Advertisement

Methodological Considerations for the Temporal Summation of Second Pain

Published:August 08, 2017DOI:https://doi.org/10.1016/j.jpain.2017.07.009

      Highlights

      • The study provides a comparison of temporal summation stimulation techniques.
      • Results suggest constant contact ramping protocols underestimate temporal summation.
      • Models using temporal summation should consider intermittent tapping techniques.

      Abstract

      Temporal summation of second pain (TSSP) is a psychophysical indication of a central pain encoding mechanism, potentially enhanced in pathological pain conditions. Low-frequency repetitive stimulation of unmyelinated (C) nociceptors results in a progressive increase of pain intensity when thermal stimulation intensity remains constant. However, when using different methods of nociceptive delivery to the skin, regularity as well as rate of pain enhancement with repetition varies between experiments. Specifically, repetitive ramping up and down from a neutral to a painful temperature has produced weak and inconsistent pain summation. In contrast, repetitive contact of the skin with a preheated probe has generated substantial pain summation. In the present study, TSSP by the intermittent contact with a preheated thermode and constant contact, ramp and hold methods were compared during 10 iterations of stimulation of glabrous skin of the hand or hairy forearm skin, with an onset to onset interval of 3.3 seconds and stimulus interval of .8 seconds. Significantly greater TSSP was observed for intermittent contact stimulation at both sites (P < .001). Differential activation of myelinated and unmyelinated nociceptors by ramping and tapping may account for different rates of temporal summation of heat pain.

