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Hemodynamic Response to Repeated Noxious Cold Pressor Tests Measured by Functional Near Infrared Spectroscopy on Forehead


The objective of this research was to assess the utility of a simple near infrared spectroscopy (NIRS) technology for objective assessment of the hemodynamic response to acute pain. For this exploration, we used functional near infrared spectroscopy (fNIRS) to measure the hemodynamic response on the forehead during three trials of a cold pressor test (CPT) in 20 adults. To measure hemodynamic changes at the superficial tissues as well as the intracranial tissues, two configurations of ‘far’ and ‘near’ source-detector separations were used. We identified two features that were found to be fairly consistent across all subjects. The first feature was the change of total hemoglobin (THb) concentration in a given condition divided by the duration of that condition \( {\text{THb}}^{\prime} \). Statistical analyses revealed that during the first CPT trial \( {\text{THb}}^{\prime} \) significantly changed from its baseline value in all channels. Also, adaptation to repeated CPTs was observed in both \( {\text{THb}}^{\prime} \) parameter and the reported post-stimulus pain rating scores. The second feature was the difference between the maximum and the minimum of the evoked changes in the THb concentration (ΔTHb). A significant correlation was observed between the post-stimulus pain rating score and ΔTHb at all channels. An asymmetrical activity was observed only at the ‘far’ channels. These results suggest that fNIRS can potentially be used as a reliable technique for the assessment of the hemodynamic response to tonic pain induced by the CPT.

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Confidence interval


Cold pressor test


Cerebrospinal fluid


False discovery rate


Light emitting diode


Functional data analysis


Functional near infrared spectroscopy



HbO2 :



Laterality quotient


Numerical rating scale


Total hemoglobin


  1. Ayaz, H., P. A. Shewokis, A. Curtin, and M. Izzetoglu. Using MazeSuite and functional near infrared spectroscopy to study learning in spatial navigation. J. Vis. Exp. 56(e3443). doi:10.3791/3443, 2011.

  2. Bartocci, M., L. L. Bergqvist, H. Lagercrantz, and K. Anand. Pain activates cortical areas in the preterm newborn brain. Pain 122:109–117, 2006.

    PubMed  Article  Google Scholar 

  3. Becerra, L., W. Harris, M. Grant, E. George, D. Boas, and D. Borsook. Diffuse optical tomography activation in the somatosensory cortex: specific activation by painful vs. non-painful thermal stimuli. PLoS One 4(11):e8016, 2009.

    PubMed  Article  Google Scholar 

  4. Becerra, L., W. Harris, D. Joseph, T. Huppert, D. A. Boas, and D. Borsook. Diffuse optical tomography of pain and tactile stimulation: activation in cortical sensory and emotional systems. NeuroImage 41:252–259, 2008.

    PubMed  Article  CAS  Google Scholar 

  5. Benjamini, Y., and Y. Hochberg. Controlling the false rate discovery: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57(1):289–300, 1995.

    Google Scholar 

  6. Bland, J. M., and D. G. Altman. Calculating correlation coefficients with repeated observations: part 1—correlation within subjects. BMJ 310(6977):446, 1995.

    PubMed  Article  CAS  Google Scholar 

  7. Boynton, G. M., S. A. Engel, G. H. Glover, and D. J. Heeger. Linear systems analysis of functional magnetic resonance imaging in human V1. J. Neurosci. 16(13):4207–4221, 1991.

    Google Scholar 

  8. Bozkurt, A., A. Rosen, H. Rosen, and B. Onaral. A portable near infrared spectroscopy system for bedside monitoring of newborn brain. Biomed. Eng. Online 4(1):29, 2005. doi: 10.1186/1475-925X-4-29.

  9. Bozkurt, A., and B. Onaral. Safety assessment of near infrared light emitting diodes for diffuse optical measurements. Biomed. Eng. Online. 3(9), 2004. doi: 10.1186/1475-925X-3-9

  10. Buckner, R. L. Event-related fMRI and the hemodynamic response. Hum. Brain Mapp. 6:373–377, 1998.

    PubMed  Article  CAS  Google Scholar 

  11. Bunce, S. C., M. Izzetoglu, K. Izzetoglu, B. Onaral, and K. Pourrezaei. Functional near-infrared spectroscopy an emerging neuroimaging modality. IEEE Eng. Med. Biol. 25(4):54–62, 2006.

    Article  Google Scholar 

  12. Casey, K. L., S. Minoshima, T. J. Morrow, and R. A. Koeppe. Comparison of human cerebral activation patterns during cutaneous warmth, heat pain, and deep cold pain. J. Neurophysiol 76(1):571–581, 1996.

