    1. Tong ZQ, Chen SC. Effects of stimulation of caudate nucleus on the unit discharges of somato-visceral converging neurons of parafascicular nucleus of thalamus in rats. Sheng Li Xue Bao. 1988 Dec;40(6):586–91.
    1. Tong ZQ, Chen SC, Zhang FT. Effects of stimulation of the rabbit caudate nucleus on units responsive to noxious stimuli in the parafascicular nucleus of the thalamus. Sheng Li Xue Bao. 1985 Apr;37(2):128–36.
    1. Yang F, Lin RJ, Zhou BH, Li P. Effect of lithium applied iontophoretically on electrical activities of pain-related neurons in caudate-putamen nucleus of rat. Sheng Li Xue Bao. 1993 Dec;45(6):519–27.
    1. Yang J, Chen J, Liu W, Song C, Wang C, Lin B. Arginine vasopressin in the caudate nucleus plays an antinociceptive role in the rat. Life Sci. 2006 Oct 26;79(22):2086–90. doi: 10.1016/j.lfs.2006.07.005.
    1. Yang J, Li P, Zhang X, Zhang J, Hao F, Pan Y, Lu G, Lu L, Wang D, Wang G, Yan F. Arginine vasopressin in hypothalamic paraventricular nucleus is transferred to the caudate nucleus to participate in pain modulation. Peptides. 2011 Jan;32(1):71–4. doi: 10.1016/j.peptides.2010.10.014.
    1. Wang D, Yang J, Gu Z, Song C, Liu W, Zhang J, Li X, Li H, Wang G, Song C, Lin B. Arginine vasopressin induces rat caudate nucleus releasing acetylcholine to participate in pain modulation. Peptides. 2010 Apr;31(4):701–5. doi: 10.1016/j.peptides.2009.11.027.
    1. Yang J, Pan Y, Zhao Y, Qiu P, Lu L, Li P, Chen F, Yan X, Wang D. Oxytocin in the rat caudate nucleus influences pain modulation. Peptides. 2011 Oct;32(10):2104–7. doi: 10.1016/j.peptides.2011.08.021.
    1. Keltner JR, Furst A, Fan C, Redfern R, Inglis B, Fields HL. Isolating the modulatory effect of expectation on pain transmission: a functional magnetic resonance imaging study. J Neurosci. 2006 Apr 19;26(16):4437–43. doi: 10.1523/JNEUROSCI.4463-05.2006.
    1. Hansen M, Wetterslev J, Pipper C, Østervig R, Asghar MS, Dahl JB. The area of secondary hyperalgesia following heat stimulation in healthy male volunteers: inter- and intra-individual variance and reproducibility. PLoS One. 2016;11(5):e0155284. doi: 10.1371/journal.pone.0155284.
    1. Davis KD, Moayedi M. Central mechanisms of pain revealed through functional and structural MRI. J Neuroimmune Pharmacol. 2013 Jun;8(3):518–34. doi: 10.1007/s11481-012-9386-8.
    1. Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TE. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage. 2006 Jul 15;31(4):1487–505. doi: 10.1016/j.neuroimage.2006.02.024.
    1. Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, van der Kouwe A, Killiany R, Kennedy D, Klaveness S, Montillo A, Makris N, Rosen B, Dale AM. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron. 2002 Jan 31;33(3):341–55.
    1. Fischl B, Salat DH, van der Kouwe AJ, Makris N, Ségonne F, Quinn BT, Dale AM. Sequence-independent segmentation of magnetic resonance images. Neuroimage. 2004;23 Suppl 1:S69–84. doi: 10.1016/j.neuroimage.2004.07.016.
    1. Fischl B, van der Kouwe A, Destrieux C, Halgren E, Ségonne F, Salat DH, Busa E, Seidman LJ, Goldstein J, Kennedy D, Caviness V, Makris N, Rosen B, Dale AM. Automatically parcellating the human cerebral cortex. Cereb Cortex. 2004 Jan;14(1):11–22.
    1. Abou-Elseoud A, Starck T, Remes J, Nikkinen J, Tervonen O, Kiviniemi V. The effect of model order selection in group PICA. Hum Brain Mapp. 2010 Aug;31(8):1207–16. doi: 10.1002/hbm.20929.
    1. Smith SM, Fox PT, Miller KL, Glahn DC, Fox PM, Mackay CE, Filippini N, Watkins KE, Toro R, Laird AR, Beckmann CF. Correspondence of the brain's functional architecture during activation and rest. Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13040–5. doi: 10.1073/pnas.0905267106.
    1. Hothorn T, Bretz F, Westfall P. Simultaneous inference in general parametric models. Biom J. 2008 Jun;50(3):346–63. doi: 10.1002/bimj.200810425.

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