      Perspective

      This article presents direct evidence suggesting the constant contact, ramp and hold stimulus may underestimate the level of TSSP. This evidence suggests the re-evaluation of stimulation techniques used for temporal summation tests, especially within clinical models.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Anderson R.J.
        • Craggs J.G.
        • Bialosky J.E.
        • Bishop M.D.
        • George S.Z.
        • Staud R.
        • Robinson M.E.
        Temporal summation of second pain: Variability in responses to a fixed protocol.
        Eur J Pain. 2013; 17: 67-74
        • Coderre T.J.
        • Katz J.
        • Vaccarino A.L.
        • Melzack R.
        Contribution of central neuroplasticity to pathological pain: Review of clinical and experimental evidence.
        Pain. 1993; 52: 259-285
        • Dickenson A.H.
        • Sullivan A.F.
        Evidence for a role of the NMDA receptor in the frequency dependent potentiation of deep rat dorsal horn nociceptive neurones following c fibre stimulation.
        Neuropharmacology. 1987; 26: 1235-1238
        • Eckert N.
        • Cruz-Almeida Y.
        • Riley J.
        Influence of testing modality on ratings of first and second pain in humans.
        J Pain. 2015; 16: S22
        • Eckert N.R.
        • Vierck C.J.
        • Simon C.B.
        • Cruz-Almeida Y.
        • Fillingim R.B.
        • Riley III, J.L.
        Testing assumptions in human pain models: Psychophysical differences between first and second pain.
        J Pain. 2017; 18: 266-273
        • Eide P.K.
        Wind-up and the NMDA receptor complex from a clinical perspective.
        Eur J Pain. 2000; 4: 5-15
        • Geisser M.E.
        A closer look at temporal summation of second pain in healthy persons.
        Eur J Pain. 2013; 17: 3-4
        • Goodin B.R.
        • Bulls H.W.
        • Herbert M.S.
        • Schmidt J.
        • King C.D.
        • Glover T.L.
        • Sotolongo A.
        • Sibille K.T.
        • Cruz-Almeida Y.
        • Staud R.
        Temporal summation of pain as a prospective predictor of clinical pain severity in adults aged 45 years and above with knee osteoarthritis: Ethnic differences.
        Psychosom Med. 2014; 76: 302-310
        • Granot M.
        • Granovsky Y.
        • Sprecher E.
        • Nir R.R.
        • Yarnitsky D.
        Contact heat-evoked temporal summation: Tonic versus repetitive-phasic stimulation.
        Pain. 2006; 122: 295-305
        • Granot M.
        • Sprecher E.
        • Yarnitsky D.
        Psychophysics of phasic and tonic heat pain stimuli by quantitative sensory testing in healthy subjects.
        Eur J Pain. 2003; 7: 139-143
        • Herrero J.F.
        • Laird J.M.
        • Lopez-Garcia J.A.
        Wind-up of spinal cord neurones and pain sensation: Much ado about something?.
        Prog Neurobiol. 2000; 61: 169-203
        • Iannetti G.D.
        • Zambreanu L.
        • Tracey I.
        Similar nociceptive afferents mediate psychophysical and electrophysiological responses to heat stimulation of glabrous and hairy skin in humans.
        J Physiol. 2006; 577: 235-248
        • Janal M.N.
        • Raphael K.G.
        • Cook D.B.
        • Sirois D.A.
        • Nemelivsky L.
        • Staud R.
        Thermal temporal summation and decay of after-sensations in temporomandibular myofascial pain patients with and without comorbid fibromyalgia.
        J Pain Res. 2016; 9: 641
        • Johansson R.S.
        • Vallbo Å.B.
        Tactile sensibility in the human hand: Relative and absolute densities of four types of mechanoreceptive units in glabrous skin.
        J Physiol. 1979; 286: 283-300
        • Kenshalo D.R.
        • Anton F.
        • Dubner R.
        The detection and perceived intensity of noxious thermal stimuli in monkey and in human.
        J Neurophysiol. 1989; 62: 429-436
        • Kong J.T.
        • Johnson K.A.
        • Balise R.R.
        • Mackey S.
        Test-retest reliability of thermal temporal summation using an individualized protocol.
        J Pain. 2013; 14: 79-88
        • Li J.
        • Simone D.A.
        • Larson A.A.
        Windup leads to characteristics of central sensitization.
        Pain. 1999; 79: 75-82
        • Liu X.G.
        • Morton C.R.
        • Azkue J.J.
        • Zimmermann M.
        • Sandkühler J.
        Long-term depression of C-fibre-evoked spinal field potentials by stimulation of primary afferent Aδ-fibres in the adult rat.
        Eur J Neurosci. 1998; 10: 3069-3075
        • Lundberg L.E.
        • Jørum E.
        • Holm E.
        • Torebjörk H.E.
        Intra-neural electrical stimulation of cutaneous nociceptive fibres in humans: Effects of different pulse patterns on magnitude of pain.
        Acta Physiol Scand. 1992; 146: 41-48
        • Mauderli A.P.
        • Vierck C.J.
        • Cannon R.L.
        • Rodrigues A.
        • Shen C.
        Relationships between skin temperature and temporal summation of heat and cold pain.
        J Neurophysiol. 2003; 90: 100-109
        • McGlone F.
        • Olausson H.
        • Boyle J.A.
        • Jones-Gotman M.
        • Dancer C.
        • Guest S.
        • Essick G.
        Touching and feeling: Differences in pleasant touch processing between glabrous and hairy skin in humans.
        Eur J Neurosci. 2012; 35: 1782-1788
        • Naugle K.M.
        • Cruz-Almeida Y.
        • Fillingim R.B.
        • Staud R.
        • Riley J.L.
        Novel method for assessing age-related differences in the temporal summation of pain.
        J Pain Res. 2016; 9: 195-205
        • Naugle K.M.
        • Cruz-Almeida Y.