    PubMed  CAS  Google Scholar 

  13. Chance, B., E. Anday, S. Nioka, S. Zhou, L. Hong, K. Worden, C. Li, T. Murray, Y. Ovetsky, D. Pidikiti, and R. Thomas. A novel method for fast imaging of brain function, non-invasively, with light. Opt. Express 2(10):411–423, 1998.

    PubMed  Article  CAS  Google Scholar 

  14. Cope, M., D. T. Delpy, E. O. Reynolds, J. Wray, and P. van der Zee. Methods of quantitating cerebral near infrared spectroscopy data. Adv. Exp. Med. Biol. 222:183–189, 1988.

    PubMed  Article  CAS  Google Scholar 

  15. Dehghani, H., and D. T. Delpy. Near-infrared spectroscopy of the adult head: effect of scattering and absorbing obstructions in the cerebrospinal fluid layer on light distribution in the tissue. Appl. Opt. 39(25):4721–4729, 2000.

    PubMed  Article  CAS  Google Scholar 

  16. Devaraj, A. Signal Processing for Functional Near Infrared Neuroimaging. Master’s Thesis, Drexel University. 2005.

  17. Di Piero, V., S. Ferracuti, U. Sabatini, P. Pantano, G. Cruccu, and G. L. Lenzi. A cerebral blood flow study on tonic pain activation in man. Pain 56:167–173, 1994.

    PubMed  Article  Google Scholar 

  18. Downie, W. W., P. A. Leatham, V. M. Rhind, V. Wright, J. A. Branco, and J. A. Anderson. Studies with pain rating scales. Ann. Rheum. Dis. 37:378–381, 1978.

    PubMed  Article  CAS  Google Scholar 

  19. Gélinas, C., M. Choinière, M. Ranger, A. Denault, A. Deschamps, and C. Johnston. Toward a new approach for the detection of pain in adult patients undergoing cardiac surgery: near-infrared spectroscopy—a pilot study. Heart Lung 39(6):485–493, 2010.

    PubMed  Article  Google Scholar 

  20. Grothusen, J. R., and R. J. Schwartzman. Laser Doppler imaging: usefulness in chronic pain medicine. Pain Phys. 15(5):491–498, 2011.

    Google Scholar 

  21. Hines, E. A., and G. E. Brown. A standard stimulus for measuring vasomotor reactions: its application in the study of hypertension. Mayo Clin. Proc. 7:332–335, 1932.

    Google Scholar 

  22. Izzetoglu, M., K. Izzetoglu, S. C. Bunce, H. Ayaz, A. Devaraj, B. Onaral, and K. Pourrezaei. Functional near-infrared neuroimaging. IEEE Trans. Neural Syst. Rehabil. Eng. 13(2):153–159, 2005.

    PubMed  Article  Google Scholar 

  23. Lovallo, W. The cold pressor test and autonomic function: a review and integration. Psychophysiology 12(3):268–282, 1975.

    PubMed  Article  CAS  Google Scholar 

  24. Music, M., Z. Finderle, and K. Cankar. Cold perception and cutaneous microvascular response to local cooling at different cooling temperatures. Microvasc. Res. 81:319–324, 2011.

    PubMed  Article  Google Scholar 

  25. Okada, E., M. Firbank, M. Schweiger, S. R. Arridge, M. Cope, and D. T. Delpy. Theoretical and experimental investigation of near-infrared light propagation in a model of the adult head. Appl. Opt. 36(1):21–31, 1997.

    PubMed  Article  CAS  Google Scholar 

  26. Oldfield, R. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9(1):97–113, 1971.

    PubMed  Article  CAS  Google Scholar 

  27. Panerai, R. B., S. L. Dawson, P. J. Eames, and J. F. Potter. Cerebral blood flow velocity response to induced and spontaneous sudden changes in arterial blood pressure. Am. J. Physiol. Heart Circ. Physiol 280:H2162–H2174, 2001.

    PubMed  CAS  Google Scholar 

  28. Ramsay, J. O., G. Hooker, and S. Graves. Functional Data Analysis with R and MATLAB. Springer, 2009.

  29. Ranger, M., and C. Gélinas. Innovating in pain assessment of the critically ill: exploring cerebral near-infrared spectroscopy as a bedside approach. Pain Manag. Nurs. doi:

  30. Roatta, S., G. Micieli, D. Bosone, G. Losano, R. Bini, A. Cavallini, and P. Magda. Effect of generalised sympathetic activation by cold pressor test on cerebral haemodynamics in healthy humans. J. Auton. Nerv. Syst. 71:159–166, 1998.

