title: Modulation of the human nociceptive flexion reflex by pleasant and unpleasant odors.
abstract: The nociceptive withdrawal reflex (NWR), a defensive response that allows withdrawal from a noxious stimulus, is a reliable index of spinal nociception in humans. It has been shown that various kinds of stimuli (emotional, visual, auditory) can modulate the transmission and perception of pain. The aim of the present study was to evaluate, by means of the NWR, the modulatory effect on the spinal circuitry of olfactory stimuli with different emotional valence. The magnitude of the NWR elicited by electrical stimulation of the sural nerve was measured while 18 subjects (9 women, 9 men) smelled pleasant, unpleasant, or neutral odors. The NWR was conditioned by odor probe with interstimulus intervals (ISIs) of 500 ms and 1,500 ms. The magnitude of NWR was significantly greater after the unpleasant odor probe (P <.001) and reduced following the pleasant odor probe (P<.001) at both ISIs. A significant effect of olfactory stimuli on subjective pain ratings were found at both ISIs for pleasant vs unpleasant odors (P<.000), and for both pleasant and unpleasant odors vs neutral and basal conditions (P<.000). No statistical differences in subjective pain ratings at different ISIs were found. Consistent with the notion that NWR magnitude and pain perception can be modulated by stimuli with different emotional valence, these results show that olfactory stimuli, too, can modulate spinal nociception in humans.
authors.affiliation: NeuroRehabilitation Unit, IRCCS Neurological Mediterranean Institute NEUROMED, Pozzilli, Isernia, Italy University Center for Adaptive Disorders and Head pain (UCADH), Pavia, Italy Neurorehabilitation Unit, "Sapienza" University of Rome Polo Pontino, Latina, Italy Rehabilitation Center, Policlinico Italia, Rome, Italy Laboratory of Nociceptive Psychophysiology, Casimiro Mondino National Institute of Neurology Foundation, IRCCS, Pavia, Italy Center of Audiology and Hearing Rehabilitation, Tbilisi, Georgia Tbilisi State Medical University, Tbilisi, Georgia IRCCS Neurological Mediterranean Institute NEUROMED, Pozzilli, Isernia, Italy Fondazione Don Gnocchi, Milan, Italy Headache Science Center, Casimiro Mondino National Institute of Neurology Foundation, IRCCS, Pavia, Italy Department of Public Health, Neuroscience, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Bartolo
authors.forename: Mariano
authors.initials: M
authors.lastname: Serrao
authors.forename: Zurab
authors.initials: Z
authors.lastname: Gamgebeli
authors.forename: Marina
authors.initials: M
authors.lastname: Alpaidze
authors.forename: Armando
authors.initials: A
authors.lastname: Perrotta
authors.forename: Luca
authors.initials: L
authors.lastname: Padua
authors.forename: Francesco
authors.initials: F
authors.lastname: Pierelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nappi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sandrini
mesh_terms: D000328:Adult; D003213:Conditioning, Psychological / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D004644:Emotions / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009812:Odorants; D010146:Pain / Q000517:prevention & control* / Q000523:psychology; D010147:Pain Measurement / Q000379:methods* / Q000523:psychology; D057181:Pleasure / Q000502:physiology; D012903:Smell / Q000502:physiology*; D055815:Young Adult
keywords: Nociception; Nociceptive withdrawal reflex; Odor olfactory stimulation; Olfactory
references.citation: Andersen OK. Studies of the organization of the human nociceptive withdrawal reflex. Focus on sensory convergence and stimulation site dependency. Acta Physiol (Oxf). 2007;189:1-35.
references.citation: Baron RA. Environmentally-induced positive affect: its impact on self-efficacy, task performance, negotiation, and conflict. J Appl Soc Psychol. 1990;20:368-384.
references.citation: Chen D, Haviland-Jones J. Rapid mood change and human odors. Physiol Behav. 1999;68:241-250.
references.citation: Chen D, Haviland-Jones J. Human olfactory communication of emotion. Percept Mot Skills. 2000;91:771-781.
references.citation: Coghill RC, Talbot JD, Evans AC, Meyer E, Gjedde A, Bushnell MC, Duncan GH. Distributed processing of pain and vibration by the human brain. J Neurosci. 1994;14:4095-4108.
references.citation: Craig AD. Pain mechanisms: labeled lines versus convergence in central processing. Annu Rev Neurosci. 2003;26:1-30.
references.citation: Crown ED, King TE, Meagher MW, Grau JW. Shock-induced hyperalgesia: III. Role of the bed nucleus of the stria terminalis and amygdaloid nuclei. Behav Neurosci. 2000;114:561-573.
references.citation: Cruccu G, Anand P, Attal N, Garcia-Larrea L, Haanpää M, Jφrum E, Serra J, Jensen TS. EFNS guidelines on neuropathic pain assessment. Eur J Neurol. 2004;11:153-162.
references.citation: de Wied M, Verbaten MN. Affective pictures processing, attention, and pain tolerance. PAIN®. 2001;90:163-172.
references.citation: Ehrlichman H, Halpern JN. Affect and memory: effects of pleasant and unpleasant odors on retrieval of happy and unhappy memories. J Pers Soc Psychol. 1988;55:769-779.
references.citation: Friedman M. A comparison of alternative tests of significance for the problem of m rankings. Ann Math Stat. 1940;11:86-92.
references.citation: Helmstetter FJ, Bellgowan PS. Lesions of the amygdala block conditional hypoalgesia on the tail flick test. Brain Res. 1993;612:253-257.
references.citation: Herz RS, Engen T. Odor memory: review and analysis. Psychonomic Bull Rev. 1996;3:300-313.
references.citation: Kaviani H, Wilson GD, Checkley SA, Kumari V, Gray JA. Modulation of the human acoustic startle reflex by pleasant and unpleasant odors. J Psychophys. 1998;12:353-361.