        • Fillingim R.B.
        • Staud R.
        • Riley III, J.L.
        Increased spatial dimensions of repetitive heat and cold stimuli in older women.
        Pain. 2017; 158: 973-979
        • Nielsen J.
        • Arendt-Nielsen L.
        The importance of stimulus configuration for temporal summation of first and second pain to repeated heat stimuli.
        Eur J Pain. 1998; 2: 329-341
        • Price D.D.
        Characteristics of second pain and flexion reflexes indicative of prolonged central summation.
        Exp Neurol. 1972; 37: 371-387
        • Price D.D.
        • Dubner R.
        Mechanisms of first and second pain in the peripheral and central nervous systems.
        J Invest Dermatol. 1977; 69: 167-171
        • Price D.D.
        • Hu J.W.
        • Dubner R.
        • Gracely R.H.
        Peripheral suppression of first pain and central summation of second pain evoked by noxious heat pulses.
        Pain. 1977; 3: 57-68
        • Price D.D.
        • Mao J.
        • Frenk H.
        • Mayer D.J.
        The N-methyl-d-aspartate receptor antagonist dextromethorphan selectively reduces temporal summation of second pain in man.
        Pain. 1994; 59: 165-174
        • Price D.D.
        • McGrath P.A.
        • Rafii A.
        • Buckingham B.
        The validation of visual analogue scales as ratio scale measures for chronic and experimental pain.
        Pain. 1983; 17: 45-56
        • Price D.D.
        • Staud R.
        • Robinson M.E.
        • Mauderli A.P.
        • Cannon R.
        • Vierck C.J.
        Enhanced temporal summation of second pain and its central modulation in fibromyalgia patients.
        Pain. 2002; 99: 49-59
        • Raphael K.G.
        • Janal M.N.
        • Ananthan S.
        • Cook D.B.
        • Staud R.
        Temporal summation of heat pain in temporomandibular disorder patients.
        J Orofac Pain. 2009; 23: 54-64
        • Riley J.L.
        • Cruz-Almeida Y.
        • Glover T.L.
        • King C.D.
        • Goodin B.R.
        • Sibille K.T.
        • Bartley E.J.
        • Herbert M.S.
        • Sotolongo A.
        • Fessler B.J.
        Age and race effects on pain sensitivity and modulation among middle-aged and older adults.
        J Pain. 2014; 15: 272-282
        • Sjölund B.H.
        Peripheral nerve stimulation suppression of C-fiber-evoked flexion reflex in rats: Part 1: Parameters of continuous stimulation.
        J Neurosurg. 1985; 63: 612-616
        • Staud R.
        • Cannon R.C.
        • Mauderli A.P.
        • Robinson M.E.
        • Price D.D.
        • Vierck Jr., C.J.
        Temporal summation of pain from mechanical stimulation of muscle tissue in normal controls and subjects with fibromyalgia syndrome.
        Pain. 2003; 102: 87-95
        • Staud R.
        • Robinson M.E.
        • Price D.D.
        Temporal summation of second pain and its maintenance are useful for characterizing widespread central sensitization of fibromyalgia patients.
        J Pain. 2007; 8: 893-901
        • Staud R.
        • Vierck C.J.
        • Cannon R.L.
        • Mauderli A.P.
        • Price D.D.
        Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome.
        Pain. 2001; 91: 165-175
        • Staud R.
        • Vierck C.J.
        • Robinson M.E.
        • Price D.D.
        Effects of the N-methyl-D-aspartate receptor antagonist dextromethorphan on temporal summation of pain are similar in fibromyalgia patients and normal control subjects.
        J Pain. 2005; 6: 323-332
        • Staud R.
        • Weyl E.E.
        • Riley III, J.L.
        • Fillingim R.B.
        Slow temporal summation of pain for assessment of central pain sensitivity and clinical pain of fibromyalgia patients.
        PLoS One. 2014; 9: e89086
        • Treede R.D.
        • Meyer R.A.
        • Campbell J.N.
        Myelinated mechanically insensitive afferents from monkey hairy skin: Heat-response properties.
        J Neurophysiol. 1998; 80: 1082-1093
        • Treede R.D.
        • Meyer R.A.
        • Raja S.N.
        • Campbell J.N.
        Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin.
        J Physiol. 1995; 483: 747-758
        • Vierck Jr., C.J.
        Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia).
        Pain. 2006; 124: 242-263
        • Vierck C.J.
        • Cannon R.L.
        • Fry G.
        • Maixner W.
        • Whitsel B.L.
        Characteristics of temporal summation of second pain sensations elicited by brief contact of glabrous skin by a preheated thermode.
        J Neurophysiol. 1997; 78: 992-1002
        • Vierck C.J.
        • Mauderli A.P.
        • Riley III, J.L.
        Relationships between the intensity and duration of Peltier heat stimulation and pain magnitude.
        Exp Brain Res. 2013; 225: 339-348
        • Vierck C.J.
        • Whitsel B.L.
        • Favorov O.V.
        • Brown A.W.
        • Tommerdahl M.
        Role of primary somatosensory cortex in the coding of pain.
        Pain. 2013; 154: 334-344
        • Woolf C.J.
        • Thompson S.W.
        The induction and maintenance of central sensitization is dependent on N-methyl-d-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states.
        Pain. 1991; 44: 293-299
        • Yeomans D.C.
        • Proudfit H.K.
        Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat: Electrophysiological evidence.
        Pain. 1996; 68: 141-150
        • Zachariou V.
        • Goldstein B.D.
        • Yeomans D.C.
        Low but not high rate noxious radiant skin heating evokes a capsaicin-sensitive increase in spinal cord dorsal horn release of substance P.
        Brain Res. 1997; 752: 143-150