    PubMed  Article  CAS  Google Scholar 

  31. Rolfe, P. In vivo near infrared spectroscopy. Annu. Rev. Biomed. Eng. 2:715–754, 2000.

    PubMed  Article  CAS  Google Scholar 

  32. Saager, R., and A. Berger. Measurement of layer-like hemodynamic trends in scalp and cortex: implications for physiological baseline suppression in functional near-infrared spectroscopy. J. Biomed. Opt. 13(3):034017-1–034017-10, 2008.

    Google Scholar 

  33. Seifalian, A. M., G. Stansby, A. Jackson, K. Howell, and G. Hamilton. Comparison of laser Doppler perfusion imaging, laser Doppler flowmetry, and thermographic imaging for assessment of blood flow in human skin. Eur. J. Vasc. Surg. 8(1):65–69, 1994.

    PubMed  Article  CAS  Google Scholar 

  34. Sevick, E. M., C. L. Burch, and B. Chance. Near-infrared optical imaging of tissue phantoms with measurement in the change of optical path lengths. Adv. Exp. Med. Biol. 345:815–823, 1994.

    PubMed  Article  CAS  Google Scholar 

  35. Stancak, Jr., A., A. Yamamotova, I. P. Kulis, and I. V. Sekyra. Cardiovascular adjustments and pain during repeated cold pressor test. Clin. Auton. Res. 6:83–89, 1996.

    PubMed  Article  Google Scholar 

  36. Streff, A., L. K. Kuehl, G. Michaux, and F. Anton. Differential physiological effects during tonic painful hand immersion tests using hot and ice water. Eur. J. Pain 14:266–272, 2010.

    PubMed  Article  Google Scholar 

  37. Swain, I. D., and L. J. Grant. Methods of measuring skin blood flow. Phys. Med. Biol 34(2):151–175, 1989.

    PubMed  Article  CAS  Google Scholar 

  38. Tanida, M., K. Sakatani, R. Takano, and K. Tagai. Relation between asymmetry of prefrontal cortex activities and the autonomic nervous system during a mental arithmetic task: near infrared spectroscopy study. Neurosci. Lett. 369:69–74, 2004.

    PubMed  Article  CAS  Google Scholar 

  39. Villringer, A., and B. Chance. Non-invasive optical spectroscopy and imaging of human brain function. Trends Neurosci. 20:435–442, 1997.

    PubMed  Article  CAS  Google Scholar 

  40. von Baeyer, C. L., T. Piira, C. T. Chambers, M. Trapanotto, and L. K. Zeltzer. Guidelines for the cold pressor task as an experimental pain stimulus for use with children. J. Pain 6(4):218–227, 2005.

    Article  Google Scholar 

  41. Walsh, N. E., L. Schoenfeld, S. Ramamurthy, and J. Hoffman. Normative model for cold pressor test. Am. J. Phys. Med. 68(1):6–11, 1989.

    Article  CAS  Google Scholar 

  42. Washington, L. L., S. J. Gibson, and R. D. Helme. Age-related differences in the endogenous analgesic response to repeated cold water immersion in human volunteers. Pain 89:89–96, 2000.

    PubMed  Article  CAS  Google Scholar 

  43. Watanabe, Y., H. Tanaka, I. Dan, K. Sakurai, K. Kimoto, R. Takashima, and K. Hirata. Monitoring cortical hemodynamic changes after sumatriptan injection during migraine attack by near-infrared spectroscopy. Neurosci. Res. (Shannon, Irel) 69:60–66, 2011.

    CAS  Google Scholar 

  44. Wolf, S., and J. D. Hardy. Studies on pain. Observations on pain due to local cooling and on factors involved in the “cold pressor” effect. J. Clin. Invest. 20(5):521–533, 1941.

    PubMed  Article  CAS  Google Scholar 

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We would like to thank Mr. Frank Kepic for his invaluable technical support and advice. Authors also acknowledge Mr. Troy Carlson for designing and constructing the system for cold pressor tests.

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Correspondence to Kambiz Pourrezaei.

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Associate Editor Jane Grande-Allen oversaw the review of this article.

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Barati, Z., Shewokis, P.A., Izzetoglu, M. et al. Hemodynamic Response to Repeated Noxious Cold Pressor Tests Measured by Functional Near Infrared Spectroscopy on Forehead. Ann Biomed Eng 41, 223–237 (2013).

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  • Numerical rating scale
  • Pain
  • Sympathetic nervous system