references.citation: Lorig TS, Elmes DG, Zald DH, Pardo JV. A computer-controlled olfactometer for fMRI and electrophysiological studies of olfaction. Behav Res Methods Instrum Comput. 1999;31:370-375.
references.citation: Loveless NE, Sanford AJ. Slow potential correlates of preparatory set. Biol Psychol. 1974;1:303-314.
references.citation: Manning BH, Mayer DJ. The central nucleus of the amygdala contributes to the production of morphine antinociception in the rat tail-flick test. J Neurosci. 1995;15:8199-8213.
references.citation: Marchand S, Arsenault P. Odors modulate pain perception: a gender-specific effect. Physiol Behav. 2002;76:251-256.
references.citation: Meagher MW, Arnau RC, Rhudy JL. Pain and emotion: effects of affective picture modulation. Psychosom Med. 2001;63:79-90.
references.citation: Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150:971-979.
references.citation: Mineka S, Henderson RW. Controllability and predictability in acquired motivation. Annu Rev Psychol. 1985;36:495-529.
references.citation: Morgan CD, Covington JW, Geisler MW, Polich J, Murphy C. Olfactory event-related potentials: older males demonstrate the greatest deficits. Electroencephalogr Clin Neurophysiol. 1997;104:351-358.
references.citation: Olofsson JK, Ericsson E, Nordin S. Comparison of chemosensory, auditory and visual event-related potential amplitudes. Scand J Psychol. 2008;49:231-237.
references.citation: Pause BM, Krauel K. Chemosensory event-related potentials (CSERP) as a key to the psychology of odors. Int J Psychophysiol. 2000;36:105-122.
references.citation: Phillips ML, Drevets WC, Rauch SL, Lane R. Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biol Psychiatry. 2003;54:504-514.
references.citation: Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science. 2000;288:1769-1772.
references.citation: Rainville P. Brain mechanisms of pain affect and pain modulation. Curr Opin Neurobiol. 2002;12:195-204.
references.citation: Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC. Pain affect encoded in human anterior cingulated but not somatosensory cortex. Science. 1997;277:968-971.
references.citation: Rhudy JL, Meagher MW. The role of emotion in pain modulation. Curr Opin Psychiatry. 2001;14:241-245.
references.citation: Rhudy JL, Williams AE, McCabe KM, Rambo PL, Russell JL. Emotional modulation of spinal nociception and pain: the impact of predictable noxious stimulation. PAIN®. 2006;126:221-233.
references.citation: Rhudy JL, France CR, Bartley EJ, McCabe KM, Williams AE. Psychophysiological responses to pain: further validation of the nociceptive flexion reflex (NFR) as a measure of nociception using multilevel modeling. Psychophysiology. 2009;46:939-948.
references.citation: Rhudy JL, Bartley EJ, Williams AE. Habituation, sensitization, and emotional valence modulation of pain responses. PAIN®. 2010;148:320-327.
references.citation: Rotton J, Barry T, Frey J, Soler E. Air pollution and interpersonal attraction. J Appl Soc Psychol. 1978;8:57-71.
references.citation: Roy M, Pichè M, Chen JI, Peretz I, Rainville P. Cerebral and spinal modulation of pain by emotions. Proc Natl Acad Sci U S A. 2009;106:20900-20905.
references.citation: Royet JP, Koenig O, Gregoire MC, Cinotti L, Lavenne F, Le Bars D, Costes N, Vigouroux M, Farget V, Sicard G, Holley A, Mauguiere F, Comar D, Froment JC. Functional anatomy of perceptual and semantic processing for odors. J Cognit Neurosci. 1999;11:94-109.
references.citation: Sandrini G, Serrao M, Rossi P, Romaniello A, Cruccu G, Willer JC. The lower limb flexion reflex in humans. Prog Neurobiol. 2005;77:353-395.
references.citation: Tassorelli C, Sandrini G, Proietti-Cecchini A, Nappi RE, Sances G, Martignoni E. Changes in nocicpetive flexion reflex threshold across the menstrual cycle in healthy women. Psychosom Med. 2002;64:621-626.
references.citation: Thesen T, Murphy C. Age-related changes in olfactory processing detected with olfactory event-related brain potentials using velopharyngeal closure and natural breathing. Int J Psychophysiol. 2001;40:119-127.
references.citation: Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron. 2007;55:377-391.
references.citation: Villemure C, Bushnell MC. Cognitive modulation of pain: how do attention and emotion influence pain processing? PAIN®. 2002;95:195-199.
references.citation: Villemure C, Bushnell MC. Mood influences supraspinal pain processing separately from attention. J Neurosci. 2009;29:705-715.
references.citation: Villemure C, Slotnick BM, Bushnell MC. Effects of odors on pain perception: deciphering the roles of emotion and attention. PAIN®. 2003;106:101-108.
references.citation: Villemure C, Wassimi S, Bennett GJ, Shir Y, Bushnell MC. Unpleasant odors increase pain processing in a patient with neuropathic pain: psychophysical and fMRI investigation. PAIN®. 2006;120:213-220.
references.citation: Weisenberg M, Raz T, Hener T. The influence of film-induced mood on pain perception. PAIN®. 1998;76:365-375.
references.citation: Willer JC, Boureau F, Albe-Fessard D. Supraspinal influences on nociceptive flexion reflex and pain sensation in man. Brain Res. 1979;179:61-68.
references.citation: Zald DH, Pardo JV. Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation. Proc Natl Acad Sci USA. 1997;94:4119-4124.
references.citation: Zelman DC, Howland EW, Nichols SN, Cleeland CS. The effects of induced mood on laboratory pain. PAIN®. 1991;46:105-111.